2018 Scientific Report

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