Associate Professor
Department of Medicinal Chemistry, Lee Lab, Medicinal Chemistry Faculty, School Faculty
Telephone: (206) 616-3972
Email: kklee@uw.edu
Website: Lab website
Expertise: Infectious Diseases, Mechanisms-of-Drug-Interactions, Vaccines and VirologyOur lab uses complementary structural and biophysical methods to characterize the conformational changes viruses carry out in order to invade host cells. We focus on the transitions and the critical functional states that often are too transient or dynamic to characterize by classical structural methods. Understanding these events is essential to understanding mechanisms of cell entry, for understanding the activity of neutralizing antibodies, and also for developing novel antivirals that can target the virus prior to infection. Our core expertise is in using Hydrogen/Deuterium-Exchange Mass Spectrometry (HDX-MS), cryo-electron microscopy (cryo-EM) and small-angle X-ray scattering (SAXS) to monitor conformational change of protein complexes and viruses. An NIH K99/R00 Career Award supported my transition to studying influenza virus with techniques such as cryo-electron tomography and SAXS. Current projects apply cryo-ET, SAXS, and HDX-MS to dissect the spring-loaded membrane fusion mechanism of influenza virus hemagglutinin (HA) and HIV Env.
For example, in recent studies using cryo-ET and HDX-MS, for the first time we have been able to visualize the nature of fusion protein-mediated membrane remodeling and to determine the sequence of events in whole viruses and isolated fusion proteins that are needed to produce efficient fusion.
With the support of a Center for AIDS Research Creative and Novel Ideas in HIV Research (CNIHR) award for new investigators and with Gates Foundation support, my lab is working with Shiu-Lok Hu’s group (Pharmaceutics) to investigate the structural basis for antigenicity and immunogenicity of HIV Env glycoproteins. In addition, we have been able to characterize isolate-specific structural differences and their impact on antigenicity of Env; these effects are difficult to study by conventional approaches. Our biophysical approaches have also enabled us to analyze CD4 receptor, entry inhibitors, and neutralizing Abs in complex with the native-like HIV Env trimers. In collaboration with Julie Overbaugh’s group at the Fred Hutchinson Cancer Research Center, we are gaining insight into the nature of Env-dependent HIV transmission and the development of neutralizing antibodies in response to infection.
Dr. Lee also holds an adjunct appointment in the UW Microbiology Department and is a member of a number of cross-departmental graduate programs including the Biological Physics Structure and Design Program, the Pathobiology Graduate Program and the Molecular and Cellular Biology Program.
Shirley is a Seattleite, born and raised. From a young age, she dedicated her life to advocating for women, children, human rights and healthcare. Her Mother and a knack for science lead her to Pharmacy school, where she thrived. Her career helped so many people, but as the HIV/AIDS epidemic grew, it became a central part of her career. Her outreach efforts, where she went door to door to help people understand the disease, was only part of her contribution to battle the epidemic. She was a founding board member of AIDS Housing of Washington (recently renamed Building Changes) and co-chaired the $8.5 million campaign that built the group’s Bailey-Boushay House in 1992. Her legacy of advocating for women pharmacists lives on with the Herb and Shirley Bridge Endowed Professorship, designed to support women in pharmacy.
Dr. Hall joined the faculty of the School of Pharmacy in 1952, after spending a few years at the Eli Lilly and Co. as a Pharmaceutical Chemist. After returning to the UW, he soon set himself apart from his peers by developing innovative approaches to teaching, particularly in dispensing pharmacy. While at UW Hall developed one of the first models for an externship program, allowing senior pharmacy students to gain theoretical and practical experience in a pharmacy setting for academic credit. Being too ahead of his time, this for credit externship program did not became a formal requirement in the School of Pharmacy’s curriculum until the 1990’s, thanks in large part to Dr. Hall’s vision. Dr. Hall was also awarded the Distinguished Alumnus Award in 1980 to celebrate the impact of his career on the profession of Pharmacy.
After completing his graduate work in California, Sid Nelson returned to the School of Pharmacy to join the faculty in 1977. Progressing through the ranks, he landed his “dream job” as the Dean of the School of Pharmacy in 1995. Under his leadership, the School converted our degree offerings from a B.S. degree to an entry-level Doctor of Pharmacy degree program and added a nontraditional approach that enabled existing pharmacists to obtain the Pharm.D. degree. He also evolved the graduate programs and worked tirelessly to expand the School’s faculty. In 2008, he returned full-time to his research and teaching activities in the School’s Department of Medicinal Chemistry. Sid truly embodies the idea of a legend with his warmth, care and passion for our students and alumni.
Jonathan Watanabe, ‘98, ‘08, ‘12, PharmD, MS, PhD, BCGP, is a board-certified geriatrics pharmacist, outcomes researcher, and associate professor at the University of California San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences. Dr. Watanabe was the first the UW/Allergan Global Health Economics and Outcomes Research Fellow. His research on the cost of non-optimized therapy, comprehensive medication management and drug prices has been cited in successful state legislative efforts for pharmacist provider status. Dr. Watanabe is an inaugural scholar in the National Academy of Medicine Emerging Leaders in Health and Medicine program.
Timothy Fuller, ‘69, is an independent pharmacist consultant and founder of Timothy S. Fuller & Associates, Inc. Consulting. He is recognized as the Father of Pharmacist Collaborative Drug Therapy for his extensive and continued research, advocacy, and publication on the subject. In partnership with the WSPA and PATH, Tim recruited 50 pharmacies in Washington to pilot the U.S. movement for pharmacists to prescribe emergency contraceptive pills. Tim is the fourth member of the UW School of Pharmacy B.S. Class of 1969 to receive a PAA Distinguished Alumni Award.