Lin Chen

BIOGRAPHY

EDUCATION:

Ph.D. Harvard University 1994

B.S. Peking University 1986

MEMBERSHIPS/AWARDS:

1999 Damon Runyon Scholar Award

1997 Fellow of the Charles A. King Trust Medical Foundation

1994 Fellow of the Cancer Research Fund of the Damon Runyon-Walter Winchell Foundation

RESEARCH INTERESTS: We are interested in the structure and function of molecular complexes that control signal transduction and gene expression inside cells. A major area of our research has been to elucidate the structure of multi-component transcription factor complexes in order to understand the combinatorial mechanism of eukaryotic transcription. This mechanism was initially proposed more than a decade ago to explain the synergy of different transcription factors. Now in the post genomic era, bio-informatic studies suggest that eukaryotic genes are regulated by multiple highly conserved regulatory motifs in the promoter region (called the cis-regulatory code), reinforcing the concept of combinatorial control. We have been carrying out systematic structural and biochemical studies of a number of transcription factors from the immune, muscle and nervous systems, including NFAT, MEE2, FOXP, and GATA (Chen et al, Nature, 1998; Han et al, Nature, 2003, Wu et al, Cell, 2006). Our studies have demonstrated that protein-protein interaction between distinct transcription factors on specifically arranged binding sites is at least one fundamental principle of the combinatorial mechanism of eukaryotic transcription. An exciting new direction of the lab is to use a variety of biophysical methods such as fluorescence resonance energy transfer (FRET), small angle X-ray scattering (SAXS), Electron Microscopy (EM) and X-ray crystallography to study the structure and assembly mechanisms of full length transcription factors and their interactions with co-activators/Mediators. Our ultimate goal is to understand, in the context of natural promoter and chromatin structure, how cis-regulatory codes of eukaryotic genomes are decoded by transcription factor complexes.Building on our experience in structural studies of higher-order protein complexes and the strength of USC Neuroscience program, we have recently initiated a new research project of neuro-structural biology. We use X-ray crystallography, EM and other biophysical and biochemical methods to study the structure and function of molecular complexes involved in signal sensing and communication in the nervous system. We have recently made a major breakthrough in our structural study of the nicotinic acetylcholine receptor in collaboration with Professor Zuo-Zhong Wang of the Zilkha Neurogenetic Institute. Another important aspect of our research is to combine structural biology and chemical design to study the function of bio-macromolecular complexes. We will attempt to develop cell permeable small molecule inhibitors of specific protein complexes to further address their functions in vivo. These studies have the potential to develop drugs for treating human diseases.