Heritage of the CWRU Department of Pharmacology Earl W. Sutherland, Jr Discovery of Cyclic AMP Ferid Murad Nitric Oxide Signaling Nobel Prize Alfred G. Gilman G-protein Signal Transduction Continuing Tradition of Excellence in Pharmacology at CWRU First high resolution structure of a G-protein coupled receptor (GPCR) • most common target of modern drug development In the top five of most highly cited articles in Biology / Biochemistry Thomas Reuters Survey Kris Palczewski, Chairman of Pharmacology Molecular Therapeutics Training Program ( MTTP ) Membrane Translational Structural Biology Therapeutics & Pharmacology The NIH-funded Molecular Therapeutics Training Program (MTTP) involves faculty from six major research centers in Cleveland Cellular / - CWRU, UniversityMolecular Hospitals, Case BiologyCenter, & Comprehensive Cancer Cleveland Research Clinic Foundation, Cleveland VA Medical Rotations Center, and MetroHealth Medical Center. Students enter the Pharmacology Graduate Program directly, or via the Biomedical Molecular Sciences Training Program (BSTP)Pharmacology or the Cancer Sciences Training Program (MSTP). Medical & Cell Therapeutics Regulation Core and Advanced Tracks The MTTP provides students with outstanding training in the cellular, molecular, and physiological basis for therapeutics, preparing them for independent careers in research and teaching in a variety of academic or industrial settings. Molecular Therapeutics Training Program ( MTTP ) Membrane Structural Biology & Pharmacology Translational Therapeutics The Molecular Pharmacology and Cellular RegulationTrack promotes Cellular / common research interests in Molecular Biology &of drug actions molecular mechanisms Research that are and regulatory processes potential targets Rotations for drug development. Cancer Therapeutics Core and Advanced Tracks Molecular Pharmacology & Cell Regulation The MTTP provides students with outstanding training in the cellular, molecular, and physiological basis for therapeutics, preparing them for independent careers in research and teaching in a variety of academic or industrial settings. Molecular Pharmacology and Cellular Regulation Track Andrea Boyd-Tressler and George Dubyak • Novel role of ATP as a chemoattractant that facilitates the immune component of the anti-tumor response associated with cancer chemotherapy … Luke Bury and Shasta Sabo • Modern electrophysiology and imaging used to discover the mechanisms by which nerve synapses are formed in the developing brain - discovering the basis for autism … Meghana Gupta and Danny Manor • Learning how phosphorylation of tyrosine residues affects the biochemical and physiological activities of proteins that regulate G-protein signaling – discovering anti-cancer targets … Molecular Therapeutics Training Program ( MTTP ) Membrane Structural Biology & Pharmacology Translational Therapeutics Benefiting from the Case Comprehensive Cellular / Cancer Center, the Cancer Therapeutics Track fosters Molecular common interest in the Biology & concepts of cancer biology that form the Research basis for specific therapeutic strategies. Rotations Cancer Therapeutics Core and Advanced Tracks Molecular Pharmacology & Cell Regulation The MTTP provides students with outstanding training in the cellular, molecular, and physiological basis for therapeutics, preparing them for independent careers in research and teaching in a variety of academic or industrial settings. Cancer Therapeutics Track Chris Ryder Clark Distelhorst • Studies of mechanisms of regulation of lymphocyte apoptosis via the TDAG8 G protein-coupled receptor in the context of leukemia.… MollyTaylor Billl Schiemann • “The role of the microenvironment in mediating breast cancer progression. Specifically I'm interested in the role of microRNAs on TGF-beta mediated-metastatic progression…” Molecular Therapeutics Training Program ( MTTP ) Membrane Structural Biology & Pharmacology Translational Therapeutics The Translational Therapeutics Track Cellular / interfaces basic science trainees with Molecular physician-scientists Biology &around a common interest in developing Research / improving the Rotations use of therapeutic agents in a rational and individualized manner. Cancer Therapeutics Core and Advanced Tracks Molecular Pharmacology & Cell Regulation The MTTP provides students with outstanding training in the cellular, molecular, and physiological basis for therapeutics, preparing them for independent careers in research and teaching in a variety of academic or industrial settings. Translational Therapeutics Track Michele Mumaw Marvin Nieman • Antiplatelet therapeutics…”my project examines an agent that has ideal characteristics; it delays thrombosis but does not influence bleeding time…” Peter Levitt Robert Bonomo • Structure function studies of Class A beta-lactamases. Understanding the factors that permit the successful evolution of beta-lactamases in the clinic… Amar Desai Stan Gerson • “I study the role of DNA repair in hematopoietic stem cells to understand the relationship between DNA repair, cell cycle status, and hematopoietic stem cell function.…” Structural Biology & Pharmacology Track … Understanding the function of telomerase in DNA replication pertaining to aging and cancer chemotherapy Mike Mullins Derek Taylor Studying the molecular dynamics of Drp 1 in mediating mitochondrial fission & fusion pertinent to neurodegenerative diseases Jason Mears Chris Francy Determining the structure of isolated discs from the rod cells of the eyes of mouse models of human eye diseases Neetu Gulati Phoebe Stewart Director, CCMSB Cleveland Center for Membrane and Structural Biology Center for Membrane Cleveland CenterCleveland for Membrane and Structural Biology and Structural Biolo CCSMB is a joint venture between Case Western Reserve University and Cleveland Clinic CCMSB is adminstratively overseen by the Department of Pharmacology (http://ccmsb.case.edu) Electron Microscopy NMR embrane and Structural Biology Cleveland Center for Me The Electron Microscopy facility features a high-end 200 kV cryo-electron microscope for high-resolution imaging of single complexes and 2D crystals. A 120 kV EM is used for sample screening and conventional imaging of sections The NMR facility is well equipped with state of the art and negatively stained samples. ranging from 600 to 900MHz. Two Bruker 600, an 800 and a X-ray generator Crystal robot NMR instrumentat 900 MHz are equip with cryogenic probes for solution NMR work. The 800MHz instrument can also switched to solid state operation. Mass spec, computational modeling, one of the 3 largest, best equipped facilities in the world!