The Pharmacology department has a proven track record of producing academic and industrial leaders in biomedical research throughout the country and world. Our gifted faculty are engaged in cutting-edge research spanning many areas including:
- Chemical biology
- Clinical Pharmacology
- Electrochemical sensors
- Drug Metabolism
Exploiting biology-inspired electrochemical sensing to study the fate of molecules in the body.
Our laboratory focuses on the development of electrochemical biosensors for the continuous detection of small, physiologically-important molecules in vivo. We pursue this by studying the biophysical interactions between receptors and targets, developing signal transduction mechanisms to produce electrical readouts, and by designing and fabricating devices to be directly implanted in the body. Using these we address questions in drug pharmacokinetics and pharmacodynamics, toxicology and metabolism. Our overreaching goals are the development of platforms to achieve metabolism-responsive drug delivery and diagnostic devices for personalized health care.
Drug discovery for disorders of neurodevelopment.
The research group is a laboratory focused on medicinal chemistry and drug discovery, primarily addressing diseases of neurodevelopment such as schizophrenia. The lab is engaged in the design and synthesis of molecules for a given biological target, analysis of in vitro and in vivo results, as well as further refinement through multiple cycles of synthesis and testing. The resulting advanced leads will have good potency and selectivity for the target of interest, and will be used to test biological hypotheses both in vitro and in vivo to determine if modulating the target is indeed a viable therapeutic strategy. By executing on medicinal chemistry programs, we will drive translational science from target and pathway
Drug Metabolism and preclinical drug development; small molecule mass spectrometry; targeted metabolomics; antiviral drug-induced toxicity; modulation of cellular signaling pathways by reactive metabolites.
The Bumpus laboratory applies mass spectrometry-based proteomics, metabolomics, imaging and molecular techniques to understand mechanisms underlying interindividual variability in drug outcomes, including toxicities. In doing so we define the metabolism of clinically relevant drugs while elucidating the impact that drugs and their metabolites have on cellular signaling. Our work employs in vitro and preclinical in vivo models, as well as the analysis of clinical samples. The overarching goal of our work is to integrate mechanistic understanding of drug metabolism, the impact of drug metabolites on cellular pathways, and 3-dimensional distribution of drugs in cells and tissues to facilitate the personalization of medicine.
Preclinical models of neurological and psychiatric disorders.
Psychiatric disorders and related neurodevelopmental disorders result from the complex interaction of multiple genetic and environmental risk factors. Our laboratory uses rodent models to determine how these risk factors modulate neurobiology and behavior. We utilize neurochemical, electrophysiological, and behavioral assays to interrogate the neural systems thought to be impaired in neurodevelopmental disorders. Our ultimate goal is to use this knowledge to inform drug discovery efforts designed to increase and improve the treatment options available for central nervous system disorders.
Chemical biology and molecular biology; use of small molecules as probes to elucidate mechanisms of signal transduction; angiogenesis and cell proliferation.
Our primary research interest lies at the interface between chemistry, biology and medicine. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active compounds are identified, they will serve as both probes of the biological processes of interest and leads for the development of new drugs for treating human diseases.
Organic and medicinal chemistry, chemical biology: drug delivery; study of non-mammalian isoprenoid biosynthesis; development of potential therapeutic agents for cancer and infectious disease.
The Freel Meyers lab applies organic synthesis, chemical biology, and enzymology to design novel anti-infective approaches. One research area focuses on developing strategies to selectively inhibit enzymes in the essential bacterial MEP pathway to isoprenoids. In addition, we study the mechanism and function of DXP synthase, the first enzyme in this pathway and critical branch point enzyme in bacterial metabolism, to understand its metabolic roles during infection. We also bring our expertise in small molecule synthesis and prodrug development to a multi-institutional collaboration to invent novel long-acting nanoformulations of clinically-used anti-retrovirals toward a goal to increase adherence and success of life-long HIV treatment.
Redox signaling in aging and neurodegeneration.
Redox regulation plays a central role in signal transduction processes operating in the cell. Disruption of redox signaling is a hallmark of several neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Ataxias. It is becoming increasingly clear that redox imbalance contributes to disease progression and pathophysiology of these diseases.
My laboratory studies the molecular mechanisms underlying redox homeostasis in the brain with a focus on signaling mediated by gaseous messenger molecules such as hydrogen sulfide (H2S) and nitric oxide (NO). H2S and NO signal via post-translational modifications, on reactive cysteine residues, termed persulfidation/sulfhydration and nitrosylation respectively. Using cell culture, mouse models and patient samples, we have shown that modulating sulfhydration and nitrosylation networks have therapeutic benefits. These studies have yielded important clues that may be harnessed to develop novel therapeutics that delay, halt, reverse or better still, prevent neurodegeneration.
Cellular regulation by glycans in the nervous and immune systems.
Cell-cell recognition occurs when complementary molecules on opposing cell surfaces meet. A receptor on one cell surface binds to its ligand (counter-receptor) on a nearby cell, initiating a cascade of events that regulate cell behaviors ranging from simple adhesion to complex cellular differentiation to cell death. Glycans (glycoproteins, glycolipids, proteoglycans) richly decorate all cell surfaces, and represent the most prominent class of cell surface molecules. Members of this large and varied family are ligands for complementary binding proteins, lectins, on nearby cells. Lectin-carbohydrate interactions mediate cell-cell interactions throughout the body. The study of cell surface glycans, lectins, and their roles in cell physiology are part of the rapidly expanding field of glycobiology. The Schnaar lab studies the functional roles of glycans in immunoregulation and in nerve cell function.
Structural and Chemical Biology of Uracil Metabolism and Applications to Cancer Therapy, Innate and Adaptive Immunity.
My lab is interested in how immune cells alter cellular dNTP pools to thwart viral infection. We also study the role of dNTP metabolism in driving mutagenesis, cell senescence and cancer. This area of cell metabolism is rich in new drug targets.
Histone and chromatin modifications, epigenetics and gene function, identification of histone binding modules, and small RNA directed gene silencing.
The Taverna laboratory studies the mechanistic links between epigenetic histone modifications and disease using biochemistry, high-throughput sequencing, and mass spectrometry approaches in a variety of model organisms ranging from mammals, to ciliates and yeast. We have characterized how proteins which “read”, “write”, and “erase” histone modifications orchestrate interpretation of the genome, as well as how they are linked to a wide variety of health issues and diseases, including cancer.
Signal Transduction; protein network; host-pathogen interaction; biomarker identification.
The Zhu lab develops and applies high-throughput technologies to understand the molecular principles at the systems biology level. We have constructed the world-largest human protein array (i.e., HuProt) and are using it for both basic and clinical research. To deal with multipass transmembrane proteins, the Zhu Lab recently invented Virion Display (VirD) technology that provides membrane environment to maintain correct conformation and function of hundreds of human GPCRs. Using these cutting edge technologies, the Zhu Lab has made significant contribution to signaling network construction, epigenetic regulation of transcription, pathogen-host interactions, and biomarker discovery and validation.
Jed Fahey, Sc.D., Assistant Professor (Secondary)
Phytochemistry/ nutrition-based prevention of chronic disease
Craig A. Townsend, Ph.D., Professor
Organic and bioorganic chemistry: biosynthesis of natural products and biomimetic synthesis.
Huijun Wei, Ph.D., Assistant Professor (Secondary)
Identifying and validating drug targets for the treatment of neurodevelopmental disorders.
Philip A. Cole M.D., Ph.D., Professor (Adjunct)
Albena Dinkova-Kostova, Ph.D., Professor (Adjunct)
Wade Gibson, Ph.D., Professor Emeritus (Primary Appointment)
Gary S. Hayward, Ph.D., Professor (Secondary Appointment)
Cyrus Khojasteh, Ph.D., Professor (Adjunct)
Mark A Schenerman, Professor (Adjunct)
Johannes N. van den Anker, M.D., Ph.D., Professor (Adjunct)
Amina S. Woods, Ph.D., Professor (Adjunct)