University of California
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University of California
After completing dual B.S. degrees in chemistry and recombinant gene technology from SUNY Fredonia, Dr. Gestwicki performed his Ph.D. thesis work at the University of Wisconsin with Professor Laura Kiessling on the mechanisms of multivalent receptor-ligand interactions. Using innovative chemical tools, Gestwicki and Kiessling uncovered a key role for dynamic receptor-receptor interactions during bacterial sensing. This work sparked Dr. Gestwicki's interest in using the methodologies of synthetic chemistry to address fundamental problems in biology - especially those that have proven difficult to answer using other strategies.
Dr. Gestwicki continued work in the area of Chemical Biology in the laboratory of HHMI investigator Gerald Crabtree at Stanford University. There, he teamed with Crabtree and Isabella Graef to develop a new method for inhibiting protein-protein interaction. The primary innovation in this method is that the cell's own proteins are recruited by the organic molecule to assist in the process. Thus, the "inhibitory complex" is a combination of a drug-like chemical and an endogenous protein.
In 2005, Dr. Gestwicki joined the faculty of the University of Michigan. There laboratory continued to study new ways of using synthetic molecules. The group's biological interest are focused on understanding how the body normally protects intself from neurodegenerative disorders, such as Alzheimer's disease, so that they can develop ways of boosting these favorable pathways.
Dr. Ahn obtained her PhD in Pharmacology in 2007 from University of Washington under the supervision of Dr. William A. Catterall and then pursued postdoctoral studies under the guidance of Dr. Stanley Prusiner at UCSF. She worked with Dr. Stephen DeArmond after her postdoctoral training and, in March 2012, Dr. Ahn was appointed as an Assistant Adjunct Professor.
Dr. Ahn's research focuses on developing therapeutics for prion diseases and related human neurodegenerative disorders such as Alzheimer’s disease via multi-therapeutic approaches. Dr. Ahn is interested in understanding the mechanisms and molecular basis of prion biology and neuronal repair in order to find novel targets for therapeutic development. In addition, she is interested in developing proper cell culture systems to screen effective drug candidates for neurodegenerative disease.
The DeGrado Research Group focuses on small molecule and protein design as an approach to understanding macromolecule structure and function. The DeGrado group's primary research interest is in the de novo design, in which one designs proteins beginning from first principles. This approach critically tests our understanding of protein folding and function, while also laying the groundwork for the design of proteins and biomimetic polymers with properties unprecedented in nature. The de novo design of proteins has proven to be a useful approach for understanding the features in a protein sequence that cause them to fold into their unique three-dimensional structures. In addition, it has been possible to design functionally interesting proteins, which bind redox-active cofactors, DNA, and transition metals. Finally, this approach has been extended to the design of membrane-active proteins, including ion channels, antibiotics and fusogenic agents.
The DeGrado Research Group also studies the structure and function of a number of pharmacologically interesting systems. The DeGrado group is determining the structure of the M2 proton channel from influenza A virus, and its mode of inhibition by various channel-blocking drugs. In collaboration with Joel Bennett (Department of Medicine), we study the mechanism of signal transduction of integrins such as ?II?b3, with a particular focus on the role played by the membrane-spanning regions of this protein. We have developed small molecule mimics of integrins and the platelet collagen receptor, gpVI. Finally, the DeGrado group developed a number of small molecule mimics of antimicrobial host defense proteins, which show considerable promise for treating antibiotic-resistant infections.
Dr. Watts obtained his PhD in Laboratory Medicine and Pathobiology in 2008 from The University of Toronto under the supervision of Dr. David Westaway and Dr. Gerold Schmitt-Ulms and then pursued postdoctoral studies under the guidance of Dr. Stanley Prusiner at UCSF. In July 2012, Dr. Watts was appointed as an Assistant Adjunct Professor within the Institute for Neurodegenerative Diseases.
The research interests of Dr. Watts include the prion diseases and related human neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. His research focuses on developing transgenic mouse and cellular models of neurodegenerative diseases that can be used to study the biology of these illnesses and as tools for developing novel therapeutics. In particular, Dr. Watts is interested in understanding the mechanisms of spontaneous prion formation in sporadic Creutzfeldt-Jakob disease, the molecular basis of prion strains, the function of the cellular prion protein, and the prion-like properties of Aβ and tau aggregates. He is also interested in emerging neuroimaging paradigms and has been heavily involved in developing bioluminescence imaging models for monitoring neurodegeneration in live mice.
Dr. Stöhr is investigating the structural basis for self propagation of distinct protein conformations in prion diseases. His main focus is the induction of the prion state in vitro to form synthetic prions which display self propagation in vivo. The formation of prions made of recombinant proteins represents the basis for producing prions in sufficient amounts for structural studies. Once formed, these prions are structurally characterized by a variety of biochemical and biophysical methods (e.g., electron microscopy and solid state NMR). Most recently Dr. Stöhr was able to show that misfolded synthetic A-beta peptides alone are sufficient to self propagate in vivo and hence belong to disease-associated proteins which can be present in a prion state.
Dr. Gever has a national reputation for research in neuroscience, biochemical pharmacology and the application of high-throughput screening (HTS) and related disciplines to accelerating the process of drug discovery. Prior to joining the IND, Dr. Gever was a Senior Scientist at Roche Pharmaceuticals. Dr. Gever is the supervisor of the IND’s HTS team.
Emeritus Professor, Department of Neurology
Dr. Ramsay is a Professor of Neurology, the Associate Director of the IND and the former President of the University of Maryland, Baltimore. He contributes his expertise as a blood-brain barrier researcher on all aspects of the IND's research.