Dr. Hui Sun's research is focused on the discovery and mechanistic study of new therapeutic targets to treat cancer. His lab discovered a long-sought receptor that takes up vitamin A from the blood. This receptor turned out to be a protein originally known as a cancer cell-surface marker that is expressed more than 100 times higher in cancer tissues than normal tissues. His team also discovered a technique of using small molecules to potently stimulate retinoid influx through this receptor, and some of these molecules are known to have anti-cancer activities. Sun is currently investigating mechanistic studies that suggest that some cancer-inhibiting chemicals may inhibit growth through the receptor-mediated influx of retinoid, which can then further inhibit cell growth.
In addition, Sun's lab is studying a secreted factor, PEDF, with a broad therapeutic value in treating diverse diseases through its antiangiogenic, antitumorigenic and antimetastatic activities. Numerous animal models have demonstrated its ability to inhibit a wide range of cancer types including prostate and pancreatic cancers, melanoma, neuroblastoma, osteosarcoma, hepatoblastoma, Lewis lung carcinoma, chondrosarcoma, gastric carcinoma, glioma and Wilm's tumor. However, how PEDF acts on its target cells had long been a scientific puzzle until, after many years of arduous effort, Sun and his team identified two cell-surface transmembrane receptors for PEDF. They showed that PEDF activates these receptors through a new mechanism. Continued investigation of the long-sought PEDF receptors will make it possible to study its fundamental molecular mechanisms and to develop more specific and potent therapeutics.
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 Dec 23;3:e05401. doi: 10.7554/eLife.05401.
Kawaguchi R, Zhong M, Kassai M, Ter-Stepanian M, Sun H. Differential and isomer-specific modulation of vitamin A transport and the catalytic activities of the RBP receptor by retinoids. J Membr Biol. 2013 Aug;246(8):647-60. doi: 10.1007/s00232-013-9578-z. Epub 2013 Jun 29.
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. 2007 Feb 9;315(5813):820-5. Epub 2007 Jan 25.