2018 Scientific Report
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Center for Cancer and Cell Biology<br />
H. ERIC XU, Ph.D.<br />
Dr. Xu went to Duke University and the University of Texas Southwestern<br />
Medical Center, earning his Ph.D. in molecular biology and biochemistry.<br />
He joined VARI in July 2002 and is now a Professor. Dr. Xu is also the<br />
Primary Investigator and Distinguished Director of the VARI–SIMM<br />
Research Center in Shanghai, China.<br />
RESEARCH INTERESTS<br />
Hormone signaling is essential to eukaryotic life. Our research focuses on the<br />
signaling mechanisms of physiologically important hormones, striving to answer<br />
fundamental questions that have a broad impact on human health and disease.<br />
We are studying two families of proteins, the nuclear hormone receptors and the<br />
G protein–coupled receptors (GPCRs), because these receptors are fundamentally<br />
important for treating major human diseases.<br />
STAFF<br />
Xiang Gao, Ph.D.<br />
Yanyong Kang, Ph.D.<br />
Michelle Martin, A.A.<br />
Kelly Powell, B.S.<br />
Xiaoyin (Edward) Zhou, Ph.D.<br />
STUDENTS<br />
Parker de Waal, B.S.<br />
Yan Yan, B.S.<br />
VISITING SCIENTIST<br />
Ross Reynolds, Ph.D.<br />
Nuclear hormone receptors<br />
The nuclear hormone receptors form a large family comprising ligand-regulated<br />
and DNA-binding transcription factors, which include receptors for the classic<br />
steroid hormones such as estrogen, androgens, and glucocorticoids, as well as<br />
receptors for peroxisome proliferator activators, vitamin D, vitamin A, and thyroid<br />
hormones. These receptors are among the most successful targets in the history<br />
of drug discovery: every receptor has one or more synthetic ligands being used<br />
as medicines. In the last five years, we have developed projects centering on<br />
the peroxisome proliferator–activated receptors (PPARα, β, and γ), the human<br />
glucocorticoid receptor, the androgen receptor, and a number of orphan nuclear<br />
receptors including CAR, SHP, SF-1, COUP-TFII, and LRH-1. We have solved many of<br />
their structures and identified small-molecule ligands for several of them, including<br />
potent ligands for GR, AR, PPARs, and COUP-TFII, which could be developed into<br />
therapeutics against diabetes, cancer, and inflammatory disease.<br />
G protein–coupled receptors<br />
The GPCRs form the largest family of cell-surface receptors (over 800 members)<br />
and account for over 40% of drug targets. There are only a few dozen solved GPCR<br />
structures because they are seven-transmembrane receptors. Many important<br />
questions regarding GPCR ligand binding and activation remain unanswered,<br />
including pressing questions about the assembly of GPCR signaling complexes that<br />
have downstream effects, such as G protein, arrestin, and GPCR kinases. Our group<br />
aims to use rhodopsin, the prototypical GPCR, as a model system for understanding<br />
how an activated GPCR is assembled with the GPCR downstream signaling effectors.<br />
Answering these basic questions could help in the design of pathway-selective GPCR<br />
ligands as drugs.<br />
16 | VAN ANDEL RESEARCH INSTITUTE SCIENTIFIC REPORT