Trainee Spotlight: Yu-Chung (Eric) Chang, PhD
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Yu-Chung (Eric) Chang, PhD
Postdoctoral Associate
Dr. Jinhua Wu’s Lab
Fox Chase Cancer Center
[email protected]Biography
Since I was young, I have always wondered how things function inside a cell. My interest in protein interaction and enzyme mechanism led me to pursue a degree in biochemistry and molecular biology at University of California, Irvine. To advance my understanding in protein functions at the molecular level, I joined Cynthia Stauffacher’s lab at Purdue University to learn about X-ray crystallography and perform structural and enzymological studies of Enterococcus faecalis 3-hydroxy-3-methylglutaryl coenzyme A synthase. For my postdoctoral training, I joined Jinhua Wu’s lab at Fox Chase to study the interaction and recruitment mechanism of talin by RIAM in integrin activation pathway using a combination of X-ray crystallography, biochemical assays, and in-cell functional studies. My career goal is to focus on the development of structural based drug designs in cancer therapeutics.
Research Overview
Integrins are heterodimeric transmembrane receptors that mediate cell proliferation, adhesion and migration. These receptors also promote an inflammatory response and tumor progression. An integrin signaling cascade can be activated through a talin-dependent pathway that is initiated by the recruitment of RIAM via membrane bound GTPase Rap1. RIAM in turn recruits talin to the plasma membrane. Therefore, talin may serve as an important drug target in cancer therapeutic developments. In this published work, we described the role of the two talin binding sites (TBS1 and TBS2) of RIAM in talin recruitment and why a close homolog of RIAM, lamellipodin, failed to recruit talin. We performed both X-ray crystallographic and cell-based functional studies. The crystal structure of TBS1 and R7R8 complex reveals both hydrophobic and electrostatic interactions, and a unique kinked helical conformation in TBS1, which is absent in lamellipodin. Mutations of contact residues and disruption of the kinked conformation abolish talin recruitment and integrin activation. Our study also demonstrates that the TBS1 region, but not the TBS2 region, interacts with cytoplasmic talin and the R8 domain of talin is the strongest binding site for TBS1 region. Thus, this work provides the structural and mechanistic insights into talin recruitment by RIAM in integrin signaling.
Featured Publication
Chang YC, Zhang H, Brennan ML, Franco-Barraza J, Patel T, Cukierman E, Wu J. Structural and mechanistic insights into the recruitment of talin by RIAM in integrin signaling. Structure 2014 22(12):1810-20 ScienceDirect
The Scientist Rates Fox Chase a Best Place to Work in Academia
The Scientist rates Fox Chase Cancer Center 7th on the list of Top Ten Best Places to Work Academia 2013.