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Winter 2024 – Dean’s Distinguished Lecture
February 28 @ 11:00 AM – 1:00 PM
Please arrive 15 minutes prior to the event for registration. Light lunch hors d’oeuvres and beverages will be available during the reception from 12 to 1 p.m.
Designing Drugs for Human Diseases Using Structural Biology
About the Lecture
This lecture will discuss how structural biology provides the required information for designing specific therapeutic agents and will present a few specific examples of potential drugs designed here at UCI targeting neurodegenerative diseases and melanoma. In addition, included will be an example of a UCI industrial collaboration that led to important insights into how certain HIV antiviral drugs work.
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A majority of drugs are targeted to specific proteins. Proteins are large complex molecules consisting of thousands of atoms while most drugs are much smaller consisting on the order of dozens of atoms. Enzymes, the engines of life that catalyze all chemical transformations in biology, are proteins that form highly ordered three-dimensional structures. One region of the structure that carries out the required transformations is called the active site. Binding of a drug to the active site can prevent the enzyme from carrying out its normal function. For example, certain antibiotics bind to bacterial enzyme active sites to block their activity thereby preventing infection or growth/proliferation. Knowing the detailed three-dimensional structure of the protein can greatly streamline the process of designing novel drugs that specifically bind to the active site.
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About Distinguished Professor Thomas Poulos
Thomas Poulos PhD is a Distinguished Professor of Molecular Biology and Biochemistry at the University of California, Irvine. He has had an illustrious career in both the private sector and academia
Click here to read more about Professor Poulos background…
During his graduate years (1968-1972) in the Dept. of Biology at UCSD Prof. Poulos studied nuclease mechanisms in the lab of Prof. Paul Price. Realizing that to understand enzyme function, one must know structure, he moved to Joe Kraut’s lab in the Dept. of Chemistry at UCSD to learn protein crystallography. Prof. Poulos first studied transition state analogs bound to the serine protease, subtilisin. He then solved the first heme enzyme structure, cytochrome c peroxidase, and initiated the early work on cytochrome P450cam. During this time he secured NSF support for both the CCP and P450 work. In 1983 Prof. Poulos was recruited by Genex Corp., a relatively new biotechnology company in Maryland. He first held the title of Principal Research Scientist and in 1985 became the Director of Protein Engineering. During this period Genex solved the structure of some industrially important enzymes, developed proteases of enhanced stability that have been used commercially, and developed what has come to be called single-chain antibodies. The structure of the first P450 (supported by NIH) was solved during this period. After 4 years at Genex, Prof. Poulos returned to academia and in 1987 he accepted the position of Director and Professor of Chemistry at the University of Maryland’s Center for Advanced Research in Biotechnology or CARB. CARB started with a small administrative staff of 3 and one technician. Over the next 4 years Prof. Poulos oversaw the development of CARB to a total staff of 60 including University of Maryland faculty and faculty from the National Institute of Science and Technology, the University’s partner in the development of CARB. In 1991 he received the Presidential Meritorious Service Award from the University of Maryland.
In 1992 Prof. Poulos moved to UCI where he initiated work on nitric oxide synthase which, in collaboration with Prof. Richard Silverman at Northwestern, has led to the development of the most potent isoform-selective inhibitors of neuronal nitric oxide synthase inhibitors yet developed. These inhibitors exhibit exceptional in vivo neuroprotection in animal model systems. In 2004 he won the Brodie Award in drug metabolism from the American Association of Pharmacology and Experimental Therapeutics and 2014 the Gordon Hammes American Chemical Society Biochemistry Lectureship and has given several named lectures. Prof. Poulos has served as a member and Chair of various NIH and NSF review panels and served on the NCI Board of Scientific Counselors. He has held various leadership positions including Director of the Program in Pharmaceutical Sciences, Director of the Irvine Research Unit in Structural Biology, and Co-Director of the Chemical and Structural Biology Program in the Chao Family Comprehensive Cancer Center. He currently serves on the Stanford Synchrotron Radiation Lab Advisory Committee. As of Feb. 2021, Prof. Poulos has published over 300 papers/reviews.