Yan Chen, PhD
Assistant Professor, UTMB Department of Ophthalmology & Visual Sciences
Dr. Chen received her Ph.D. from Emory University under the mentorship of Dr. Dean Jones, an internationally renowned toxicologist who has made major contributions to the field of oxidative stress and redox regulation. After graduation, she joined the Vanderbilt Eye Institute as a postdoctoral fellow where she studied molecular mechanisms underlying age-related macular degeneration (AMD). She was one of the four recipients of K99/R00 Pathway to Independence Award from National Eye Institute in 2010. She joined the University of Texas Medical Branch in 2012.
Dr. Chen's current research efforts are directed toward characterizing the functional roles of mammalian target of rapamycin (mTOR)-mediated signaling in aging of the retinal pigment epithelium (RPE) and AMD. The long-term goal of her research is to explore novel therapeutic options for treating AMD, the leading cause of blindness among elderly people.
mTOR is an evolutionary conserved large serine/threonine protein kinase, which integrates upstream signals from nutrients, growth factors and energy level and controls cell growth and proliferation. In mammals, there are two signaling complexes of mTOR (mTORC1 and mTORC2), and they carry out distinct functions. A growing body of evidence supported the central roles of mTOR-mediated signaling in controlling aging and age-related neuro-degenerative diseases. Whether mTOR regulates tissue-specific degeneration of the retina remains elusive.
RPE plays key roles in maintaining and supporting structure and functions of the retina. Our previous studies show that responses of mTORC1 are up-regulated in the aged RPE cells. Down-regulation of mTORC1 signaling by the pharmacological inhibitor rapamycin delayed the appearance of senesce-associated phenotypical changes. Based on these findings, we hypothesize that mTOR-related signaling network will likely contribute to degeneration of the RPE. Currently, our lab is working on exploring the age-associated spatial and temporal changes of mTOR signaling in the RPE using in vivo models. Another project in Dr. Chen's lab is to investigate the roles of endogenous inhibitor FKBP8 in the aging of the RPE.
FK506-binding proteins (FKBPs) are a major family of immunophilins that bind to immunosuppressive drugs, FKB506 and rapamycin. FKBP8 (also known as FKBP38) localizes in mitochondria as well as ER and regulates apoptosis. We previously showed that in the human RPE cells, FKBP8 gene is expressed along with a splicing variant FKBP8s lacking the FKBP domain. Both of those proteins showed inhibitory effects on mTORC1 signaling. The roles of those proteins in the regulation of RPE functions are under investigation.