Kelly Lee
Associate Professor, Medicinal Chemistry
Department of Medicinal Chemistry, Lee Lab, Medicinal Chemistry Faculty, School Faculty
Telephone: (206) 616-3972
Email: kklee@uw.edu
Website: Lee Lab
Education
- AB (Honors), Harvard University
- PhD, Johns Hopkins University
Research Interests
- HIV, Influenza A virus
- Biophysical, structural, and biochemical techniques including X-ray scattering, cryo-electron microscopy, hydrogen/deuterium-exchange mass spectrometry, and fluorescence microscopy to understand the function of viral machinery
Biography
Our 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.
Recent Publications
- Prebiotic amino acids bind to and stabilize prebiotic fatty acid membranes. Cornell CE, Black RA, Xue M, Litz HE, Ramsay A, Gordon M, Mileant A, Cohen ZR, Williams JA, Lee KK, Drobny GP, Keller SL. Proc Natl Acad Sci U S A. 2019 Aug 12. pii: 201900275. doi: 10.1073/pnas.1900275116. [Epub ahead of print]
- Deep Mutational Scan of the Highly Conserved Influenza A Virus M1 Matrix Protein Reveals Substantial Intrinsic Mutational Tolerance. Hom N, Gentles L, Bloom JD, Lee KK. J Virol. 2019 Jun 14;93(13). pii: e00161-19. doi: 10.1128/JVI.00161-19. Print 2019 Jul 1.
- De novo design of tunable, pH-driven conformational changes. Boyken SE, Benhaim MA, Busch F, Jia M, Bick MJ, Choi H, Klima JC, Chen Z, Walkey C, Mileant A, Sahasrabuddhe A, Wei KY, Hodge EA, Byron S, Quijano-Rubio A, Sankaran B, King NP, Lippincott-Schwartz J, Wysocki VH, Lee KK, Baker D. Science. 2019 May 17;364(6441):658-664. doi: 10.1126/science.aav7897.
- Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage. Simonich CA, Doepker L, Ralph D, Williams JA, Dhar A, Yaffe Z, Gentles L, Small CT, Oliver B, Vigdorovich V, Mangala Prasad V, Nduati R, Sather DN, Lee KK, Matsen Iv FA, Overbaugh J. Nat Commun. 2019 May 16;10(1):2190. doi: 10.1038/s41467-019-09481-7.
- Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus. Marcandalli J, Fiala B, Ols S, Perotti M, de van der Schueren W, Snijder J, Hodge E, Benhaim M, Ravichandran R, Carter L, Sheffler W, Brunner L, Lawrenz M, Dubois P, Lanzavecchia A, Sallusto F, Lee KK, Veesler D, Correnti CE, Stewart LJ, Baker D, Loré K, Perez L, King NP. Cell. 2019 Mar 7;176(6):1420-1431.e17. doi: 10.1016/j.cell.2019.01.046.
- Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry. Benhaim M, Lee KK, Guttman M. Protein Pept Lett. 2019;26(1):16-26. doi: 10.2174/0929866526666181212165037. Review.
- Influenza Virus-Liposome Fusion Studies Using Fluorescence Dequenching and Cryo-electron Tomography. Gui L, Lee KK. Methods Mol Biol. 2018;1836:261-279. doi: 10.1007/978-1-4939-8678-1_13.
- Single-Molecule Analysis of a Viral Fusion Protein Illuminates a Fusion-Active Intermediate State. Benhaim M, Lee KK. Cell. 2018 Aug 9;174(4):775-777. doi: 10.1016/j.cell.2018.07.026.
- Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, Moody MA, Verkerke HP, Myles A, Willis E, LaBranche CC, Montefiori DC, Lobby JL, Saunders KO, Liao HX, Korber BT, Sutherland LL, Scearce RM, Hraber PT, Tombácz I, Muramatsu H, Ni H, Balikov DA, Li C, Mui BL, Tam YK, Krammer F, Karikó K, Polacino P, Eisenlohr LC, Madden TD, Hope MJ, Lewis MG, Lee KK, Hu SL, Hensley SE, Cancro MP, Haynes BF, Weissman D. J Exp Med. 2018 Jun 4;215(6):1571-1588. doi: 10.1084/jem.20171450. Epub 2018 May 8.
- Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire. Williams KL, Wang B, Arenz D, Williams JA, Dingens AS, Cortez V, Simonich CA, Rainwater S, Lehman DA, Lee KK, Overbaugh J. Cell Rep. 2018 Apr 17;23(3):682-691. doi: 10.1016/j.celrep.2018.03.082.
- Probing Structural Variation and Dynamics in the HIV-1 Env Fusion Glycoprotein. Munro JB, Lee KK. Curr HIV Res. 2018;16(1):5-12. doi: 10.2174/1570162X16666171222110025. Review.
- Dissection of Epitope-Specific Mechanisms of Neutralization of Influenza Virus by Intact IgG and Fab Fragments. Williams JA, Gui L, Hom N, Mileant A, Lee KK. J Virol. 2018 Feb 26;92(6). pii: e02006-17. doi: 10.1128/JVI.02006-17. Print 2018 Mar 15.
- Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. Torrents de la Peña A, Julien JP, de Taeye SW, Garces F, Guttman M, Ozorowski G, Pritchard LK, Behrens AJ, Go EP, Burger JA, Schermer EE, Sliepen K, Ketas TJ, Pugach P, Yasmeen A, Cottrell CA, Torres JL, Vavourakis CD, van Gils MJ, LaBranche C, Montefiori DC, Desaire H, Crispin M, Klasse PJ, Lee KK, Moore JP, Ward AB, Wilson IA, Sanders RW. Cell Rep. 2017 Aug 22;20(8):1805-1817. doi: 10.1016/j.celrep.2017.07.077.
- Extracellular Matrix Proteins Mediate HIV-1 gp120 Interactions with α4β7. Plotnik D, Guo W, Cleveland B, von Haller P, Eng JK, Guttman M, Lee KK, Arthos J, Hu SL. J Virol. 2017 Oct 13;91(21). pii: e01005-17. doi: 10.1128/JVI.01005-17. Print 2017 Nov 1.
Herb’s time at the School of Pharmacy lead him to a life rich in love, charity and service. During his 50-year career as a pharmacy owner and clinical pharmacist, he always found a way to support his communities. From founding the Walk for Rice, a fundraising walk to support the Asian Counseling and Referral Service food bank, to donating his expertise to the Rainier Vista Clinic Pharmacy where he sourced low-cost drugs for in-need communities, Herbert was always dedicated to his community. Herbert received the Pharmacy Alumni Association Distinguished Alumni Award in 2008, in addition to the A.H. Robins/Wyeth Bowl of Hygeia Award and a Seattle Mayor’s Small Business Award for excellence in management, entrepreneurial spirit and customer service. He is a member of the National Community Pharmacists Association and Washington State Pharmacy Association, and a former longstanding member of the American Pharmaceutical Association and Seattle-King County Pharmaceutical Society.
Ph.D. Medicinal Chemistry, 1998 
PharmD, 2003
PharmD, 2003
Ph.D. Pharmaceutical Sciences (CHOICE), 2001
PharmD, 2003
PharmD, 2005
B.S. Pharmacy, 1989
B.S. Pharmacy, 1970
PharmD, 1990 
B.S. Pharmacy, 1997
Born in Nebraska in 1892, Louis D. (L.D.) Bracken attended the UW School of Pharmacy from 1912-1913. He went on to found the L.D. Bracken Pharmacy in 1921, ultimately with locations in downtown Seattle in the Cobb Building and on First Hill. In the great tradition of compounding pharmacists, L.D. was an inventor, in addition to being an entrepreneur and health care provider. 
Henry Hank Ichiro Yamamura, ’64, died peacefully at home in September 2008 in Tucson, Ariz, at age 68. After earning his B.S. in pharmacy, he got his Ph.D. in pharmacology from the UW School of Medicine in 1969. He joined the University of Arizona in 1975 as associate professor in the Department of Pharmacology. He joined the College of Medicine in 1990 and took the position of Regent’s Professor of Pharmacology in 1997. Yamamura was internationally known for his scholarly research. He was the School of Pharmacy’s distinguished alumnus for excellence in pharmaceutical sciences in 2004.
Don attended the University of Washington nearly 72 years ago and took classes on the 3rd floor of Bagley Hall. When asked why he chose pharmacy, he said that he had been working at JCPenney’s in Ritzville, WA and really enjoyed customer service, but also had a love for chemistry. He thought that pharmacy would be a great way to do both. 
Jim L. Bracken, followed in his father’s footsteps, graduating from UWSOP in 1945 and then joining his father’s pharmacy business. When L.D. died in 1954, Jim became president of the company. L.D. and Jim were beloved leaders in the profession, serving as presidents of the Washington State Pharmacists Association and as founding members of the American College of Apothecaries.
Alice was born in Seattle in 1892. After graduating from Seattle High School, she became one of the first African-American women to study at the UW School of Pharmacy in 1910. She graduated in 1914 with a degree in pharmaceutical chemistry and a B.S. in pharmacy. After the UW, she moved to Hawaii to earn her master’s degree and teach at the University. 
Bill received his Ph.D. in medicinal chemistry — focusing on conformational analysis and nuclear magnetic resonance — from the University of Washington in 1965 under the supervision of the recently deceased Professor Alain Huitric. Bill went on to do his postdoctoral studies at the Chelsea School of Science and Technology in London, studying alkaloid structures with Sir Arnold Beckett. 
Ed Wong was formerly Vice President of Pharmacy and Clinical Programs at Premera Blue Cross. He was responsible for pharmacy programs, care management, disease management and vendor contracting. While at the Blue Cross Blue Shield Association, he was a member of the National Council of Physician and Pharmacist Executives, served as Chair of the Pharmacist Work Group and received the Best of Blues Award. He received the 2005 Premera CEO Award for outstanding leadership.
After earning his PharmD, Brian worked for independent community pharmacies before joining the Kelley-Ross Pharmacy Group, where he helped move Kelley-Ross from a mixed-model to a closed-door, long-term care pharmacy. Brian is currently the Chief Financial Officer and manages the Union Center Pharmacy for the Kelley-Ross Pharmacy Group. Brian was presented with the 2015 National Community Pharmacists Association Prescription Drug Safety Award for his work to expand access to the overdose antidote naloxone and continues to fight the opioid overdose crisis by working to reduce the stigma surrounding opioid overdoses.
Susan is currently Senior Consultant with ASHP Consulting Services and serves as primary faculty member for the ASHP Pharmacy Leadership Academy. 
Larry C. Wienkers received his BS in Chemistry and Biology in 1986 and his MS in Chemistry in 1988 from Western Washington University. He then earned his Ph.D. in Medicinal Chemistry from University of Washington in 1993 under the direction of Dr William F. Trager. He did postdoctoral work in the department of Drug Metabolism at the Upjohn Company and subsequently joined the company as a Research Scientist 1995. 
Gayle Hudgins, Pharm. D., BCGP, is a Professor Emerita of the University of Montana Skaggs School of Pharmacy in the Department of Pharmacy Practice. She is a 1969 graduate of the University of Washington School of Pharmacy with a B.S. degree in Pharmacy and a 1976 graduate of Duquesne University with a Doctor of Pharmacy degree. She also completed a pharmacy practice residency at Mercy Hospital in Pittsburgh. 
Growing up the son of a pharmacist in Tacoma, Richard spent his high school years working at the family store, Nelson Drug Company, before pursuing his own Pharmacy degree at the University of Washington in 1962. 
Al holds degrees from Central Washington State BS in Zoology, University of Washington BS Pharmacy, Class of 1971, and an MBA Fuqua School of Business at Duke University. 
Duane D. Miller, born 1943, grew up on a farm in Larned Kansas. He obtained his B.S. degree in Pharmacy at Kansas University in 1966, and his interest in research was stimulated by two professors at the University of Kansas, Dr. Ed Smissman and Dr. Matt Mertes. As a National Science Foundation Undergraduate Research Fellow, he worked on anticancer drugs. He next moved to Seattle, Washington and was an NIH Fellow while at the University of Washington and obtained his Ph.D. in Medicinal Chemistry in 1969, under the mentorship of Dr. Wendel L. Nelson and did research on conformationally restricted analogs of ephedrine. He next joined The Ohio State University Faculty in 1969, where he became Professor and Chairman of the Division of Medicinal Chemistry and Pharmacognosy in 1982. He studied dopamine and norepinephrine analogs with Drs. Popat Patil, Norman Uretsky and Dennis Feller. He moved to the University of Tennessee Health Science Center in Memphis, TN in 1992, as the Van Vleet Endowed Professor of The Department of Pharmaceutical Sciences in the College of Pharmacy. He was made chair of the Department of Pharmaceutical Sciences in 2001. 
Dr. Nanci Murphy’s past roles at the University of Washington include, Collaborative Practice Specialist, Co-Director of the Center for Health Sciences Interprofessional Education, Research and Practice, and Associate Dean and Director of Student Leadership Programs for the School of Pharmacy. She received her PharmD degree from UW SOP in 1997. She looks forward to the next chapter of her post-retirement career contributing to an international work force group focused on interprofessional education and collaborative practice.
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.
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.
Shirley is a Seattleite, born and raised. From a young age, she dedicated her life to advocating for women, children, human rights and healthcare. Encouragement from her mother, and her knack for science, led Shirley 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. Brady was recruited to join the University of Washington by Tip Tyler, a School of Pharmacy Faculty member studying mushrooms and ergot. After completing his Ph.D. at the School of Pharmacy, Lynn joined the faculty and eventually became the first chair of the then-named Department of Pharmaceutical Sciences. As a graduate student, Lynn authored or co-authored over 100 research and review articles and later in his career authored the major textbook in the field of Pharmacognosy. Lynn was very passionate about the Medicinal Herb Garden and was on the steering committee for the Friends of the Medicinal Herb Garden.
George Benson, also known as the Father of the Waterfront Street Trolley, was a WWII Navy Veteran, five-term City Council member, owner of Mission Street Pharmacy and one of the founders of the Friends of the Medicinal Herb Garden. George was nothing short of a passionate person, known throughout his life for his caring nature. He was devoted to his wife Evelyn, who was a fellow Pharmacy alumna, their business and spearheading the development of the Waterfront Streetcar.
Dr. Plein and her late husband Elmer, are widely credited for creating the momentum for senior-care pharmacy in the state of Washington at a time when few pharmacists were geriatricians and had few resources to advocate for older patients. In 1973, they developed a nursing home pharmacy course at the School of Pharmacy and Foss Home, a nursing home, with the help of a graduate student. Throughout her career, she was honored with several awards and is a beloved member of the School of Pharmacy.
Phil received a pharmacy degree from the University of Washington in 1964 and by 1975, was the Head of Pharmacy for Group Health. That same year he unveiled the Co-OPRx computerized prescription system that provided doctors and pharmacists instant access to patient drug histories, potential allergies and adverse reactions. The Co-CORx project sparked his interest in innovation, which became the cornerstone of his career. He went on to help Group Health expand into Bellevue and rose to a top leadership position with Group Health and Kaiser Operations in the Northwest.
Virginia graduated from the School of Pharmacy in 1943 and while in school, she was a member of the Totem Club and Chi Omega Sorority. Virginia was one of the first women pharmacists to work in a hospital setting, which was remarkable in the 1940s. During her career, she conducted research on motion sickness medication for soldiers in World War II, studied breast cancer at the University of Rochester Medical School and was the first pharmacist at the Monadnock Hospital. She spent 17 years as a relief pharmacist and traveled the world after opening her travel company.
George H. Bartell Jr. started his career in the family business stocking shelves and went on to grow Bartell Drugs into the oldest family-owned drugstore chain in the nation. After becoming the President of Bartell Drugs in 1939, George served in World War II and came back to a world changed. Among these changes were new Pharmacist licensing laws in Washington State that required George to become licensed. After joining the School of Pharmacy, he earned his Pharmacy Degree (and became licensed) in just three years. George was an avid Husky Football fan and a supporter of local organizations such as the Rainier Club, Seattle Golf and Country Club, the Scottish Rite Temple and the Seattle Chamber of Commerce.
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.
Jonathan Watanabe, ‘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.