Faculty Participants
The 91女神 Institute for Drug and Biotherapeutic Innovation brings together talented faculty from a variety of disciplines across 91女神. The faculty currently participating in the program can be found below.
Leadership
Molecular Microbiology and Immunology
The Tavis lab鈥檚 primary focus is antiviral drug discovery targeting the Hepatitis B Virus ribonuclease H (RNaseH). The lab has developed a suite of biochemical and cell-based assays to evaluate how inhibitors of the RNaseH affect the enzyme and viral replication. Its key resource is a small but chemically diverse set of nuclease inhibitors and their analogs. The lab routinely conducts cytotoxicity assays using MTS (mitochondrial function), neutral red retention (lysosome function), crystal violet retention (DNA accumulation, usually interpreted as cell growth), and LDH release (plasma membrane integrity) to gain a more comprehensive view of how its compound affect the cell. The lab collaborates with medicinal chemists in the United States, France, Greece and China and is actively pushing forward two anti-HBV RNaseH hit-to-lead optimization projects. They work closely with other members of the 91女神-IDBI, including Feng Cao, Ph.D.; Maureen Donlin, Ph.D.; Lynda Morrison, Ph.D.; and Getahun Abate, Ph.D. Through these collaborations, the lab has demonstrated that the inhibitors in its library can have high selectivity for one virus or cellular organism over the others, opening a pathway to antimicrobial development targeting nucleases.
The research in Marvin Meyers' lab is focused on the application of medicinal chemistry toward the discovery of potential drug candidates to treat people with rare and neglected diseases. It collaborates with experts in infectious disease biology, including malaria, tuberculosis, infectious diarrhea (cryptosporidiosis), cryptococcal meningitis, hepatitis B virus and herpes simplex virus. The lab also has ongoing collaborations with experts in oncology, FSHD muscular dystrophy and infant short-gut syndrome.
The lab uses synthetic organic chemistry techniques to prepare new compounds, which are analyzed by its collaborators to assess their biological properties. Using medicinal chemistry and structure-based drug design principles, the lab optimizes the potency, pharmacokinetics and safety profiles of compounds with the goals of the identification of tool compounds and, ultimately, candidate drug molecules for clinical trials.
Biomedical Engineering
Silviya Zustiak鈥檚 laboratory focuses on hydrogel biomaterials and soft tissue engineering, with emphasis on developing novel biomaterials as cell scaffolds, drug screening platforms and protein delivery devices. 3D biomaterial-based models are crucial for closing the reproducibility gap between 2D tissue culture and animal models by providing a cell environment that mimics real tissue. 3D systems could have an immediate impact in the development of platforms for toxicology screening, addressing concerns of drug failures in clinical trials due to lack of efficacy or unforeseen side effects. The laboratory also develops injectable and biodegradable hydrogels for sustained localized drug and protein delivery. This research is highly multidisciplinary, merging engineering, materials science, and biology.
Biochemistry and Molecular Biology
Fran Sverdrup's lab is focused on drug discovery in human genetic and infectious diseases. They perform target identification and validation, drug screening and preclinical evaluation of drug candidates. Their major project targets facioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of muscular dystrophy for which there is no treatment. They have identified druggable pathways that modulate expression of the toxic DUX4 gene responsible for FSHD and are translating those finding into potential therapies. They are currently advancing three exciting classes of drugs, identified through high-throughput screening, that turn off DUX4 expression. This includes a robust lead optimization program involving close collaboration with their medicinal chemistry colleagues. Svedrup is moving these compounds into animal model testing and have established a key collaboration with a pharmaceutical partner to eventually advance into human clinical trials. A second interest is in anti-infectives research with recent programs targeting malaria, lymphatic filariasis and African sleeping sickness. To accomplish these activities, Sverdrup maintains a network of collaborations with disease experts, medicinal chemists, pharmaceutical/biotech companies and foundations. Fran Sverdrup is also the Director of the IDBI Discovery Services Core, including ADMEPK and LC/MS services.
Biology
blythe.janowiakmulligan@slu.edu;
Blythe Janowiak studies the opportunistic pathogen Group B Streptococcus. While present in the normal human vaginal microbiota, pregnant mothers are routinely screened and treated with broad spectrum antibiotics to lower risks to immune-na茂ve newborns. This has unintended consequences for later development of a newborns healthy microbiome, leading to increased inflammation, asthma, and immune-disorder risk. Janowiak studies the interaction between GBS, the microbiome, and the healthy or altered immune system, and regulation of glutathione synthesis and metabolism as a means to reveal novel, specific and selective treatments for GBS. Janowiak also collaborates throughout the university, providing expert guidance on tools and strategies for studying the microbiome, oxidative stress, and antioxidants in multiple systems. Finally, Janowiak has a strong passion in training the future generation of biomedical scientists, as evidenced by her mentoring 5-10 undergrads and 1-3 grad students in biochemical and microbiological research per semester.
Pharmacology and Physiology
john.walker@health.slu.edu; Website;
Research in the Walker lab focuses mainly on synthetic and medicinal chemistry to develop tool compounds or novel therapeutic agents against a variety of biological targets and therapeutic indications. The lab is actively involved in multiple research collaborations partnering with investigators both at 91女神 and other Universities. They use modern synthesis techniques and also a number of in silico approaches to design and synthesize new target molecules.
A major area of research focus and collaboration for their group is developing strategies and molecules to target antibacterial resistance as part of their long-standing collaboration with the Zgurskaya and Rybenkov labs at the University of Oklahoma. They are working to develop molecules that can penetrate the outer membrane of Gram-negative pathogens and inhibit efflux pumps, which contribute both to the intrinsic and acquired resistance of many pathogens to antibiotics. They recently demonstrated that novel ligands they prepared can potentiate the activity of the antibiotics novobiocin and erythromycin in E. coli.
Infectious Disease
Infectious Diseases
The development of new drugs against mycobacterial diseases is one of Getahun Abate鈥檚 key research interests. His lab works closely with the Hoft lab, and has the following capacities: screening new drugs against bacillus Calmitte Guerin (the attenuated TB vaccine) using a rapid growth inhibition assay, testing drugs on reference strains of Mycobacterium tuberculosis and M. avium, studying anti-mycobacterial activities against intracellular mycobacteria using human macrophages from healthy donors, testing interactions of new drugs with first-line anti-TB drugs against extracellular and intracellular mycobacteria, studying the effects of new drugs on mycobacterium-specific immunity and testing the cytotoxicity of new drugs on THP-1 (human) and J774.A1 (murine) macrophage cell lines. His lab also has a protocol to test the anti-TB activities of new drugs in murine TB model.
Biochemistry and Molecular Biology
maureen.donlin@health.slu.edu;
Maureen Donlin's lab is interested in developing new anti-fungal drugs, with an immediate focus on compounds that can inhibit Cryptococcus neoformans, a pathogen affecting immune-suppressed patients. She is a bioinformatician with extensive experience in biochemistry, molecular genetics, biostatistics and computer programming who has provided bioinformatics and biostatistical support to the Departments of Biochemistry and Microbiology at 91女神 for 17 years. She is well versed in the SPSS statistical package, and programming skills include PERL, MySQL, PHP, HTML and the statistical language R. She has conducted the primary analysis of microarray, RNAseq and proteomics data from several difference species in collaboration with many different groups. She is applying these skills to identify the target(s) of the highly effective inhibitors of C. neoformans that she has identified through her screening efforts. Donlin is also the director of the 91女神 master鈥檚 program in bioinformatics and computational biology and can help identify potential interns for higher order data analysis needs of the 91女神-IDBI and partners.
Molecular Microbiology and Immunology
lynda.morrison@health.slu.edu;
The Morrison lab focuses primarily on developing new chemotherapy for herpes simplex viruses, and possibly other herpesviruses. The lab has identified several new chemotypes with anti-herpes activity from among compounds in the Tavis lab compound library. They have the capacity to screen compounds in a higher throughput 96-well format (colorimetric or luminescence assay), assess genome load by qPCR and inhibition of virus replication by plaque assay. Cytotoxicity of compounds is routinely assessed by MTS, LDH and neutral red assays. Its collaborators carry out biochemical assays for inhibition of enzymatic activity. In addition, they are adept with mouse models of HSV-1 eye disease, HSV-1/HSV-2 genital disease (vaginal mucosa), and are developing a mouse model of HSV-1 skin infection.
Molecular Microbiology and Immunology
The Tavis lab鈥檚 primary focus is antiviral drug discovery targeting the Hepatitis B Virus ribonuclease H (RNaseH). The lab has developed a suite of biochemical and cell-based assays to evaluate how inhibitors of the RNaseH affect the enzyme and viral replication. Its key resource is a small but chemically diverse set of nuclease inhibitors and their analogs. The lab routinely conducts cytotoxicity assays using MTS (mitochondrial function), neutral red retention (lysosome function), crystal violet retention (DNA accumulation, usually interpreted as cell growth), and LDH release (plasma membrane integrity) to gain a more comprehensive view of how its compound affect the cell. The lab collaborates with medicinal chemists in the United States, France, Greece and China and are actively pushing forward two anti-HBV RNaseH hit-to-lead optimization projects. They work closely with other members of the 91女神-IDBI, including Feng Cao, Ph.D.; Maureen Donlin, Ph.D.; Lynda Morrison, Ph.D.; and Getahun Abate, Ph.D. Through these collaborations, the lab has demonstrated that the inhibitors in its library can have high selectivity for one virus or cellular organism over the others, opening a pathway to antimicrobial development targeting nucleases.
Infectious Diseases, Internal Medicine
daniel.hoft@health.slu.edu; Center for Vaccine Development Website
Daniel Hoft is the Chief of the 91女神 Division of Infectious Diseases, Allergy and Immunology, and Director of the 91女神 Center for Vaccine Development. Hoft studies the immune response to multiple intracellular pathogens including Mycobacterium tuberculosis and Trypanosoma cruzi, and works collaboratively to develop and support studies for new drugs against these pathogens.. He has also contributed extensively to the development of multiple vaccines including generating 91女神-held IP for a universal flu vaccine, and development of a multi-omics core for studying vaccine responses. Hoft leads the extended stay research unit of the vaccine center, allowing for vaccine-challenge studies against flu and many other pathogens.
Clinical Microbiology, Medical Molecular Microbiology, 91女神 Hospital
robin.chamberland@health.slu.edu;
Robin Chamberland, Ph.D., directs the clinical microbiology labs at SSM Saint Louis University Hospital. She assists 91女神-DDG investigators who may need access to clinical samples and provides clinical perspective to 91女神-DDG investigators. Chamberland studies antimicrobial resistance in S. aureus, a relatively common commensal bacterium that causes opportunistic infections with growing drug resistance. She also studies bacterial toxins and their interaction with the host innate immune system. She focuses on the setting of S. aureus necrotizing pneumonia.
Biology
laurie.shornick@slu.edu; Website
Laurie Shornick's research explores the neonatal immune response to respiratory viral infection, and how the developing immune system is functionally different from those of adults. Shornick also studies the immune factors in maternal milk and how they may modulate the neonatal immune response. Other projects within Shornick鈥檚 group study immune cell activation during the course of normal and diabetic wound healing, and ways to improve diabetic wound healing to prevent amputation and improve wound co-morbidities.
Chemistry, Pharmacology and Physiology
The research in Marvin Meyers' lab is focused the application of medicinal chemistry towards the discovery of potential drug candidates to treat people with rare and neglected diseases. It collaborates with experts in infectious disease biology, including malaria, tuberculosis, infectious diarrhea (cryptosporidiosis), cryptococcal meningitis, hepatitis B virus and herpes simplex virus. The lab also has ongoing collaborations with experts in oncology, FSHD muscular dystrophy and infant short-gut syndrome.
The lab uses synthetic organic chemistry techniques to prepare new compounds, which are analyzed by its collaborators to assess their biological properties. Using medicinal chemistry and structure-based drug design principles, the lab optimizes the potency, pharmacokinetics and safety profiles of compounds with the goals of identification of tool compounds and, ultimately, candidate drug molecules for clinical trials.
Biology
blythe.janowiakmulligan@slu.edu;
Blythe Janowiak, Ph.D., studies the opportunistic pathogen Group B Streptococcus. While present in the normal human vaginal microbiota, pregnant mothers are routinely screened and treated with broad-spectrum antibiotics to lower risks to immune-na茂ve newborns. This has unintended consequences for the later development of a newborn's healthy microbiome, leading to increased inflammation, asthma, and immune-disorder risk. Janowiak studies the interaction between GBS, the microbiome, and the healthy or altered immune system, and the regulation of glutathione synthesis and metabolism as a means to reveal novel, specific and selective treatments for GBS. Janowiak also collaborates throughout the university, providing expert guidance on tools and strategies for studying the microbiome, oxidative stress, and antioxidants in multiple systems. Finally, Janowiak has a strong passion in training the future generation of biomedical scientists, as evidenced by her mentoring 5-10 undergrads and 1-3 grad students in biochemical and microbiological research per semester.
Molecular Microbiology and Immunology
Karoly Toth鈥檚 primary focus is the testing of anti-adenoviral drugs, and other anti-virals. Toth's expertise is in vivo drug testing; they developed the Syrian hamster model to study human adenovirus infections. Syrian hamsters (unlike mice and rats) are permissive for human adenoviruses, and develop pathology similar to that in humans. They use this model to evaluate the therapies against disseminated and respiratory adenovirus infection. Toth also develops Syrian hamster models for other viruses, including enteric norovirus and SARS-CoV-2. Over the past several years, Toth has conducted over 60 studies with 17 drug candidates as a contractor to the NIH Animal Models for Infectious Disease program, forming collaborations with academic and industrial laboratories in the USA and Europe.
Clinical Health Sciences
rita.heuertz@health.slu.edu; Website
Rita Heuertz, Ph.D., studies the production, maintenance, and antibiotic resistance of bacterial biofilms and biofilm-associated infections, which account for more than 80% of microbial infections. Specific roles of bioactive compounds and components of the innate immune response have not been elucidated for bacteria in the context of biofilm and remain incomplete and poorly understood. Heuertz's research is defining the roles and mechanisms of anti-biofilm responses in fighting biofilm-associated infections. She also has a particular interest in the identification and characterization of phytochemicals with anti-biofilm activity.
Molecular Microbiology and Immunology
Ann Tollefson's research focuses on the development of adenoviral vectors as gene therapy and anti-cancer agents, as well as the study of adenovirus infection, treatment, and prevention. She works extensively with Karoly Toth on collaborative projects around adenovirus and other viral vectors and animal model development.
Institute for Molecular Virology, Molecular Microbiology and Immunology
duane.grandgenett@health.slu.edu;
Duane Grandgenett's laboratory has been studying retroviruses since 1970 and discovered the viral integrase (IN) in 1978 in avian retroviruses. IN is responsible for integration of the viral DNA into the host chromosomes. Since the early 1990s, they have focused on HIV-1 IN and helped Merck & Co develop the first major lead inhibitors directed against IN. The first FDA-approved inhibitor, Raltegravir, was in 2007. Two other companies are marketing similar active site inhibitors, one of which (Dolutegravir, GSK) is far superior at the clinical level. Their current efforts are directed towards understanding the mechanisms associated with the assembly of HIV-1 and Rouse Sarcoma Virus (RSV) IN-DNA complexes and their analyses at atomic-resolution level. There are no HIV-1 IN-DNA complexes where detailed active site inhibitors can be thoroughly evaluated, except though a very distantly related surrogate prototype foamy virus IN-DNA model. They are now investigating whether the RSV IN-DNA complex can be utilized to study HIV-1 inhibitors at the atomic level. Their recent publications strongly suggest that RSV IN will serve as an excellent surrogate model for HIV-1 IN inhibitors. RSV and HIV-1 IN are similar genetically and structurally and, are equally inhibited in vivo and in vitro by the HIV-1 clinical inhibitors.
Chair, Department of Chemistry
The Demchenko laboratory, Glycoworld, has trained more than 150 researchers and has developed many innovative tools for the synthesis and application of carbohydrates (glycans or glycoconjugates) in five major areas:
- New synthetic reagents and building blocks;
- Reactions for stereocontrolled glycosylation;
- Expeditious strategies and automated technologies for oligosaccharide synthesis;
- Biomedical studies on the development of glycopharmaceuticals; and
- Integration of glycans and nanomaterials in carbohydrate nanotechnology.
Some of these methods have been applied to the synthesis of tumor-associated glycosphingolipids to study their roles in metastasis of cancers and in pathogenesis of neurodegenerative diseases; glycoconjugates of important bacterial pathogens Streptococcus pneumoniae and Staphylococcus aureus for vaccine development; glycopeptides as LPS antagonists for treating septicemia and for the development of Alzheimer's disease therapeutics; human milk oligosaccharides to study their functions, and carbohydrate-based imaging reagents, enzyme inhibitors, and personalized vaccine adjuvants.
Molecular Microbiology and Immunology
The Tse lab focuses its research on virology, particularly coronavirus, dengue virus, and adeno-associated virus. Virology is one of the most exciting fields in biology, from the on-going COVID-19 pandemic to viral-based gene and cancer therapies. In the Tse Lab, we seek to understand viral pathogenesis and transmission (zoonotic, enzootic and pandemic) at the molecular level to inform and develop new guidelines, vaccines, and antivirals for public health. In addition, we engineer pathogenic viruses into harmless nanoparticles for use in gene therapy and vaccine development.
Evolution is the best engineer in nature. Inspired by the elegance of evolution, we use multiple innovative technologies, including saturation-mutagenesis, directed-evolution, molecular engineering, CRISPR genome-wide screening, and multiple鈥搊mics sequencing, to recapitulate, direct, and accelerate the natural evolutionary process in a controlled laboratory environment. These methods are used to:
1) Dissect each facet of viral infection and improve our understanding of viral pathogenesis
and transmission, and
2) Convert such knowledge to engineer viruses into novel nanoparticles for medical
uses.
Internal Medicine - Infectious Disease
The Liu laboratory studies gene regulation and immune responses during chronic inflammation, with a particular interest in identifying the roles of RNA-binding proteins (RBPs) in the regulation of immune evasion during Mycobacterium tuberculosis (Mtb) infection and breast cancer development. Liu is investigating how RBPs regulate cytokine expression and the effects on pathogen-specific T cell development. In addition, the Liu lab is identifying targets for host-directed therapy and undertaking drug screening campaigns against tuberculosis, especially with drug-resistant Mtb.
Internal Medicine - Infectious Disease
Brett Jagger, Ph.D., conducts clinical trials at 91女神's Center for Vaccine Development (CVD), including studies initiated through the NIAID Vaccine and Treatment Evaluation Unit (VTEU) network. He is trained in molecular virology as well as pre-clinical vaccine development, and is interested in developing antiviral as well as immunomodulatory therapeutics for arboviral and respiratory viral pathogens, especially encephalitic arboviruses and influenza. His goal is to advance therapeutics for these viral diseases across the continuum of drug development, from in silico screens, through validation in laboratory and animal model systems, and ultimately, human clinical trials. He is also interested in the development of Controlled Human Infection Models (CHIMs) to advance the prevention and treatment of rare and emerging diseases, hosted at 91女神's Extended Stay Research Unit.
Molecular Microbiology and Immunology
Krishan Pandey, Ph.D., studies the mechanisms of retroviral integration and determinants of viral integrase inhibitor drug resistance. Using the model Rous Sarcoma Virus (RSV) and cryo-EM, Pandey explores the structure of the intasome, determining the structural components responsible for DNA binding, inhibitor binding, and the interactions leading to intasome inhibition. Pandey is extending these studies of the RSV intasome to that of HIV-1 and HIV-2, studying intasome assembly in these viruses to design novel or improved integrase inhibitors for the treatment of HIV.
Molecular Microbiology and Immunology
nathan.ungerleider@health.slu.edu;
The Ungerleider ab studies the Epstein Barr Virus, a tumor-associated pathogen that has established a lifelong infection in nearly the entire world鈥檚 population. EBV promotes the long-term survival and proliferation of host cells and is a causal factor in a number of lymphomas and epithelial cancers. Their work explores how EBV replicates, how infection drives tumorigenesis, and seeks to identify targetable vulnerabilities in EBV-associated cancers.
Rare, Orphan and Genetic Diseases
Pediatrics
adriana.montano@health.slu.edu;
Adriana Monta帽o is an expert in the study and development of therapies for mucopolysaccharidosis (MPS), a set of rare diseases affecting bone, musculoskeletal and organ development. Her discoveries include potential therapies for MPS IVA. Her work is extensive, working on multiple facets Morquio disease. She has contributed to the development of clinical repositories, enabling discovery and diagnostic research, improvement of diagnostic and childhood screening protocols and assays, as well as extensive research improving enzyme replacement therapy by protein and delivery optimization. Monta帽o has also collaborated with multiple industry partners to study other lysosomal storage and bone disorders.
Biochemistry and Molecular Biology
Fran Sverdrup's lab is focused on drug discovery in human genetic and infectious diseases. They perform target identification and validation, drug screening and preclinical evaluation of drug candidates. Their major project targets facioscapulohumeral muscular dystrophy (FSHD), one of the most common forms of muscular dystrophy for which there is no treatment. They have identified druggable pathways that modulate expression of the toxic DUX4 gene responsible for FSHD and are translating those findings into potential therapies. They are currently advancing three exciting classes of drugs, identified through high-throughput screening, that turn off DUX4 expression. This includes a robust lead optimization program involving close collaboration with their medicinal chemistry colleagues. Sverdrup is moving these compounds into animal model testing and have established a key collaboration with a pharmaceutical partner to eventually advance into human clinical trials. A second interest is in anti-infectives research with recent programs targeting malaria, lymphatic filariasis and African sleeping sickness. To accomplish these activities, Sverdrup maintains a network of collaborations with disease experts, medicinal chemists, pharmaceutical/biotech companies and foundations.
Molecular Microbiology and Immunology
Rajeev Aurora, Ph.D., studies mechanisms that lead to chronic inflammation in the context of osteoimmunology, osteoarthritis, and bone degeneration. His lab uses mouse models and human studies, employing computational and laboratory tools to understand the genetic, epigenetic, and environmental factors that lead from acute inflammation to chronic activation of the immune system. The Aurora laboratory has developed a treatment that promotes the crosstalk between the immune and skeletal systems to restore homeostasis. It has been recognized that cytokines produced by proinflammatory T-cells leads to activation of osteoclasts, cells that resorb bone. Persistent exposure to the cytokines leads to erosion of the bone in several diseases including postmenopausal osteoporosis, rheumatoid arthritis and periodontitis. The laboratory discovered that osteoclasts, in addition to their bone resorbing activity also are antigen presenting cells. He holds multiple patents on treatments for bone degeneration diseases.
Internal Medicine, Geriatric Medicine
Andy Nguyen, Ph.D., studies how deficiencies in progranulin, a protein linked to frontotemporal dementia (FTD), causes neurodegeneration. He is actively pursuing development of strategies to increase progranulin levels as potential therapies for progranulin deficient FTD. Nguyen is also investigating progranulin鈥檚 structure and function using a variety of molecular and cellular approaches.
Biochemistry
sergey.korolev@health.slu.edu;
The Sergey Korolev lab studies mechanism of protein function using X-ray crystallography combined with biophysical and biochemical methods. Systems of interest include 1) recombination mediator proteins (RMPs) important for genome maintenance, DNA repair and implicated in cancer (BRCA1/2, PALB2) and pathogen drug resistance; 2) DNA helicases involved in DNA replication and repair; 3) calcium-independent phospholipase (iPLA2B) critical for inflammation, calcium homeostasis and implicated in a wide spectrum of diseases from ischemia to neurodegeneration.
Biochemistry and Molecular Biology
susana.gonzalohervas@health.slu.edu;
Susana Gonzalo's long-term research interest is to understand the molecular mechanisms that contribute to the genomic instability that drives aging and cancer, with the ultimate goal of targeting these mechanisms therapeutically. Nuclear lamins orchestrate genome organization, forming a scaffold for tethering chromatin and protein complexes regulating many nuclear functions. Lamin dysfunction impacts nuclear architecture, chromatin structure, as well as DNA transcription, replication and repair. These data, and the association of lamins dysfunction with dozen of degenerative disorders, premature aging, and cancer, provide evidence for these proteins operating as 鈥渃aretakers of the genome." Gonzalo's research focuses on identifying mechanisms whereby lamins regulate genome stability and function, as these mechanisms are key to identify therapies that ameliorate the progression of laminopathies in patients.
Biology
judith.ogilvie@slu.edu; Website
A major focus of the Ogilvie lab is on retinal degenerative diseases. They have a well-characterized in vitro mouse model of early onset retinitis pigmentosa using the rd1 mouse retina grown in organ culture for four weeks. This system allows for environmental and drug manipulations. In addition, they are currently collaborating with Nader Sheibani at University of Wisconsin to develop and characterize a rapid onset mouse model of diabetic retinopathy. Research progress on this disease has been slowed by the very gradual onset and development of symptoms in animal models that are currently available. Previous work has included an intravitreal gene-therapy approach to treatment of retinal and brain degeneration due to inherited mucopolysaccharidosis defects.
Biology
Sofia Origanti, Ph.D., studies the regulation of protein synthesis with a focus on eukaryotic initiation factors (eIFs). Many eIFs are overexpressed in cancers and serve to enhance cancer growth. eIF6 is one such factor that is overexpressed in many types of cancers and serves as a potential therapeutic target for inhibiting cancer growth and progression. eIF6 is also deregulated in the rare disorder Shwachman-Diamond syndrome (SDS) and targeting eIF6 has been proposed as a potential therapeutic mechanism for treating SDS.Pediatrics, Biochemistry and Molecular Biology
Jeffrey Teckman, M.D., is chair of the Department of Pediatrics, and a practicing pediatric gastroenterologist. Teckman is a world authority in the metabolic disease alpha-1-antitrypsin deficiency, is published and recognized in other liver diseases, and is an experienced consultant to industry and has been involved in FDA applications. His 25 years of academic research have involved molecular biology, cell biology, protein trafficking, and rare diseases focused on liver injury, genetic-metabolic disease, and liver therapeutics. Teckman also has 20 years of experience in continuously funded clinical research, including industry trials phases 1, 2 and 3, multi-center natural history studies and international database trials.
Metabolic Diseases
Pharmacology and Physiology
Gina Yosten, Ph.D., has developed novel screening methods to match formerly 鈥榦rphan鈥� G-protein coupled receptors (GPCRs) to their cognate ligands, an important step in identifying their role in biologic and disease processes. She is using these findings to study the role of GPCRs in diabetes-associated microvascular dysfunction and in central circuits underlying obesity-associated hypertension.Biochemistry and Molecular Biology
Kyle McCommis, Ph.D., is an expert in the role of mitochondrial metabolism in health and disease. One project studies the connection between heart failure and altered hepatic metabolism via liver ketone body production. Another project studies mitochondrial metabolism during the activation of hepatic stellate cells and their role in liver fibrosis. A third studies mitochondrial metabolism and its relationship to obesity and diabetes. Kyle has a particular interest in the role of the mitochondrial pyruvate carrier in these systems and is engaged on projects to understand the MPC structure and function in depth. This research may lead to treatments reducing hepatic fibrosis through inhibition of mitochondrial metabolism.
Biology
judith.ogilvie@slu.edu; Website
A major focus of the Ogilvie lab is on retinal degenerative diseases. They have a well-characterized in vitro mouse model of early onset retinitis pigmentosa using the rd1 mouse retina grown in organ culture for four weeks. This system allows for environmental and drug manipulations. In addition, they are currently collaborating with Nader Sheibani at University of Wisconsin to develop and characterize a rapid onset mouse model of diabetic retinopathy. Research progress on this disease has been slowed by the very gradual onset and development of symptoms in animal models that are currently available. Previous work has included an intravitreal gene therapy approach to treatment of retinal and brain degeneration due to inherited mucopolysaccharidosis defects.
Biology
Laurie Shornick's research explores the neonatal immune response to respiratory viral infection, and how the developing immune system is functionally different from those of adults. Shornick also studies the immune factors in maternal milk and how they may modulate the neonatal immune response. Other projects within Shornick鈥檚 group study immune cell activation during the course of normal and diabetic wound healing, and ways to improve diabetic wound healing to prevent amputation and improve wound co-morbidities.Pharmacology and Physiology
anutosh.chakraborty@health.slu.edu; Website
Obesity and obesity-associated metabolic dysfunction cause various co-morbidities such as type 2 diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease, non-alcoholic fatty liver disease, reproductive dysfunction, respiratory abnormalities, psychiatric conditions, and certain types of cancer. A combination of lifestyle modification, dietary alterations and pharmacology is necessary to combat obesity. Yet, attempts to ameliorate obesity, especially in the long term, have not been successful. One reason is that a complete knowledge of how metabolic organs function is lacking as all the metabolic components have not yet been identified.
The Chakraborty laboratory focuses to determine the functions of novel proteins or pathways in metabolism. The goal is to develop drugs that ameliorate metabolic diseases by modulating these targets. With the help of Institute- and NIH-funded grants, the group discovered that the inositol pyrophosphate biosynthetic enzyme IP6K1 is a potential target in metabolic diseases such as obesity, type-2 diabetes, and non-alcoholic fatty liver disease. The team determined the mechanisms by which IP6K1 promotes metabolic dysfunction. Moreover, they demonstrated that targeting this pathway is a pharmacologically viable approach to treat metabolic diseases. Currently, The Chakraborty lab aims to address two of the important issues in IP6K1 research. 1) The mechanisms that regulate IP6K1 in vivo have not yet been identified. They discovered a novel protein that regulates IP6K1 in vivo. 2) The available IP6K1 inhibitor compound is a pan-IP6K inhibitor, and it does not possess drug-like properties. Therefore, the group tests in vivo efficacy of the newly developed IP6K inhibitor compounds, developed by various collaborators.
Published genome-wide association, transcriptomic and proteomic studies together with the lab鈥檚 ongoing studies identified many novel proteins that regulate metabolism. The long-term goal of the Chakraborty laboratory is to elucidate functions of these proteins in health and diseases.
Pharmacology and Physiology
vincenza.cifarelli@health.slu.edu
Vincenza Cifarelli has developed a multidisciplinary research program that addresses the role of vascular and lymphatic endothelium in tissue homeostasis and remodeling, inflammation and metabolic health. Area of interests are gut-liver axis, adipose tissue disfunction in metabolic disease and cardiac inflammation. The Cifarelli Lab conducts studies in rodent model of disease as well as in people with genetic variants in the lipid transporter CD36.
Pediatric Gastroenterology, Pediatrics
Ajay Jain鈥檚 research interests include pediatric liver and gut diseases and nutrition. The Jain lab evaluates strategies targeting liver and gut injury noted in short bowel syndrome (SBS), which results from bowel resection or lack of functional gut. SBS patients require intravenous nutrition through a process called Total Parenteral Nutrition (TPN). Despite being a lifesaver, complications in SBS include life-threatening and potentially fatal, intestinal failure associated liver disease (IFALD) as well as gut injury with gut mucosal atrophy and increase gut permeability. The lab studies many aspects of SBS and nutrition, including the role of gut microbiota in TPN-associated injury, and markers of nutritional status and injury. Jain lab is currently evaluating novel molecules in mitigating injury associated with SBS, under a $1.9 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
Jain is the director of the M.D./Ph.D. program at 91女神 School of Medicine, and medical director of the pediatric liver transplant program at SSM Health Cardinal Glennon Children鈥檚 Hospital.
Biology
daniel.warren@slu.edu; Website
Daniel Warren's research program centers on understanding how animals are able to meet the physiological challenges imposed by their environments and by their natural and evolutionary histories. He uses an integrative approach to understand why some animals, particularly pond turtles, are better able to tolerate dramatic changes in oxygen availability, temperature and body-fluid pH. At the cellular level, his studies focus on the heart, which must and does continue to function under conditions (low oxygen and extremely low pH) that would otherwise be fatal to other vertebrates, including mammals. These include studies of cardiac pH regulation and the effects of pH on the cellular processes involved in excitation-contraction coupling, the sequence of events that starts with electrical depolarization of the cell and culminates in mechanical shortening. Warren aims to improve the understanding of how these processes evolved throughout evolution and to better characterize new or existing solutions to physiological problems that many kinds of organisms face. Warren's work may also lead to the identification of targets for therapeutic intervention to treat human diseases associated with inborn errors in metabolism and ischemia, a pathological condition that occurs most notably in the heart and brain when blood flow (and, therefore, oxygen and glucose delivery) is restricted during myocardial infarction and stroke, respectively.
Chemistry
premila.russell@slu.edu; Website
Research in the Samuel Russell Lab centers on applying computational chemistry methods to build and simulate atomistic models of human cell environments. Using these "cells-on-computers", they aim to address the current challenges in characterizing "hidden states" of biomolecules within the complex cell environments that arise from limitations of spatial-temporal resolutions of traditional experiments and in silico methods. Characterizing biophysical properties, especially at the atomic level, of such biomolecular states can lead to health advances. Samuel Russell's long-term focus is to combine these cells-on-computers technology with complementary experimental approaches to develop streamlined platforms for both investigating structural mechanisms of cell-specific human diseases and screening drugs in a rapid and cost-effective manner. Current focuses of projects in their research program include mechanisms of red blood cell diseases, which can lead to cardiovascular complications, and metabolic pathways in cancer cells.
Neuropathy and Pain
Chair, Department of Pharmacology and Physiology
Director, Institute for Translational Neuroscience
Fellow, Academy of Science of St. Louis
Fellow, National Academy of Inventors
daniela.salvemini@health.slu.edu; Website
Daniela Salvemini is the William Beaumont Professor and chair of the Department of Pharmacology and Physiology, and the director of the Institute for Translational Neuroscience. Salvemini focuses her work on discovery and development of therapeutics for non-opioid pain relief. Using multi-disciplinary approaches including genetic, molecular, and pharmacological tools, her lab studies how neuro-inflammatory processes impact periphery and CNS during chronic pain. Her discoveries in adenosine A3 receptor signaling pathway have been licensed to BioIntervene, which she helped found. Salvemini is a Fellow of themAcademy of Science of St. Louis, and a Fellow of the National Academy of Inventors.
Chemistry
Chris Arnatt utilizes organic and synthetic chemistry to generate targeted small molecules for research on cellular processes, disease states, and therapy. He has a special interest in developing chemical and fluorescent probes to study biologic systems, and focuses his research on nuclear proteins and DNA modifications in cancer and stem cell biology. Much of their current research is focused on deciphering the protein-ligand interactions of the G Protein-Coupled Estrogen Receptor (GPER, GPR30). Through collaborations with biologists, pharmacologists, and geneticists at 91女神 and the Albert Einstein School of Medicine, they have begun to reveal that GPER plays a role in neurological development and gallstone formation.
Internal Medicine, Geriatric Medicine
Andy Nguyen, Ph.D., studies how deficiencies in progranulin, a protein linked to frontotemporal dementia (FTD), causes neurodegeneration. He is actively pursuing the development of strategies to increase progranulin levels as potential therapies for progranulin-deficient FTD. Nguyen is also investigating progranulin鈥檚 structure and function using a variety of molecular and cellular approaches.
Biochemistry
sergey.korolev@health.slu.edu;The Korolev lab studies mechanism of protein function using X-ray crystallography combined with biophysical and biochemical methods. Systems of interest include 1) recombination mediator proteins (RMPs) important for genome maintenance, DNA repair and implicated in cancer (BRCA1/2, PALB2) and pathogen drug resistance; 2) DNA helicases involved in DNA replication and repair; 3) calcium-independent phospholipase (iPLA2B) critical for inflammation, calcium homeostasis and implicated in a wide spectrum of diseases from ischemia to neurodegeneration.
Pharmacology and Physiology
gina.yosten@health.slu.edu; Website
Gina Yosten has developed novel screening methods to match formerly 鈥榦rphan鈥� G-protein coupled receptors (GPCRs) to their cognate ligands, an important step in identifying their role in biologic and disease processes. She is using these findings to study the role of GPCRs in diabetes-associated microvascular dysfunction and in central circuits underlying obesity-associated hypertension.
Biology
The Xu lab seeks to help optimize drugs that promote nervous system development and neural regeneration by investigating their physiological roles and cellular mechanisms, as well as evaluating their potential neurotoxicity. To do this, the lab utilizes multiple state-of-the-art approaches. These include in vitro cell culture of primary neurons, PC-12 cells, and HEK 293 cells, electrophysiology, calcium imaging, immunocytochemistry, confocal microscopy, pharmacological and molecular biological techniques. Currently, the Xu lab is actively collaborating with Arnatt (91女神 Chemistry) to develop specific and effective agonists and antagonists for G-protein coupled estrogen receptors (GPER) and investigate the physiology role and the underlying mechanisms of GPER in neural growth and synapse formation. The lab is also collaborating with Zustiak (91女神 Biomedical engineering) and Kuljanishvili (91女神 Physics) to develop 3D nanoparticle-hydrogel composites for nerve repair
Pharmacology and Physiology
Research in the Moutal group aims to discover mechanisms driving the transition from physiological (protective) to pathological (chronic) pain. Chronic pain is a devastating neurological disorder affecting nearly 20% of the global population, with a profound negative impact on quality of life and life expectancy. To improve the translational potential of pre-clinical research, the lab uses reverse translation of rare painful clinical syndromes as a guide to aid in the discovery of novel therapeutic targets. The group has filed 4 provisional patents on novel targets for chronic pain treatment and a novel therapeutic approach for migraine.
Moutal's current NIH-funded program investigates a subset of rare autoimmune diseases, painful paraneoplastic encephalitis, as a gateway to discover new determinants of physiological and chronic pain. His focus is on molecular mechanisms causing chronic pain in patients who develop autoimmunity against Collapsin Response Mediator Protein 5 (CRMP5). His approach is to reverse translate these clinical findings to characterize the mechanism by which the target of autoantibodies, CRMP5, can participate in chronic neuropathic pain. The lab applies multiple biochemical and genetic approaches and expertise in techniques such as live cell microscopy, electrophysiology, protein biochemistry and cutting-edge approaches including micro-electrode array recording, CRISPR/Cas9 gene editing, proteomic analyses, peptide mapping, and single cell western blot.
Pharmacology and Physiology
liberty.francoismoutal@health.slu.edu
Liberty Fran莽ois-Moutal focuses on studying the synaptic delivery of mRNA in neurodegeneration and painful neuropathies. With her expertise in biochemistry, biophysical characterization of protein interactions with biologically active molecules, as well as drug design approaches, she aims to characterize and target interactions relevant to RNA transport.
Biochemistry
Yuna Ayala investigates the cellular function and molecular structure of RNA binding proteins to understand basic mechanisms of RNA processing and pathogenesis. Her work focuses on on the TARD DNA binding protein (TDP-43), an essential RNA binding protein whose dysfunction and aggregation are closely associated with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), frontotemporal lobar degeneration (FTLD) and Alzheimers. Ayala's work includes the study of TDP-43 aggregation, function and loss of function, and techniques to inhibit aggregation and restore protein function.
Biology
mohini.sengupta@slu.edu; Website
The Sengupta Lab is interested in deciphering how different muscles are coordinated for diverse movements, how this coordination is refined over development and how this coordination is disrupted in motor diseases. Generating movement is essential for survival. Even simple movements like walking require precise coordination between different body parts that is not a trivial feat. Just like toddlers slowly get better at walking, motor coordination improves as the animal matures. Motor coordination is specifically disrupted in several motor diseases and spinal cord injury, yet therapy remains limited.
In vertebrates, neurons in the spinal cord help generate movements and are modulated by inputs from the brain. The Sengupta lab use zebrafish, a tiny, transparent vertebrate to study motor coordination. Spinal neurons in zebrafish are homologous to other vertebrates like mice and humans but are significantly less in number and complexity providing a tractable system to investigate motor control. Moreover, the transparency at early stages allows easy use of in vivo techniques to record from neurons (electrophysiology, calcium imaging) and manipulate them (optogenetics) during natural behaviors (swimming, hunting). Using these techniques, the Sengupta Lab aims to determine how zebrafish coordinate their fins and body during swimming and how this coordination develops. By defining functions of distinct populations in the brain and spinal cord, we aim to provide tangible targets for much needed therapy.
Cardiovascular, Liver and Other Organ Systems
Biochemistry and Molecular Biology
Kyle McCommis is an expert in the role of mitochondrial metabolism in health and disease. One project studies the connection between heart failure and altered hepatic metabolism via liver ketone body production. Another project studies mitochondrial metabolism during activation of hepatic stellate cells and their role in liver fibrosis. A third studies mitochondrial metabolism and it鈥檚 relationship to obesity and diabetes. Kyle has a particular interest in the role of the mitochondrial pyruvate carrier in these systems and is engaged on projects to understand the MPC structure and function in depth. This research may lead to treatments reducing hepatic fibrosis through inhibition of mitochondrial metabolism.
Biochemistry and Molecular Biology
The 脕ngel Bald谩n laboratory is interested in sterol homeostasis and in the molecular mechanisms involved in the conversion of macrophages into foam cells. This latter process is particularly relevant in several human pathologies, including atherosclerosis and different pulmonary lipidosis syndromes.
Biochemistry and Molecular Biology
Yie-Hwa Chang has been developing anti-cancer drugs and antibiotics for the past 15 years. His lab discovered and characterized two types of methionine aminopeptidases (MetAPs). The type-2 MetAP plays a key role in angiogenesis, and has been identified as a potential target for developing anti-cancer and anti-obesity drugs. The lab's discovery was licensed to 11 major pharmaceutical companies for their drug discovery projects. Chang worked with David Griggs and Eric Jacobsen to identify promising MetAP inhibitors as potential anti-TB drugs. In collaboration with Tomasz Heyduk, Chang developed a series of novel homogeneous assays used by many pharmaceutical companies for high-throughput drug screening projects. For example, they developed the first homogeneous assay for cAMP, S-adenosylmethionine (SAMe) and L-tryptophan.
Biochemistry and Molecular Biology
David Ford has pioneered the field of lipidomics to study mechanisms responsible for cardiovascular diseases. He combines expertise in physiological models of diseases with mass spectrometry and bio-organic techniques to interrogate alterations in lipid metabolism and signaling pathways involved with cardiovascular disease. Ford also applies these lipidomics techniques to collaborator studies including infectious diseases and vaccines. Ford is the director of the Center for Cardiovascular Research.
Molecular Microbiology and Immunology
The Tavis lab鈥檚 primary focus ins antiviral drug discovery targeting the Hepatitis B Virus ribonuclease H (RNaseH). The lab has developed a suite of biochemical and cell-based assays to evaluate how inhibitors of the RNaseH affect the enzyme and viral replication. Its key resource is a small but chemically diverse set of nuclease inhibitors and their analogs. The lab routinely conducts cytotoxicity assays using MTS (mitochondrial function), neutral red retention (lysosome function), crystal violet retention (DNA accumulation, usually interpreted as cell growth), and LDH release (plasma membrane integrity) to gain a more comprehensive view of how its compound affect the cell. The lab collaborates with medicinal chemists in the United States, France, Greece and China and are actively pushing forward two anti-HBV RNaseH hit-to-lead optimization projects. They work closely with other members of the 91女神-IDBI, including Feng Cao, Ph.D.; Maureen Donlin, Ph.D.; Lynda Morrison, Ph.D.; and Getahun Abate, Ph.D. Through these collaborations, the lab has demonstrated that the inhibitors in its library can have high selectivity for one virus or cellular organism over the others, opening a pathway to antimicrobial development targeting nucleases.
Biochemistry and Molecular Biology
Pathological activation of the complement and clotting cascades leads to thrombosis and chronic inflammation and is linked to the onset and progression of autoimmune disorders. Nicola Pozzi鈥檚 laboratory studies the unknown biology of complement and clotting factors, investigate their structure-function relationships, identify new ligands and define their mechanisms of recognition. Finally, they engineer novel constructs to correct the disease state. His current work focuses on the structures of proteins involved in antiphospholipid syndrome (APS), as well as the role of protein disulfide isomerases in thrombosis, cancer, and neurodegeneration. The recent development of a novel family of anticoagulant fusion proteins to ameliorate the outcome of patients suffering from thrombosis in acute clinical settings such as sepsis and stroke is an example of their work.Chemistry
Research in the Scott Martin group is focused on the development and use of microfluidic devices to study cell-to-cell communication. This includes the use of 3D printing as well as traditional microfabrication procedures to design devices that integrate three-dimensional cell culture with analytical detection schemes. These devices are being used to create realistic in vitro models of in vivo systems. A major project is the development of microfluidic devices to devices containing cells cultured on ECM scaffolds coupled with online analytical assays to quantitatively study cell-cell interactions. They are utilizing these devices to study endothelial-macrophage interactions during inflammatory and healing atherosclerotic phenotypes. Other projects include the development of a microchip-based blood-brain barrier (BBB) mimic to study the effect of nitric oxide (NO) on the integrity of the BBB; microchip-based analysis/reactor system to study the effect of NO on the onset of Parkinson's disease; and new microchip and electrochemical materials to enable the detection of NO release from endothelial cells.
Internal Medicine, Gastroenterology; 91女神 Liver Center
Brent Tetri is an international expert on non-alcoholic fatty liver disease (NASH/NFLD), studying mechanisms of disease formation, progression, and therapeutics. He has developed widely used animal models of NASH, as well as models, methods and assays to study pancreatitis. Tetri is regularly called upon to provide expert consultation to industry on pre-clinical studies, clinical study design, and clinical study endpoint selection in the liver and pancreatic diseases.
Pediatrics, Biochemistry and Molecular Biology
Jeffrey Teckman is chair of the Department of Pediatrics, and a practicing pediatric gastroenterologist. Teckman is a world authority in the metabolic disease alpha-1-antitrypsin deficiency, is published and recognized in other liver diseases, and is an experienced consultant to industry and has been involved in FDA applications. His 25 years of academic research have involved molecular biology, cell biology, protein trafficking, and rare diseases focused on liver injury, genetic-metabolic disease, and liver therapeutics. Teckman also has 20 years of experience in continuously funded clinical research, including industry trials phases 1, 2 and 3, multi-center natural history studies and international database trials.Pharmacology and Physiology
Mark Knuepfer researches the role of the autonomic nervous system in health and disease. Specifically, Knuepfer is studying the role of afferent nerves in the pathology and physiology of hypertension and cardiac failure. His lab is exploring hemodynamic responses to acute stress and drug toxicity, and genetic causes of response variability.Pharmacology and Physiology
Willis Samson is an internationally known expert on the hypothalamic (neuropeptide) control of metabolism, cardiovascular function and appetitive behaviors. Samson鈥檚 long term research goal is to understand the function of active peptides in the brain, and potentially targeting these peptides for therapeutic use in eating disorders and prevention of fatal hypoglycemia in insulin-dependent diabetics. Using pancreatic and CNS tissue models, they also engage in work to match orphan G protein coupled receptors to their endogenous ligands.Pharmacology and Physiology
vincenza.cifarelli@health.slu.edu
Vincenza Cifarelli has developed a multidisciplinary research program that addresses the role of vascular and lymphatic endothelium in tissue homeostasis and remodeling, inflammation and metabolic health. Area of interests are gut-liver axis, adipose tissue disfunction in metabolic disease and cardiac inflammation. The Cifarelli Lab conducts studies in rodent model of disease as well as in people with genetic variants in the lipid transporter CD36.
Biology
daniel.warren@slu.edu; Website
Daniel Warren's research program centers on understanding how animals are able to meet the physiological challenges imposed by their environments and by their natural and evolutionary histories. He uses an integrative approach to understand why some animals, particularly pond turtles, are better able to tolerate dramatic changes in oxygen availability, temperature and body-fluid pH. At the cellular level, his studies focus on the heart, which must and does continue to function under conditions (low oxygen and extremely low pH) that would otherwise be fatal to other vertebrates, including mammals. These include studies of cardiac pH regulation and the effects of pH on the cellular processes involved in excitation-contraction coupling, the sequence of events that starts with electrical depolarization of the cell and culminates in mechanical shortening. Warren aims to improve the understanding of how these processes evolved throughout evolution and to better characterize new or existing solutions to physiological problems that many kinds of organisms face. Warren's work may also lead to the identification of targets for therapeutic intervention to treat human diseases associated with inborn errors in metabolism and ischemia, a pathological condition that occurs most notably in the heart and brain when blood flow (and, therefore, oxygen and glucose delivery) is restricted during myocardial infarction and stroke, respectively.
Internal Medicine - Gastreoenterology
Xiaofeng Fan's researches liver diseases and liver-diease causing infections by combination of molecular techniques, next-generation sequencing and bioinformatics. He utilizes several techniques, including long RT-PCR (patented) and template-dependent multiple displacement amplification that enable the study of human genomics and infection at the single-cell level and within body fluids. Research in his lab is also exploring connections between biomarkers of liver disease within easily accessible bodily fluids, and the progression of disease within the liver.
Biomaterials and Nanomaterials
Chemistry
Dana Baum鈥檚 research focuses on the identification of functional nucleic acids (FNAs), such aptamers and DNAzymes, for use in a variety of practical applications. In addition to studies investigating ability of FNAs to participate in redox processes, we are developing FNAs with molecular recognition abilities that can be applied to sensors, biomolecule organization, and biomolecule delivery.Chemistry
Steven Buckner鈥檚 group develops and tests novel nanomaterials and nanocomposites for a variety of applications including propulsion, hydrogen generation, imaging, and biomedical applications. Buckner has collaborated with many IDBI members for the development of novel materials for fine vasculature imaging, energetic materials, and materials to enhance tissue and bone formation.
Biomedical Engineering
Natasha Case conducts research in orthopaedic bioengineering, emphasizing articular cartilage and bone. Her research focuses on how mechanical, biophysical, and biochemical stimuli interact to direct cartilage tissue development and adaptation, applied to optimizing tissue engineering strategies. Case aims to expand knowledge about structure-function relationships in orthopaedic tissues and to increase understanding about biophysical regulation of these tissues, with the long-term goal of applying knowledge in these areas to enhance repair strategies for orthopaedic tissues.Biomedical Engineering
Koyal Garg鈥檚 research is focused on developing lamin-based biomaterial and stem cell therapies for improving the regeneration and functional capacity of skeletal muscle following injury, disease or aging. These studies extend to the role of inflammation in muscle repair and damage, and methods to prevent fibrosis after injury. Garg has developed clinically relevant mouse and rat models of VML (with or without an adjacent bone fracture). Using these models, they are studying the efficacy of extracellular matrix (ECM) based materials, mesenchymal stem cell spheroids and exosomes, and electrically stimulated eccentric contractions for treatment of VML injury. The lab is equipped to perform immune-histological as well as gene and protein expression analysis. They also assess in vivo peak isometric torque and eccentric force.Biomedical Engineering
Scott Sell conducts research on tissue engineering and regenerative medicine, focusing on the use of electrospinning to create extracellular matrix analogue scaffolds for dermal and musculoskeletal repair. He has also done extensive research on the incorporation and controlled release of platelet-rich plasma from electrospun scaffolds.Biomedical Engineering
Silviya Zustiak鈥檚 laboratory focuses on hydrogel biomaterials and soft tissue engineering, with emphasis on developing novel biomaterials as cell scaffolds, drug screening platforms and protein delivery devices. 3D Biomaterial-based models are crucial for closing the reproducibility gap between 2D tissue culture and animal models by providing a cell environment that mimics real tissue. 3D systems could have an immediate impact in the development of platforms for toxicology screening, addressing concerns of drug failures in clinical trials due to lack of efficacy or unforeseen side effects. The laboratory also develops injectable and biodegradable hydrogels for sustained localized drug and protein delivery. This research is highly multidisciplinary, merging engineering, materials science and biology.Biomedical Engineering; Center for Additive Manufacturing
Andrew Hall has primary research interest on the intersection of medical imaging and medical devices. His research includes projects on image guided surgical interventions, such as guided robotic surgery and improvements in the localization and functionality of surgical robotics, particularly in pedicle screw placement and laminectomy in the spine. He is also interested in the use of 3D printing and 3D scanning in medicine. Hall collaborates on many projects with other 91女神 researchers on radiology, nanoparticles, and cancer therapy. Hall is also the Co-Founder and Director of the 91女神 Center for Additive Manufacturing, and applies his extensive industry experience to tackling competitive problems in health care.Physics
Irma Kuljanishvili performs research on the synthesis and characterization of novel 1D and 2D nanoscale materials for scalable device technologies and applications. This work includes development of novel Scanning Probe Microscopy and Spectroscopy techniques, as well as SPM based lithography and Nanoscale design, assembly, and patterning techniques. She collaborates with other 91女神-IDBI researchers on the development of new solid-state materials that can be combined in with biological molecules to create composites with new properties or multiple targets. Her interests also include functionalization of materials for use in medical devices, or for use as anti-bacterial or direct anti-cancer agents.Chemistry
Paul Jelliss has research interests that span the field of inorganic chemistry including metal-based nanomaterials for use in energetics and medical applications as well as organometallic chemistry, looking at transition metal complexes that incorporate boron for possible pharmacological or biotechnological uses. His areas of work include: reactive metal nanomaterials and synthesis for energetics applications, development of nanocomposite rocket propellants, designing metallocarborane complexes for drug delivery, and study of metallocarborane photophysical and electrochemical properties.Department of Health Sciences, Nursing and Public Health; 91女神-Madrid
Anya Hillery鈥檚 research has focused on drug delivery systems, drug targeting, and liposomes. She has also studied and published on synthetic peptide vaccines and oral drug delivery. Hillery is a member of the faculty at 91女神 鈥� Madrid (Spain).Biomedical Engineering
alex.j.reiter@slu.edu; Website
Alex Reiter鈥檚 research is focused on optimizing treatment for musculoskeletal injuries and diseases. With a primary focus on tendon, ligament and muscle, he seeks to understand healthy tissue function and structure, assess changes that occur in injury and disease, and develop therapeutics to improve outcomes.
Autoimmunity, Immunology and Inflammation
Molecular Microbiology and Immunology
The Rich DiPaolo group engages in studies of T cell responses to infection and disease. They have created technology to utilize information contained within the immune response, T cell receptor sequences, to develop assays to: diagnose infection, predict disease outcome, and evaluate vaccine efficacy. The approach includes, isolating and sequencing T cell receptors in blood, and using machine learning algorithms to develop a bioinformatic pipeline to use the sequence information to predict disease status. The group also engages in studies to understand how immune cells and cytokines contribute to autoimmunity, cancer, and other inflammatory diseases. This approach includes identifying immunoregulatory cells, including regulatory T cells (Tregs), and cytokines that can be manipulated using immunotherapies to develop new treatments for disease.Biochemistry and Molecular Biology
The Angel Baldan laboratory is interested in sterol homeostasis and in the molecular mechanisms involved in the conversion of macrophages into foam cells. This latter process is particularly relevant in several human pathologies, including atherosclerosis and different pulmonary lipidosis syndromes.Molecular Microbiology and Immunology
Rajeev Aurora studies mechanisms that lead to chronic inflammation in the context of osteoimmunology, osteoarthritis, and bone degeneration. His lab uses mouse models and human studies, employing computational and laboratory tools to understand the genetic, epigenetic, and environmental factors that lead from acute inflammation to chronic activation of the immune system. He holds multiple patents on treatments for bone degeneration diseases.Biochemistry and Molecular Biology
Pathological activation of the complement and clotting cascades leads to thrombosis and chronic inflammation, and is linked to the onset and progression of autoimmune disorders. Nicola Pozzi鈥檚 laboratory studies the unknown biology of complement and clotting factors, investigate their structure-function relationships, identify new ligands and define their mechanisms of recognition. Finally, they engineer novel constructs to correct the disease state. His current work focuses on the structures of proteins involved in Antiphospholipid Syndrome (APS), as well as the role of protein disulfide isomerases in thrombosis, cancer, and neurodegeneration. The recent development of a novel family of anticoagulant fusion proteins to ameliorate the outcome of patients suffering from thrombosis in acute clinical settings such as sepsis and stroke is an example of their work.Molecular Microbiology and Immunology
Daniel Hawiger researches the alleviation of autoimmunity by targeting antigens to dendritic cells and modifying effector and tolerogenic T cell functions. Hawiger studies mechanisms by which DCs govern T cell tolerance in the context of autoimmune disorders such as multiple sclerosis (MS) and other immune responses. His laboratory explores the roles of specialized subsets of DCs and their specific functions in tolerance as well as the relevant molecular mechanisms induced by such DCs in T cells. Their work has elucidated the functions of specific immunomodulatory pathways, cell signaling regulators and transcription factors that establish tolerogenic outcomes of the interactions between T cells and DCs.Molecular Microbiology and Immunology
Immunotherapy relies on tumor-specific T cells to target and eradicate cancer cells, and this potential has motivated immunologists and oncologists for many decades. Despite tremendous recent success, translating immunotherapy into a reliable treatment option for most cancer patients is still not a reality. One of the major challenges to successful immunotherapy is the induction of T cell tolerance within patients. Tolerance is multifaceted, involving both the death of tumor-reactive T cells and the induction of anergy, which renders any surviving T cells inert. Research in the Teague lab aims to identify and therapeutically target the molecular mechanisms that regulate T cell tolerance as a means to boost anti-tumor immunity, and ultimately to inform translational efforts to provide enhanced immunotherapy for patients with cancer.
Molecular Microbiology and Immunology
stephen.ferris@health.slu.edu;
The Ferris lab researches the basic mechanisms that drive immune responses, specifically focusing on ways to inhibit autoimmunity and augment cancer immune responses. They use multiple models of genetic manipulation to ask fundamental immunological questions during autoimmune and cancer immune processes.
The Ferris lab approaches involve the use of transgenic and knock out mouse models, CRISPR-targeted genetic manipulation, overexpression of desired genes, and flow cytometry. They use NOD mice and tumor cell lines to investigate the basic immune responses to self antigens in vivo and in vitro and use a combination of immune cell-based assays to interrogate function. They have generated dendritic cell-based vaccine strategies augmenting cancer immune responses or inhibiting autoimmune responses. Overall, their is on understanding basic immunological processes with the goals of optimizing cancer immune responses and inhibiting autoimmunity.
Abdominal Transplant Center, Nephrology, Internal Medicine
yasar.caliskan@health.slu.edu;
Yasar Caliskan's research is grounded novel integration and application of collaborative
precision medicine program in nephrology and transplantation practice using novel
genetic tools and biomarkers. Underlying themes of his research to date have included
efforts to advance understanding of:
1) the clinical implementation of genetic tools in Nephrology and Transplantation
practice,
2) biomarkers in kidney transplantation and glomerulonephritis
3) health outcomes in kidney transplant recipients and donors.
Caliskan serves as a principal investigator (PI) of 91女神 President鈥檚 Research Fund awarded project 鈥淢olecular Phenotyping of Graft Ischemia-Reperfusion injury and Normothermic Ex Vivo Kidney Perfusion with Single Cell RNA Sequencing鈥�. He is a co-PI for the project 鈥淎POL1 Genetic Testing: Exploring Knowledge and Attitudes to Improve Comprehensive Kidney Risk Assessment for Patients and Families鈥�. He is also PI on the National Institutes of Diabetes and Digestion and Kidney Disease (NIDDK) Cure Glomerulonephropathy Network (CureGN) Ancillary study 鈥淐linical Significance of Glomerular Immunodeposits in IgA Nephropathy (IgAN) and Focal Segmental Glomerulosclerosis (FSGS)鈥�.
Caliskan has over 130 publications, and serves as co-chair, board member, and expert in the international Clinical Genome Resource (ClinGen) consortium.
Molecular Microbiology and Immunology
Carrero鈥檚 interest is to understand how inflammation triggered by infection or autoimmunity impacts the development of cancer. Multiple cancers have been causally linked to chronic infectious diseases and/or autoimmune syndromes. By evaluating two models of stomach inflammation: Helicobacter pylori and autoimmune gastritis, the Carrero Laboratory seeks to identify mechanisms of gastric cancer induction that may lead to better diagnostics and therapeutics.
Cancer
Molecular Microbiology and Immunology
Edwin Antony utilizes biophysical and biochemical approaches to understand enzyme kinetics, structure and function during DNA repair and electron transfer. These foundational studies inform on methods to treat and prevent cancer. His lab is also advancing the use of non-canonical amino acids for studying enzyme assembly during DNA repair.Chemistry
Chris Arnatt utilizes organic and synthetic chemistry to generate targeted small molecules for research on cellular processes, disease states, and therapy. He has a special interest in developing chemical and fluorescent probes to study biologic systems, and focuses his research on nuclear proteins and DNA modifications in cancer and stem cell biology. Much of their current research is focused on deciphering the protein-ligand interactions of the G Protein-Coupled Estrogen Receptor (GPER, GPR30). Through collaborations with biologists, pharmacologists, and geneticists at 91女神 and the Albert Einstein School of Medicine, they have begun to reveal GPER plays a role in neurological development and gallstone formation.Molecular Microbiology and Immunology
Immunotherapy relies on tumor-specific T cells to target and eradicate cancer cells, and this potential has motivated immunologists and oncologists for many decades. Despite tremendous recent success, translating immunotherapy into a reliable treatment option for most cancer patients is still not a reality. One of the major challenges to successful immunotherapy is the induction of T cell tolerance within patients. Tolerance is multifaceted, involving both the death of tumor-reactive T cells and the induction of anergy, which renders any surviving T cells inert. Research in the Teague lab aims to identify and therapeutically target the molecular mechanisms that regulate T cell tolerance as a means to boost anti-tumor immunity, and ultimately to inform translational efforts to provide enhanced immunotherapy for patients with cancer.Biochemistry and Molecular Biology
susana.gonzalohervas@health.slu.edu;
Susana Gonzalo's long-term research interest is to understand the molecular mechanisms that contribute to the genomic instability that drives aging and cancer, with the goal of targeting these mechanisms therapeutically. Nuclear lamins orchestrate genome organization, forming a scaffold for tethering chromatin and protein complexes regulating many nuclear functions. Lamins dysfunction impacts nuclear architecture, chromatin structure, as well as DNA transcription, replication and repair. These data, and the association of lamins dysfunction with dozens of degenerative disorders, premature aging, and cancer, provide evidence for these proteins operating as 鈥渃aretakers of the genome." Gonzalo's research focuses on identifying mechanisms whereby lamins regulate genome stability and function, as these mechanisms are key to identify therapies that ameliorate the progression of laminopathies in patients.
Biochemistry and Molecular Biology
The Korolev lab studies the mechanism of protein function using X-ray crystallography combined with biophysical and biochemical methods. Systems of interest include 1) recombination mediator proteins (RMPs) important for genome maintenance, DNA repair and implicated in cancer (BRCA1/2, PALB2) and pathogen drug resistance; 2) DNA helicases involved in DNA replication and repair; 3) calcium-independent phospholipase (iPLA2B) critical for inflammation, calcium homeostasis and implicated in a wide spectrum of diseases from ischemia to neurodegeneration.Molecular Microbiology and Immunology
Elise Alspach鈥檚 research program seeks to identify interactions between immune cells and fibroblasts present within the tumor microenvironment that can be targeted to enhance the efficacy of immunotherapies. While fibroblast cells are known to promote tumor growth and progression, little is known about fibroblast populations direct impact on tumor infiltrating T cell responses. Alspach is working to define fibroblasts as an immunosuppressive population within the tumor microenvironment, and to identify tractable therapeutic targets that disrupt these interactions.Biology
Sofia Origanti studies regulation of protein synthesis with a focus on eukaryotic initiation factors (eIFs). Many eIFs are overexpressed in cancers and serve to enhance cancer growth. eIF6 is one such factor that is overexpressed in many types of cancers and serves as a potential therapeutic target for inhibiting cancer growth and progression. eIF6 is also deregulated in the rare disorder Shwachman-Diamond syndrome (SDS) and targeting eIF6 has been proposed as a potential therapeutic mechanism for treating SDS.Pathology
Ratna Ray's laboratory in focused on studying chemopreventive and therapeutic effects on several solid tumors in preclinical models using a natural product, Bitter Melon (Momordica charantia). They have excellent results from their preclinical studies. Currently, they are identifying the active component(s) of bitter melon in collaboration with Bahaa Elgendy. Their initial experiments have identified a number of components with potential beneficial effects requiring further study.Biochemistry and Molecular Biology
The Vindigni laboratory focuses on the mechanisms of DNA replication and repair, and on the possible strategies to target these mechanisms for cancer treatment. Aberrant DNA replication is one of the leading causes of mutations and chromosome rearrangements associated with several cancer related pathologies. At the same time, agents that stall or damage DNA replication forks are widely used for chemotherapy, in the attempt to selectively target highly proliferating cancer cells. Their work provides a new rationale to design novel molecularly-guided treatments targeting the pathways of replication stress response to cancer chemotherapeutics.Pharmacology and Physiology
Jinsong Zhang studies the interplay of transcription factors, corepressors and coactivators in the regulation of chromatin and transcription, which ultimately leads to changes of gene expression in various cell differentiation, development and disease pathways. Zhang focuses on leukemia fusion proteins, nuclear receptor corepressors, and histone deacetylases (HDACS). Zhang has identified multiple therapeutic targets, including in the AML1-ETO axis and in novel HDAC1 complexesPediatric Hematology/Oncology, Pediatrics
William Ferguson鈥檚 researches and treats pediatric oncology patients, with an interest in newly diagnosed osteosarcoma, Ewing sarcoma, and other soft tissue sarcomas. Ferguson engages in clinical trials evaluating new antineoplastic agents in the treatment of solid tumors, currently active in neuroblastoma. Ferguson also studies new drug therapies to prevent and treat complications of sickle cell disease. He is the institutional principal investigator for the Children's Oncology Group and the Neuroblastoma and Medulloblastoma Translational Research Consortium.Physics
The mechanical properties of cells are tightly correlated to many biological events, such as embryonic development, cell differentiation, aging, disease progression, and cancer metastasis. However, the interplay between cells鈥� deformability as well as the internal forces, and their importance in cell signaling and fate have been insufficiently investigated. Amina Mohammadalipour鈥檚 interdisciplinary research is centered upon the biophysical aspects of carcinogenesis from initiation and growth to progression and metastasis. New insights into the biophysical-driven cellular and subcellular functions, which critically regulate tumor invasion, will contribute to the development of drug discovery and therapeutic innovations.Pathology; Molecular Microbiology and Immunology
Research Scientist, St Louis VA Healthcare System
jacki.kornbluth@health.slu.edu
Jacki Kornbluth studies the role of natural killer (NK) cells in the immune response to tumors and pathogenic infection. Her laboratory has developed the only normal NK cell line (NK3.3) to date and continues to characterize key molecules mediating NK cell activity. They recently found that when activated, NK3.3 cells release extracellular vesicles (EVs) that are extremely potent in killing a broad array of tumor cells but do not kill normal cells. In addition, EVs can be produced in large quantities, and are stable when frozen, stored and thawed without loss of function. Therefore, NK3.3-derived EVs have the potential to be an 鈥渙ff-the-shelf鈥� product for the treatment of many different types of cancer. Mouse models of human myeloma and breast cancer are being used to test the ability of NK-derived EVs to mediate anti-tumor activity in vivo as proof of concept that EVs have therapeutic potential. Preliminary results indicate that NK3.3-derived EVs kill these tumor cells in vitro and in vivo. NK cells also kill cells infected with herpes, influenza and hepatitis viruses. The ability of NK3.3-derived EVs to treat viral infections remains to be determined but may have tremendous therapeutic potential.
Chair, Department of Chemistry
The Demchenko laboratory, Glycoworld, has trained more than 150 researchers and has developed many innovative tools for the synthesis and application of carbohydrates (glycans or glycoconjugates) in five major areas:
- New synthetic reagents and building blocks;
- Reactions for stereocontrolled glycosylation;
- Expeditious strategies and automated technologies for oligosaccharide synthesis;
- Biomedical studies on the development of glycopharmaceuticals; and
- Integration of glycans and nanomaterials in carbohydrate nanotechnology.
Some of these methods have been applied to the synthesis of tumor-associated glycosphingolipids to study their roles in the metastasis of cancers and in pathogenesis of neurodegenerative diseases; glycoconjugates of important bacterial pathogens Streptococcus pneumoniae and Staphylococcus aureus for vaccine development; glycopeptides as LPS antagonists for treating septicemia and for the development of Alzheimer's disease therapeutics; human milk oligosaccharides to study their functions, and carbohydrate-based imaging reagents, enzyme inhibitors, and personalized vaccine adjuvants.
Molecular Microbiology and Immunology
stephen.ferris@health.slu.edu;
The Ferris lab researches the basic mechanisms that drive immune responses, specifically focusing on ways to inhibit autoimmunity and augment cancer immune responses. They use multiple models of genetic manipulation to ask fundamental immunological questions during autoimmune and cancer immune processes.
The Ferris lab approaches involve the use of transgenic and knock-out mouse models, CRISPR-targeted genetic manipulation, overexpression of desired genes, and flow cytometry. They use NOD mice and tumor cell lines to investigate the basic immune responses to self antigens in vivo and in vitro and use a combination of immune cell-based assays to interrogate function. They have generated dendritic cell-based vaccine strategies augmenting cancer immune responses or inhibiting autoimmune responses. Overall, there is an understanding basic immunological processes with the goals of optimizing cancer immune responses and inhibiting autoimmunity.
Molecular Microbiology and Immunology
melissa.berrien@health.slu.edu;
The Berrien-Elliott laboratory uses preclinical and translational approaches to understand how natural killer (NK) cells are impacted by cancer immunotherapies and how the tumor microenvironment contributes to immune evasion. The goal of this research is to develop these mechanistic insights into novel treatments for patients. Recent work has identified enhanced NK cell functionality after brief cytokine activation. These cytokine-induced memory-like (ML) NK cells are being tested in the clinic and are safe. Berrien-Elliott is developing approaches combining these ML NK cells with various tumor-targeting strategies, such as chimeric-antigen receptors and tumor-targeting antibodies in order to treat a wider variety of tumors, including solid tumors. The lab focuses on understanding how ML NK cell therapies can impact the endogenous immune system and the cross-talk between NK cells and the tumor microenvironment.
Berrien-Elliott is a co-founder of WUGEN INC, an allogeneic cellular therapy start-up with multiple cell products currently in clinic testing.
Molecular Microbiology and Immunology
javier.carrero@health.slu.edu;
Carrero鈥檚 interest is to understand how inflammation triggered by infection or autoimmunity impacts the development of cancer. Multiple cancers have been causally linked to chronic infectious diseases and/or autoimmune syndromes. By evaluating two models of stomach inflammation: Helicobacter pylori and autoimmune gastritis, the Carrero Laboratory seeks to identify mechanisms of gastric cancer induction that may lead to better diagnostics and therapeutics.
Medicinal Chemistry and Pharmacology
Department of Chemistry
The core theme of research in the Arnatt Lab revolves around utilizing organic chemistry to decipher cellular processes and disease states. Specifically, they are developing novel small molecule chemical probes and fluorescent probes to study biological systems. Much of their current research is focused on deciphering the protein-ligand interactions of the G Protein-Coupled Estrogen Receptor (GPER, GPR30). Very little is known about how this non-traditional estrogen receptor interacts with estrogen and modulates hormonal signaling inside of cells. The goal of their research is to design ligands that bind to GPER, identify selective agonists and antagonists, characterize their interactions with the receptor, analyze those interactions to develop ligands, which can modulate receptor function in cells, and determine their therapeutic potential. Their laboratory performs both the medicinal chemistry and pharmacology research for this project and has developed the first-ever high-throughput assays for this receptor. Through collaborations with biologists, pharmacologists, and geneticists at 91女神 and the Albert Einstein School of Medicine, they have begun to reveal GPER plays a role in neurological development and gallstone formation.
Pharmacology and Physiology, Center for Clinical Pharmacology, University of Health Sciences and Pharmacy in St. Louis
bahaa.elgendy@uhsp.edu; belgendy@wustl.edu;
The main focus of Elgendy鈥檚 research group is medicinal chemistry with a broad goal of drug design and optimization. Most of the work in his lab concentrates on developing small molecules modulators for different targets. For example, he designs and synthesize modulators of nuclear hormone receptors for the therapeutic treatment of cancer and fatty liver diseases. Also, he develops small molecules that can act as anti-viral agents against HCV, ZIKV, and other microbes. He has a wide international collaboration with scientists from the United Kingdom, United Arab Emirates and Egypt, as well as locally at 91女神, Washington University, and other regional universities. Elgendy incorporates computational methods such as quantitative-structure-activity relationships, pharmacophore modeling, and virtual screening in his drug discovery pipeline to accelerate the process of drug discovery and optimization.
Chemistry
The primary research focus in their lab is structure-function relationships of heme proteins that play important roles in human physiology. More specifically, they focus on understanding the structural features that control heme enzyme activities, including active site environments, substrate-assisted catalysis, drug-drug interactions, suicide inhibition and protein environmental conditions, such as the nature of the interactions with redox partners and cofactors. The primary tool in the lab is resonance Raman (rR) spectroscopy, complemented by the application of electronic absorption, EPR and NMR spectroscopies. An innovative combination of cryoradiolysis method to generate and trap unstable enzymatic intermediates with rR spectroscopy allows effective interrogation of previously inaccessible catalytic intermediates. Altogether, these studies can provide valuable guidelines towards design of new selective and efficient drugs and protein inhibitors.
The current research subjects are human heme oxygenase, a promising therapeutic target for atherosclerotic, inflammation, allergy and anticancer treatments as well as cytochromes P450 involved in physiology and virulence of human pathogen Mycobacterium tuberculosis.
Chemistry, Pharmacology and Physiology
The research in Meyer's lab is focused on the application of medicinal chemistry toward the discovery of potential drug candidates to treat people with rare and neglected diseases. They collaborate with experts in infectious disease biology, including malaria, tuberculosis, infectious diarrhea (cryptosporidiosis), cryptococcal meningitis, hepatitis B virus, and herpes simplex virus. They also have ongoing collaborations with experts in oncology, FSHD muscular dystrophy, and infant short-gut syndrome.
They use synthetic organic chemistry techniques to prepare new compounds, which are analyzed by their collaborators to assess their biological properties. Using medicinal chemistry and structure-based drug design principles, they optimize the potency, pharmacokinetics, and safety profiles of compounds with the goals of identification of tool compounds and, ultimately, candidate drug molecules for clinical trials.
Pharmacology and Physiology
john.walker@health.slu.edu ; Website;
Research in the Walker lab focuses mainly on synthetic and medicinal chemistry to develop tool compounds or novel therapeutic agents against a variety of biological targets and therapeutic indications. The lab is actively involved in multiple research collaborations partnering with investigators both at 91女神 and other Universities. They use modern synthesis techniques and also a number of in silico approaches to design and synthesize new target molecules.
A major area of research focus and collaboration for their group is developing strategies and molecules to target antibacterial resistance as part of their long-standing collaboration with the Zgurskaya and Rybenkov labs at the University of Oklahoma. They are working to develop molecules that can penetrate the outer membrane of Gram-negative pathogens and inhibit efflux pumps, which contribute both to the intrinsic and acquired resistance of many pathogens to antibiotics. They recently demonstrated that novel ligands they prepared can potentiate the activity of the antibiotics novobiocin and erythromycin in E. coli.
Chemistry
Research in the Znosko laboratory focuses on the thermodynamics and structural features of RNA motifs. While sequences of many important RNAs have been determined, little is known about structure-function relationships of RNA. One reason for this lack of information is that there is little definitive secondary and tertiary structural information about RNA. X-ray crystallography and NMR methods are providing an increasing number of RNA structures, but it is unlikely that these methods will keep pace with the rate at which interesting sequences are being discovered. Thus, there is a need for reliable, rapid methods to predict secondary and tertiary structures of RNA. Being able to predict secondary and tertiary structures of RNA provides a foundation for determining structure-function relationships for RNA and for targeting RNA with therapeutics. A broad, long-term objective of the laboratory is to improve RNA secondary and tertiary structure prediction from sequence.
Biochemistry and Molecular Biology
sergey.korolev@health.slu.edu;
The Korolev lab studies the mechanism of protein function using X-ray crystallography combined with biophysical and biochemical methods. Systems of interest include 1) recombination mediator proteins (RMPs) important for genome maintenance, DNA repair and implicated in cancer (BRCA1/2, PALB2) and pathogen drug resistance; 2) DNA helicases involved in DNA replication and repair; 3) calcium-independent phospholipase (iPLA2B) critical for inflammation, calcium homeostasis and implicated in a wide spectrum of diseases from ischemia to neurodegeneration.
Pharmacology and Physiology
The de Vera lab focuses on drug discovery efforts targeting orphan nuclear receptors (NRs). They have developed and utilized an array of biophysical methods for high-throughput screening of compounds binding the Germ Cell Nuclear Factor (GCNF), which holds great promise to the future of stem cell therapy and the development of anti-sterility drugs for men. Their goal is to identify the endogenous metabolite of orphan nuclear receptors using in-silico molecular docking of compound libraries to orphan NR targets, in tandem with a liquid chromatography-mass spectrometry (LC-MS) metabolomics platform. The deorphanization of NRs could provide crucial clues to the structure of synthetic compounds that would fit the binding pocket. They will use X-ray crystallography to structurally confirm specific binding of drugs and endogenous metabolites to NRs, and NMR spectroscopy techniques to characterize the interaction dynamics. The invaluable structural and dynamics information will aid structure optimization of synthetic compounds for better drug potency and efficacy. They will be working closely with other members of the 91女神-IDBI, including John Tavis, Marvin Meyers, Feng Cao, Maureen Donlin, Lynda Morrison and Getahun Abate on drug discovery efforts.Pharmaceutical and Administrative Sciences, University of Health Sciences and Pharmacy in St. Louis
Lamees Hegazy performs research on the rational design and optimization of therapeutic compounds using molecular modeling and computational biochemistry methods. Hegazy uses structure and ligand-based approaches for computational simulations of molecular dynamics and free energy based optimization studies. She collaborates with many other 91女神-IDBI members, and widely throughout the Saint Louis research community.Department of Health Sciences, Nursing and Public Health; Chemistry; 91女神-Madrid
Tania de la Fuente performs studies on the serotonin 5-HT6 receptor and designs ligands for CNS conditions. Based in Madrid, Spain, de la Fuente collaborates with researchers throughout Europe to provide medicinal chemistry and subject specific expertise.Chair, Department of Chemistry
The Demchenko laboratory, Glycoworld, has trained more than 150 researchers and has developed many innovative tools for the synthesis and application of carbohydrates (glycans or glycoconjugates) in five major areas:
- New synthetic reagents and building blocks;
- Reactions for stereocontrolled glycosylation;
- Expeditious strategies and automated technologies for oligosaccharide synthesis;
- Biomedical studies on the development of glycopharmaceuticals; and
- Integration of glycans and nanomaterials in carbohydrate nanotechnology.
Some of these methods have been applied to the synthesis of tumor-associated glycosphingolipids to study their roles in metastasis of cancers and in pathogenesis of neurodegenerative diseases; glycoconjugates of important bacterial pathogens Streptococcus pneumoniae and Staphylococcus aureus for vaccine development; glycopeptides as LPS antagonists for treating septicemia and for the development of Alzheimer's disease therapeutics; human milk oligosaccharides to study their functions, and carbohydrate-based imaging reagents, enzyme inhibitors, and personalized vaccine adjuvants.
Chemistry
welivitiya.karunarathne@slu.edu; Website
The interdisciplinary research projects in Ajith Karunarathne's lab bridge Biological-bioanalytical Chemistry, Chemical Biology, and Molecular Pharmacology. The group takes a reductionist approach when dissecting biological processes at the subcellular level and multiplexing nature-endowed properties of signaling molecules to engineer molecular tools and signaling pathways to uncover the chemistry behind diseases while fueling discovery and therapy. Projects in Karunarathne's lab include (i) chemical biology-oriented, photo-pharmacological tools engineering to control signaling and behaviors of intact and genetical unmodified cells, (ii) bio-analytical and molecular signaling-based cellular assay development and screening of less addictive ligands for opioid receptors, (iii) development of optogenetic and small molecule modulators of GPCRs and G proteins, and (iii) decoding chemistry of photopigment proteins and their re-engineering for in vivo applications.
Chemistry
malkanthi.karunananda@slu.edu;
Research in the Karunananda Lab strategically leverages a combination of synthetic inorganic, organometallic, and computational chemistry techniques to solve pressing challenges in catalysis. The overall research theme is built on employing multiple metals and/or multiple ligands to synergistically bring about novel reactivity and selectivity. A special focus is placed on interrogating reaction mechanisms through experimental and computational techniques to predict and design novel catalysts.
Current projects in the lab include photosensitizer development using earth-abundant metals with target applications in organic synthesis & photodynamic therapies, and organometallic catalyst development for polymer upcycling. The experimental work in the lab focuses on multi-metallic complex synthesis, characterization and catalytic reaction development. The computational work in the lab focuses on photoreactivity and catalyst optimization with DFT calculations, statistical analysis, and machine learning approaches.
Clinical Studies
Internal Medicine, Gastroenterology; 91女神 Liver Center
Brent Tetri is an international expert on non-alcoholic fatty liver disease (NASH/NFLD), studying mechanisms of disease formation, progression, and therapeutics. He has developed widely used animal models of NASH, as well as models, methods and assays to study pancreatitis. Tetri is regularly called upon to provide expert consultation to industry on pre-clinical studies, clinical study design, and clinical study endpoint selection in the liver and pancreatic diseases.Pediatrics; Biochemistry and Molecular Biology
Jeffrey Teckman is chair of the Department of Pediatrics, and a practicing pediatric gastroenterologist. Teckman is a world authority in the metabolic disease alpha-1-antitrypsin deficiency, is published and recognized in other liver diseases, and is an experienced consultant to industry and has been involved in FDA applications. His 25 years of academic research have involved molecular biology, cell biology, protein trafficking, and rare diseases focused on liver injury, genetic-metabolic disease, and liver therapeutics. Teckman also has 20 years experience in continuously funded clinical research, including industry trials phases 1, 2 and 3, multi-center natural history studies and international database trials.Clinical Pathology, Bloodbanking and Transfusion Medicine
Alex Babic is a trained clinical pathologist within the 91女神 and SSM Health hospital system. The research interests of Aleksandar Babic, M.D., are focused on the evaluation of outcomes of umbilical cord blood (UCB) transplantation. Babic was recruited as medical director at St. Louis Cord Blood Bank and subsequently became medical director of the combined 91女神 Cellular Therapy Laboratory. He is medical director of the pediatric hematology and oncology apheresis program.Gastroenterology and Hepatology, Internal Medicine
Kamran Qureshi鈥檚 research interests include liver cirrhosis, portal hypertension, liver cancer and NASH. As a clinician, Qureshi treats patients for a range of liver diseases, including autoimmune liver diseases, cancer, cirrhosis, and infectious hepatitis. He performs endoscopic screening procedures as well as manages patient liver transplants.Pediatric Hematology/Oncology, Pediatrics
William Ferguson鈥檚 researches and treats pediatric oncology patients, with an interest in newly diagnosed osteosarcoma, Ewing sarcoma, and other soft tissue sarcomas. Ferguson engages in clinical trials evaluating new antineoplastic agents in the treatment of solid tumors, currently active in neuroblastoma. Ferguson also studies new drug therapies to prevent and treat complications of sickle cell disease. He is the institutional principal investigator for the Children's Oncology Group and the Neuroblastoma and Medulloblastoma Translational Research Consortium.Director of Clinical Microbiology; Medical Director of Molecular Microbiology, 91女神 Hospital
Robin Chamberland directs the clinical microbiology labs at SSM 91女神 Hospital. She assists 91女神-IDBI investigators who may need access to clinical samples and provides clinical perspective to 91女神-IDBI investigators. Chamberland studies antimicrobial resistance in S. aureus, a relatively common commensal bacterium that causes opportunistic infections with growing drug resistance. She also studies bacterial toxins and their interaction with the host innate immune system. She focuses on the setting of S. aureus necrotizing pneumonia.Infectious Diseases
The development of new drugs against mycobacterial diseases is one of Abate鈥檚 key research interests. His lab works closely with the Hoft lab, and has the following capacities: screening new drugs against bacillus Calmitte Guerin (the attenuated TB vaccine) using a rapid growth inhibition assay, testing drugs on reference strains of Mycobacterium tuberculosis and M. avium, studying anti-mycobacterial activities against intracellular mycobacteria using human macrophages from healthy donors, testing interactions of new drugs with first-line anti-TB drugs against extracellular and intracellular mycobacteria, studying the effects of new drugs on mycobacterium-specific immunity and testing the cytotoxicity of new drugs on THP-1 (human) and J774.A1 (murine) macrophage cell lines. His lab also has a protocol to test the anti-TB activities of new drugs in murine TB model.91女神 Infectious Diseases Division; Clinical Director, Center for Vaccine Development
Sharon Frey is a practicing infectious diseases physician. Her research expertise is in testing of vaccine candidates in Phase I 鈥� III clinical trials. She provides guidance to 91女神-IDBI members regarding in the medical needs and issues associated with microbial infections of human patients, and also helps guide design of clinical trials of novel drug candidates.
St. Louis Veteran's Administration Hospital and 91女神 Infectious Diseases Division
Sarah George is a clinician-scientist who both cares for patients and conducts biomedical research. Her laboratory effort focuses on innate and adaptive immune responses to flavivirus infections. Her lab is currently focused on identifying human adaptive immune responses which control dengue replication in target cells. George has been the Principal Investigator on numerous vaccine and therapeutic clinical trials, most recently for SARS-CoV-2. She has extensive expertise in developing clinical trials protocols and monitoring human subject safety in clinical trials. Her laboratory can measure ex vivo efficacy of agents designed to boost human memory immune responses which control dengue replication. George鈥檚 lab also has extensive experience with HIV and human pegivirus (HPgV), and can test compounds which may inhibit HIV replication or enhance HPgV鈥檚 inhibitory effect on HIV replication.
Infectious Diseases; Director, Center for Vaccine Development
daniel.hoft@health.slu.edu; Center for Vaccine Development Website
Daniel Hoft is the chief of the 91女神 Division of Infectious Diseases, Allergy and Immunology and director of the 91女神 Center for Vaccine Development. Hoft studies the immune response to multiple intracellular pathogens including Mycobacterium tuberculosis and Trypanosoma cruzi, and works collaboratively to develop and support studies for new drugs against these pathogens.. He has also contributed extensively to the development of multiple vaccines including generating 91女神-held IP for a universal flu vaccine, and the development of a multi-omics core for studying vaccine responses. Hoft leads the extended stay research unit of the Vaccine Center, allowing for vaccine-challenge studies against flu and many other pathogens.
Medical Imaging and Radiation Therapeutics
Nabil Khater is the chief physicist in the Department of Radiation Oncology. Khaters research focuses on the development of software, methods, and techniques to enable and improve the usage of radiotherapy imaging and treatment. Khater has led and contributed to development of many commercial software, method, and protocol packages to improve patient monitoring and surgical outcomes. He has recently been awarded support from the Research Institute to design, build, and test an adaptable headrest for image-guided radiotherapy (IGRT) of head and neck cancers.Obstetrics and Gynecology
Niraj Chavan, M.D., is the medical director of the Women and Infant Substance Help (WISH) Center at SSM Health St. Mary's Hospital, and assistant director of the Maternal Fetal Medicine Fellowship Program at 91女神 School of Medicine. He is a specialist in high-risk pregnancies, particularly involving substance use during pregnancy. Other areas of expertise include maternal medical complications, such as cardiovascular, neurological, renal and autoimmune conditions, hypertensive disorders of pregnancy, preterm birth, placenta accreta spectrum, and multiple gestations.
Chavan's research interests include disparities in maternal morbidity and mortality, health equity, preterm birth prevention, cardiac disease in pregnancy, quality improvement and development of best practices in perinatal addiction.
Abdominal Transplant Center, Nephrology, Internal Medicine
yasar.caliskan@health.slu.edu;
Yasar Caliskan's research is grounded novel integration and application of collaborative
precision medicine program in nephrology and transplantation practice using novel
genetic tools and biomarkers. Underlying themes of his research to date have included
efforts to advance understanding of:
1) the clinical implementation of genetic tools in nephrology and transplantation
practice,
2) biomarkers in kidney transplantation and glomerulonephritis
3) health outcomes in kidney transplant recipients and donors.
Caliskan serves as a principal investigator (PI) of 91女神 President鈥檚 Research Fund awarded project 鈥淢olecular Phenotyping of Graft Ischemia-Reperfusion injury and Normothermic Ex Vivo Kidney Perfusion with Single Cell RNA Sequencing鈥�. He is a co-PI for the project 鈥淎POL1 Genetic Testing: Exploring Knowledge and Attitudes to Improve Comprehensive Kidney Risk Assessment for Patients and Families鈥�. He is also PI on the National Institutes of Diabetes and Digestion and Kidney Disease (NIDDK) Cure Glomerulonephropathy Network (CureGN) Ancillary study 鈥淐linical Significance of Glomerular Immunodeposits in IgA Nephropathy (IgAN) and Focal Segmental Glomerulosclerosis (FSGS)鈥�.
Caliskan has over 130 publications, and serves as co-chair, board member, and expert in the international Clinical Genome Resource (ClinGen) consortium.
Pediatric Gastroenterology, Pediatrics
Ajay Jain鈥檚 research interests include pediatric liver and gut diseases and nutrition. The Jain lab evaluates strategies targeting liver and gut injury noted in short bowel syndrome (SBS), which results from bowel resection or lack of functional gut. SBS patients require intravenous nutrition through a process called Total Parenteral Nutrition (TPN). Despite being a life saver, complications in SBS include life threatening and potentially fatal, intestinal failure associated liver disease (IFALD) as well as gut injury with gut mucosal atrophy and increase gut permeability. The lab studies many aspects of SBS and nutrition, including the role of gut microbiota in TPN associated injury, and markers of nutritional status and injury. Jain lab is currently evaluating novel molecules in mitigating injury associated with SBS, under a $1.9 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
Jain is the director of the M.D./Ph.D. program at 91女神 School of Medicine, and medical director of the pediatric liver transplant program at SSM Health Cardinal Glennon Children鈥檚 Hospital.
Internal Medicine - Infectious Diseases
Brett Jagger, Ph.D., conducts clinical trials at 91女神's Center for Vaccine Development (CVD), including studies initiated through the NIAID Vaccine and Treatment Evaluation Unit (VTEU) network. He is trained in molecular virology as well as pre-clinical vaccine development, and is interested in developing antiviral as well as immunomodulatory therapeutics for arboviral and respiratory viral pathogens, especially encephalitic arboviruses and influenza. His goal is to advance therapeutics for these viral diseases across the continuum of drug development, from in silico screens, through validation in laboratory and animal model systems, and ultimately, human clinical trials. He is also interested in the development of Controlled Human Infection Models (CHIMs) to advance the prevention and treatment of rare and emerging diseases, hosted at 91女神's Extended Stay Research Unit.
Pediatrics
robert.fleming@health.slu.edu;
Robert Fleming, M.D., is board-certified in pediatrics and neonatal-perineonatal medicine. His laboratory research studies the molecular mechanisms underlying absorption of dietary iron, and modulation of iron hemeostasis, iron metabolism, and erythropoiesis in settings of iron restriction, including anemia. Recent work has focused on studying improvements to disease markers with dietary iron restriction in murine models of sickle cell anemia, and the effects of iron transferrin on iron metabolism and erythropoiseis in settings of iron deficiency. Fleming is very interested in translational studies using diagnostic markers and treatments in clinical settings of iron deficiency, nutritional anemia and genetic disorders.
Pediatrics
Nermi Parrow studies iron metabolism, transport, and homeostasis in the context of health and disease. Parrow's research includes studies on anemia, iron deficiency (nutritional, genomic), and thalassemias.
Screening, Diagnostic, and Supporting Technologies
Biochemistry and Molecular Biology
Yie-Hwa Chang has been interested in developing anti-cancer drugs and antibiotics for the past 15 years. His lab has discovered and characterized two types of methionine aminopeptidases (MetAPs). The type-2 MetAP plays a key role in angiogenesis, and has been identified as a potential target for developing anti-cancer and anti-obesity drugs. Their discovery was licensed to 11 major pharmaceutical companies for their drug discovery projects. His lab has worked with David Griggs and Eric Jacobsen. Together, they have identified promising leading compounds as potential anti-TB drugs via inhibition of the MetAPs. In addition, he has been collaborating with Tomasz Heyduk, and have developed a series of novel homogeneous assays that have been used by many pharmaceutical companies for high-throughput drug screening projects. For example, his lab developed the first homogeneous assay for cAMP, S-adenosylmethionine (SAMe) and L-tryptophan. The cAMP assay has been used for developing drugs targeting GPCRs. The SAMe assay has been used for developing drugs for targeting methyltransferases. Finally, the L-tryptophan assay has been used for developing drugs targeting Indoleamine 2,3-dioxygenase (IDO1/IDO2). IDO1 is an important immunotherapy target for cancer treatment.Chemistry
Paul Bracher鈥檚 research focuses on organic and inorganic chemistry of prospective importance to the origin of life. Our planets greatest unsolved mystery is the question of how first networks of reactions developed on Earth and became living systems. Research in the lab addresses significant questions on the origins of life, as well as yielding technologies of practical importance, these areas include: studies of the reactions of thioesters, thiocarbonates, thiocarbamates and related compounds in reactions catalyzed by metal complexes and competitively with hydrolysis; using earth-abundant minerals to catalyze photochemical reduction of CO2, generating chemical fuels from solar energy; and studying pre-biotic solvent systems for mediating organic reactions.Chemistry
Ryan McCulla鈥檚 research efforts broadly focus on the investigation and application development of photochemical reactions. His group is a recognized leader in the investigation of photodeoxygenation and its application in biological systems. Photodeoxygenation reactions are the only practical means of generating atomic oxygen [O(3P)] in solution, which distinguishes photodeoxygenation from photosensitization. Photosensitization generates singlet oxygen (1O2) and superoxide (O2鈥�) and is the mechanism behind the photodynamic therapy (PDT) for cancer, chromophore-assisted ligand inactivation (CALI), and photo-crosslinking. Since O(3P) reactivity is distinct from other reactive oxygen species (ROS), such as 1O2 and O2鈥�, photodeoxygenation is expected to provide complementary or alternative approaches to problems or diseases where photosensitization is unsuitable. Other research areas include developing conjugated polymer photoredox catalysts and the development of cell dyes.Biology
Wenyan Xiao studies the mechanism underlying epigenetic regulation of gene expression using the model plant Arabidopsis thaliana. DNA methylation is a heritable epigenetic phenomenon that plays an important role in genome integrity, X chromosome inactivation, silencing of transposons, gene expression and imprinting. Xiao鈥檚 current research is focused on elucidating the molecular mechanism of active DNA demethylation and dynamic changes of DNA methylation during growth and development.Molecular Microbiology and Immunology
The Rich DiPaolo group engages in studies of T cell responses to infection and disease. They have created technology to utilize information contained within the immune response, T cell receptor sequences, to develop assays to: diagnose infection, predict disease outcome, and evaluate vaccine efficacy. The approach includes, isolating and sequencing T cell receptors in blood, and using machine learning algorithms to develop a bioinformatic pipeline to use the sequence information to predict disease status. The group also engages in studies to understand how immune cells and cytokines contribute to autoimmunity, cancer, and other inflammatory diseases. This approach includes identifying immunoregulatory cells, including regulatory T cells (Tregs), and cytokines that can be manipulated using immunotherapies to develop new treatments for disease.Institute for Drug and Biotherapeutic Innovation
Abdul Mottaleb is an expert in therapeutic drug discovery with absorption, distribution, metabolism, execration (ADME)/ pharmacokinetics (PK) studies. He performs method development, validation, analysis and characterization by LC-MS for studies to support drug development in small molecules from in vitro and in/ex vivo samples. Mottaleb provides this support to IDBI, 91女神, and external researchers as a staff scientist for the IDBI ADME/PK Laboratory.Biochemistry and Molecular Biology
David Ford has pioneered the field of lipidomics to study mechanisms responsible for cardiovascular diseases. He combines expertise in physiological models of diseases with mass spectrometry and bio-organic techniques to interrogate alterations in lipid metabolism and signaling pathways involved with cardiovascular disease. Ford also applies these lipidomics techniques to collaborator studies including infectious diseases and vaccines. Ford is the Director of the Center for Cardiovascular Research.Chemistry
Research in the Martin group is focused on the development and use of microfluidic devices to study cell-to-cell communication. This includes the use of 3D printing as well as traditional microfabrication procedures to design devices that integrate 3-dimensional cell culture with analytical detection schemes. These devices are being used to create realistic in vitro models of in vivo systems. A major project is the development of microfluidic devices to devices containing cells cultured on ECM scaffolds coupled with online analytical assays to quantitatively study cell-cell interactions. They are utilizing these devices to study endothelial-macrophage interactions during inflammatory and healing atherosclerotic phenotypes. Other projects include the development of a microchip-based blood-brain barrier (BBB) mimic to study the effect of nitric oxide (NO) on the integrity of the BBB; microchip-based analysis/reactor system to study the effect of NO on the onset of Parkinson's disease; and new microchip and electrochemical materials to enable the detection of NO release from endothelial cells.Pathology, Research Microscopy and Histology Core
Grant.kolar@health.slu.edu; Microscopy and Histology Core Website
Grant Kolar is the director of the Research Microscopy and Histology Core within Saint Louis University, providing a wide range of equipment, histology services, and microscopy services to researchers at the University, other institutions, and businesses. Kolars research focuses on the cellular biology of deorphanized receptors and cognate peptides in the retinal pigmented epithelium of the eye.Clinical Health Sciences
Uthayashankar Ezekiel鈥檚 research interest are in diagnostic assay development, gene targeting, cellular differentiation, and the use of phytochemicals for cancer inhibition and treatment.Biology
Brian Downes investigates the ubiquitin pathway, and how proteins are selected and regulated for modification and degradation. Downes is particularly interested in identifying new mechanisms of specificity in ubiquitination. His lab focuses on the role of membrane-anchored Ubiquitin-fold (MUB) proteins, which localize specific components of the ubiquitin system to the plasma membrane. Downes is discovering the MUB interactome, defying structural characteristics of these protein complexes, and the role MUBs play in altering interacting protein functions.Aerospace and Mechanical Engineering
Mark McQuilling鈥檚 research interests include experimental fluid mechanics, low Reynolds number flows, laminar-to-turbulent transition, airfoil design (low-pressure turbine and low Reynolds number wings), unsteady aerodynamics (turbomachinery and airdrop systems), bio-fluid flows, and flow control.Physics
Martin Nikolo performs research on superconductivity and methods and technologies for magnetic measurements. He is an authority on ac susceptibility and ac susceptometer design. AC susceptibility is the method of detecting magnetization dynamics after application of an electric field. These measurements are critical to the detection and analysis of experiments using superconductor materials, and to advance the field of superconductivity, energy transfer and energy storage.Pharmacology and Physiology
The de Vera lab focuses on drug discovery efforts targeting orphan nuclear receptors (NRs). They have developed and utilized an array of biophysical methods for high-throughput screening of compounds binding the Germ Cell Nuclear Factor (GCNF), which holds great promise to the future of stem cell therapy and the development of anti-sterility drugs for men. Their goal is to identify the endogenous metabolite of orphan nuclear receptors using in-silico molecular docking of compound libraries to orphan NR targets, in tandem with a liquid chromatography-mass spectrometry (LC-MS) metabolomics platform. The deorphanization of NRs could provide crucial clues to the structure of synthetic compounds that would fit the binding pocket. They will use X-ray crystallography to structurally confirm specific binding of drugs and endogenous metabolites to NRs, and NMR spectroscopy techniques to characterize the interaction dynamics. The invaluable structural and dynamics information will aid structure optimization of synthetic compounds for better drug potency and efficacy. They will be working closely with other members of the 91女神-IDBI, including John Tavis, Marvin Meyers, Feng Cao, Maureen Donlin, Lynda Morrison, and Getahun Abate on drug discovery efforts.
Molecular Microbiology and Immunology; Institute for Molecular Virology
duane.grandgenett@health.slu.edu ;
Duane Grandgenett's laboratory has been studying retroviruses since 1970 and discovered the viral integrase (IN) in 1978 in avian retroviruses. IN is responsible for the integration of viral DNA into the host chromosomes. Since the early 1990s, they have focused on HIV-1 IN and helped Merck & Co develop the first major lead inhibitors directed against IN. The first FDA-approved inhibitor, Raltegravir, was in 2007. Two other companies are marketing similar active site inhibitors, one of which (Dolutegravir, GSK) is far superior at the clinical level. Their current efforts are directed towards understanding the mechanisms associated with the assembly of HIV-1 and Rouse Sarcoma Virus (RSV) IN-DNA complexes and their analyses at atomic resolution level. There are no HIV-1 IN-DNA complexes where detailed active site inhibitors can be thoroughly evaluated, except though a very distantly related surrogate prototype foamy virus IN-DNA model. They are now investigating whether the RSV IN-DNA complex can be utilized to study HIV-1 inhibitors at the atomic level. Their recent publications strongly suggest that RSV IN will serve as an excellent surrogate model for HIV-1 IN inhibitors. RSV and HIV-1 IN are similar genetically and structurally and, are equally inhibited in vivo and in vitro by the HIV-1 clinical inhibitors.
Biochemistry and Molecular Biology
sergey.korolev@health.slu.edu;
The Korolev lab studies the mechanism of protein function using X-ray crystallography
combined with biophysical and biochemical methods. They are deciphering atomic resolution
structures to understand the mechanism of protein function under normal conditions,
the effect of disease-related mutations and the mechanism of protein interactions
with ligands, cofactors and inhibitors. They are developing high throughput inhibitor
screening assays for DNA binding and peptide interacting proteins. Systems of interest
include 1) recombination mediator proteins (RMPs) important for genome maintenance,
DNA repair and implicated in cancer and other diseases; 2) DNA helicases involved
in DNA replication and repair; 3) calcium-independent phospholipase critical for inflammation,
calcium homeostasis and implicated in a wide spectrum of diseases from ischemia to
neurodegeneration. They work closely with other members of the 91女神-DDG, including
John Tavis, Duane Grandgenett, and David Griggs.
Biochemistry and Molecular Biology
nicola.pozzi@health.slu.edu;
Pathological activation of the complement and clotting cascades leads to thrombosis
and chronic inflammation, and is linked to the onset and progression of autoimmune
disorders. In Nicola Pozzi's laboratory, they study the unknown biology of complement
and clotting factors, investigate their structure-function relationships, identify
new ligands and define their mechanisms of recognition. Finally, they engineer novel
constructs with the desired functional properties to correct the disease state. To
achieve their goals, they routinely express recombinant proteins from bacteria and
mammalian cells for biophysical (single-molecule fluorescence, DLS, analytical centrifugation,
calorimetry) and structural analysis (X-ray crystallography and SAXS). They develop
and perform kinetic and binding assays based on absorbance, fluorescence and luminescence
spectroscopy, and surface plasmon resonance. The recent development of a novel family
of anticoagulant fusion proteins to ameliorate the outcome of patients suffering from
thrombosis in acute clinical settings such as sepsis and stroke is a representative
example of their work.
Chemistry
Research in the Znosko laboratory focuses on the thermodynamics and structural features of RNA motifs. While sequences of many important RNAs have been determined, little is known about structure-function relationships of RNA. One reason for this lack of information is that there is little definitive secondary and tertiary structural information about RNA. X-ray crystallography and NMR methods are providing an increasing number of RNA structures, but it is unlikely that these methods will keep pace with the rate at which interesting sequences are being discovered. Thus, there is a need for reliable, rapid methods to predict secondary and tertiary structures of RNA. Being able to predict secondary and tertiary structures of RNA provides a foundation for determining structure-function relationships for RNA and for targeting RNA with therapeutics. Therefore one broad, long-term objective of the laboratory is to improve RNA secondary and tertiary structure prediction from sequence.
Biochemistry, Washington University in Saint Louis
Michael Prinsen is a staff scientist within the Department of Biochemistry at Washington University in St. Louis. Prinsen is an active member of the Center for Drug Discovery and the High Throughput Screening Core. He has contributed to numerous projects at the 91女神-IDBI with biological assay development (in vitro and in vivo), screening assay development, and expert analytical chemistry support.Chemistry, Molecular Microbiology and Immunology
Damon Osbourn contributes to many research projects throughout the university. Recent projects have primarily focused in infectious bacteria and parasites, included research on anti-infectives (for cryptosporidium, malaria, and zoonotic staphylococci), and development of drug resistance.Pius XII Memorial Library
megan.toups@slu.edu; University Libraries
Megan Toups is the STEM librarian in the Research and Instruction Services Department at Pius XII Memorial Library at 91女神. She works with the College of Arts and Sciences and the School of Science and Engineering to connect students, faculty and staff with library resources and services. Her work supports undergraduate and graduate education, student and faculty research, and faculty teaching. She has done lab research in the biological sciences including work for Steve A.N. Goldstein, Ph.D., studying ion channels. In addition to supporting students and university faculty research and learning, her own faculty service, interests, and scholarship are focused on information literacy education; data management; copyright; and invisible disabilities in higher education.
Chemistry
malkanthi.karunananda@slu.edu;
Research in the Karunananda Lab strategically leverages a combination of synthetic inorganic, organometallic, and computational chemistry techniques to solve pressing challenges in catalysis. The overall research theme is built on employing multiple metals and/or multiple ligands to synergistically bring about novel reactivity and selectivity. A special focus is placed on interrogating reaction mechanisms through experimental and computational techniques to predict and design novel catalysts.
Current projects in the lab include photosensitizer development using earth-abundant metals with target applications in organic synthesis and photodynamic therapies, and organometallic catalyst development for polymer upcycling. The experimental work in the lab focuses on multi-metallic complex synthesis, characterization and catalytic reaction development. The computational work in the lab focuses on photoreactivity and catalyst optimization with DFT calculations, statistical analysis, and machine learning approaches.
Chemistry
premila.russell@slu.edu; Website
Research in the Samuel Russell Lab centers on applying computational chemistry methods to build and simulate atomistic models of human cell environments. Using these "cells-on-computers", they aim to address the current challenges in characterizing "hidden states" of biomolecules within the complex cell environments that arise from limitations of spatial-temporal resolutions of traditional experiments and in silico methods. Characterizing biophysical properties, especially at the atomic level, of such biomolecular states can lead to health advances. Samuel Russell's long-term focus is to combine these cells-on-computers technology with complementary experimental approaches to develop streamlined platforms for both investigating structural mechanisms of cell-specific human diseases and screening drugs in a rapid and cost-effective manner. Current focuses of projects in their research program include mechanisms of red blood cell diseases, which can lead to cardiovascular complications, and metabolic pathways in cancer cells.
Internal Faculty Advisors
Biology - Retired; Adjunct
Jack Kennell is interested in mitochondrial genomics, intracellular communication pathways, mobile genetic elements and evolution in fungi. He primarily studies filamentous fungi (Neurospora and Fusarium spp.), but has worked with a variety of both ascomycete and basidiomycete yeasts and is part of Malassezia consortium. He has conducted two projects that involved the assessment of anti-microbial agents: 1) antibacterial effectiveness of silver and zinc compounds in polyurethane rubber compounds (such as flooring products), and; 2) mode of action of zinc pyrithione (the active ingredient in many anti-dandruff shampoos). He has developed some relatively simple and reliable assays that can be conducted in micro-titer plates and carried out by undergraduate students, and also has a collection of Neurospora mutants that can provide insight into whether the anti-fungal properties relate to inhibiting mitochondrial function.
Molecular Microbiology and Immunology -Retired; Emeritus
David Griggs' laboratory specialized in drug discovery and the translation of basic discoveries to therapeutic applications. Dave is an expert in assay development and optimization for high-throughput screening of compounds, assessment of target potency and selectivity for lead characterization, and in vitro and in vivo assessment of compound pharmacokinetics and metabolism (ADME). The lab discovered and the development of a small-molecule compound series towards an effective treatment to reduce or reverse the destructive organ fibrosis that occurs in many disease conditions. They also developed new medicines for tuberculosis, cryptosporidiosis and bone disorders.
Pediatrics
adriana.montano@health.slu.edu;
Adriana Monta帽o, Ph.D., is an expert in the study and development of therapies for mucopolysaccharidosis (MPS), a set of rare diseases affecting bone, musculoskeletal and organ development. Her discoveries include potential therapies for MPS IVA. Her work is extensive, working on multiple facets of Morquio disease. She has contributed to the development of clinical repositories, enabling discovery and diagnostic research, improvement of diagnostic and childhood screening protocols and assays, as well as extensive research improving enzyme replacement therapy by protein and delivery optimization. Monta帽o has also collaborated with multiple industry partners to study other lysosomal storage and bone disorders.
Pharmacology and Physiology
gina.yosten@health.slu.edu; Website
Gina Yosten, Ph.D., has developed novel screening methods to match formerly 鈥榦rphan鈥� G-protein coupled receptors (GPCRs) to their cognate ligands, an important step in identifying their role in biologic and disease processes. She is using these findings to study the role of GPCRs in diabetes-associated microvascular dysfunction and in central circuits underlying obesity-associated hypertension.
Chair, Department of Pharmacology and Physiology
Director, Institute for Translational Neuroscience
Fellow, Academy of Science, St. Louis
Fellow, National Academy of Inventors
daniela.salvemini@health.slu.edu; Website
Daniela Salvemini is the William Beaumont Professor and Chair of the Department of Pharmacology and Physiology, and the director of the Institute for Translational Neuroscience. Salvemini focuses her work on the discovery and development of therapeutics for non-opioid pain relief. Using multi-disciplinary approaches including genetic, molecular, and pharmacological tools, her lab studies how neuro-inflammatory process impact periphery and CNS during chronic pain. Her discoveries in adenosine A3 receptor signaling pathway have been licensed to BioIntervene, which she helped found. Salvemini is a Fellow of the Saint Louis Academy of Science, and a Fellow of the National Academy of Inventors.