Professor, Physiology, University of California Los Angeles
Professor, Ophthalmology, University of California Los Angeles
Member, Biochemistry, Biophysics & Structural Biology GPB Home Area, Brain Research Institute, Molecular, Cellular & Integrative Physiology GPB Home Area
Receptors are among the most successful therapeutic targets in medicine. We are interested in the discovery and mechanistic study of new membrane receptors that play critical roles in physiology and diseases and to target these receptors to develop novel small molecule-based therapeutics. In 2007, we solved a three decades-old scientific problem by identifying a new type of receptor using a new technical strategy. This multitransmembrane receptor mediates cellular uptake of vitamin A, a chemical compound that has diverse biological functions in different organs and is essential for human vision and human survival. Using sensitive real-time monitoring techniques that we developed, we revealed that the transmembrane transport mechanism of this receptor/transporter is unlike any known receptor or transporter and further identified small molecules the potently modulate its activity. Another long-standing scientific problem that we tackled was to identify the transmembrane receptor for the most potent endogenous antiangiogenic factor that is known to suppress the pathogenesis of several major diseases. This was previously an insurmountable hurdle that prevented the development of small molecule-based medicines directed at this natural therapeutic pathway. We recently identified the receptors for this factor as a new type of transmembrane receptors with a new signaling mechanism. We further developed an innovative cell-based technique to identify chemical compounds that specifically target these receptors, and we identified the first chemical compounds that mimic the factor’s function in vitro and in vivo. These novel chemical compounds are potential first-in-class drugs to treat devastating blinding diseases and cancer.
Dr. Sun is Professor of Physiology and Ophthalmology in the Department of Physiology and Stein Eye Institute, David Geffen School of Medicine at UCLA. He is also a member of the Jonsson Comprehensive Cancer Center. He received his Ph.D. from Johns Hopkins University in 1998. He came to UCLA in 2003 as an Assistant Professor and received the prestigious Early Career Scientist Award from the Howard Hughes Medical Institute in 2009. He has taught in a variety of courses related to physiology and human diseases at UCLA Medical School, UCLA Dental School and UCLA Graduate School.
A selected list of publications:
- Kawaguchi, R., Yu, J., Honda, J., Hu, J., Whitelegge, J., Ping, P., Wiita, P., Bok, D., and Sun, H. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A, Science, 2007; 315: 820-825.
- Yang, Z., Camp, N., Sun, H., Tong, Z., Gibbs, D., Cameron, J., Chen, H., Zhao, Y., Pearson, E., Li, X., Chien, J., DeWan, A., Harmon, J., Bernstein, P., Shridhar, V., Zabriskie, N., Hoh, J., Howes, K., and Zhang, K. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration, Science, 2006; 314: 992-993.
- Jin, M., Li, S., Moghrabi, W.N., Sun, H., and Travis, G.H. RPE65 is the retinoid isomerase in bovine retinal pigment epithelium, Cell, 2005; 122: 449-459.
- Sun, H., and Kawaguchi, R. The Membrane Receptor for Plasma Retinol Binding Protein, a New Type of Cell-Surface Receptor, Int Rev Cell Mol Biol. , 2011; 288(1-41): .
- Kawaguchi, R., Yu, J., Ter-Stepanian, M., Zhong, M., Guo, C., Yuan, Q., Jin, M., Travis, G.H., Ong, D., and Sun, H. Receptor-Mediated Cellular Uptake Mechanism that is Coupled to Intracellular Storage, ACS Chemical Biology , 2011; 6: 1041-51.
- Cheng, G., Zhong, M., Kawaguchi, R., Kassai, M., Al-Ubaidi, M., Deng, J., Ter-Stepanian, M., and Sun, H. Identification of PLXDC1 and PLXDC2 as the Transmembrane Receptors for the Multifunctional Factor PEDF. , eLIFE, 2014; 3: e05401.
- Zhong, M., and Sun, H. A Genetic Clog in the Vitamin A Transport Machinery, Cell, 2015; 161 (3): 435-437.
Awards and Honors
- E. Matilda Ziegler Foundation Award, E. Matilda Ziegler Foundation, 2005-2008.
- Alicia Showalter Reynolds Research Prize, Johns Hopkins University, 1998.
- Ellison Medical Foundation New Scholar Award, Ellison Medical Foundation, 2006-2010.
- Gerald Oppenheimer Family Foundation Award, UCLA, 2005.
- Howard Hughes Medical Institute Early Career Scientist Award, Howard Hughes Medical Institute, 2009-2015.
- Karl Kirchgessner Foundation Award, Karl Kirchgessner Foundation, 2003.
- Ruth and Milton Steinbach Award, Ruth and Milton Steinbach Foundation, 2004-2007.
- Stein-Oppenheimer Endowment Award, UCLA, 2004.
- Zhong M, Kawaguchi R, Costabile B, Tang Y, Hu J, Cheng G, Kassai M, Ribalet B, Mancia F, Bok D, Sun H. Regulatory mechanism for the transmembrane receptor that mediates bidirectional vitamin A transport.. Proceedings of the National Academy of Sciences of the United States of America, 2020.
- Cook JD, Ng SY, Lloyd M, Eddington S, Sun H, Nathans J, Bok D, Radu RA, Travis GH. Peropsin modulates transit of vitamin A from retina to retinal pigment epithelium.. The Journal of biological chemistry, 2017.
- Kawaguchi R, Zhong M, Kassai M, Ter-Stepanian M, Sun H. Vitamin A Transport Mechanism of the Multitransmembrane Cell-Surface Receptor STRA6.. Membranes, 2015.
- Zhong M, Sun H. A genetic clog in the vitamin A transport machinery.. Cell, 2015.
- Cheng G, Zhong M, Kawaguchi R, Kassai M, Al-Ubaidi M, Deng J, Ter-Stepanian M, Sun H. Identification of PLXDC1 and PLXDC2 as the transmembrane receptors for the multifunctional factor PEDF.. eLife, 2014.
- Kawaguchi R, Zhong M, Sun H. Real-time analyses of retinol transport by the membrane receptor of plasma retinol binding protein.. Journal of visualized experiments : JoVE, 2013.
- Kawaguchi R, Zhong M, Kassai M, Ter-Stepanian M, Sun H. STRA6-catalyzed vitamin A influx, efflux, and exchange.. The Journal of membrane biology, 2012.
- Kawaguchi R, Yu J, Ter-Stepanian M, Zhong M, Cheng G, Yuan Q, Jin M, Travis GH, Ong D, Sun H. Receptor-mediated cellular uptake mechanism that couples to intracellular storage.. ACS chemical biology, 2011.
- Kawaguchi R, Sun H. Techniques to study specific cell-surface receptor-mediated cellular vitamin A uptake.. Methods in molecular biology (Clifton, N.J.), 2010.
- Kawaguchi R, Yu J, Wiita P, Honda J, Sun H. An essential ligand-binding domain in the membrane receptor for retinol-binding protein revealed by large-scale mutagenesis and a human polymorphism.. The Journal of biological chemistry, 2008.
- Yu J, Wiita P, Kawaguchi R, Honda J, Jorgensen A, Zhang K, Fischetti VA, Sun H. Biochemical analysis of a common human polymorphism associated with age-related macular degeneration.. Biochemistry, 2007.
- Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A.. Science (New York, N.Y.), 2007.
- Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, Howes K, Zhang K. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration.. Science (New York, N.Y.), 2006.
- Jin M, Li S, Moghrabi WN, Sun H, Travis GH. Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium.. Cell, 2005.
- Tsunenari T, Sun H, Williams J, Cahill H, Smallwood P, Yau KW, Nathans J. Structure-function analysis of the bestrophin family of anion channels.. The Journal of biological chemistry, 2003.
- Sun H, Tsunenari T, Yau KW, Nathans J. The vitelliform macular dystrophy protein defines a new family of chloride channels.. Proceedings of the National Academy of Sciences of the United States of America, 2002.
- Sun H, Nathans J. The challenge of macular degeneration.. Scientific American, 2001.
- Sun H, Smallwood PM, Nathans J. Biochemical defects in ABCR protein variants associated with human retinopathies.. Nature genetics, 2000.
- Sun H, Molday RS, Nathans J. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease.. The Journal of biological chemistry, 1999.
- Chen S, Wang QL, Nie Z, Sun H, Lennon G, Copeland NG, Gilbert DJ, Jenkins NA, Zack DJ. Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes.. Neuron, 1997.
- Sun H, Macke JP, Nathans J. Mechanisms of spectral tuning in the mouse green cone pigment.. Proceedings of the National Academy of Sciences of the United States of America, 1997.
- Allikmets R, Singh N, Sun H, Shroyer NF, Hutchinson A, Chidambaram A, Gerrard B, Baird L, Stauffer D, Peiffer A, Rattner A, Smallwood P, Li Y, Anderson KL, Lewis RA, Nathans J, Leppert M, Dean M, Lupski JR. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy.. Nature genetics, 1997.