Lin Chen

Tenure Track Appointments

• Professor, University of Southern California, 2022-2023

Summary Statement of Research Interests

The research focus of our lab is to understand the mechanisms of transcription regulation and signal transduction at the molecular level. The lab uses a multidisciplinary approach, combining structural, biophysical, biochemical/chemical biology, and genomics methods to explore cellular mechanisms at the molecular and systems levels. One of the lab’s past research projects involved studying the structure of transcription factor complexes and signaling complexes, such as the NFAT/Fos-Jun/DNA complex, the NFAT/FOXP3/DNA c0omplex, and the nicotinic acetylcholine receptor complex. Through these studies, the lab observed frequent DNA bridging by certain transcription factors, leading to a new research project on mapping long-range chromatin interactions in cells to study their roles in gene regulation.
The lab has also been developing new molecular tools to enable novel exploration of biological mechanisms and disease origins. Another current project in the lab involves exploring the potential of RNA mutation in protein folding, inspired by the work of our colleague Professor Marc Vermulst of Gerontology who has been sequencing RNA in a number of cells. The lab has noticed that a subtle mutation in MEF2 could induce a dramatic switch of an alpha helix into a beta strand that initiates the formation of extended beta sheet-like those seen in beta amyloid. The lab’s new project is to test the hypothesis that some RNA mutations could cause amino acid changes in certain proteins that cause amyloid and prion formation, which could be a mechanism by which rare RNA errors could lead to functional changes in aging-related diseases, especially neurodegenerative diseases.

Research Keywords

Structural Biology, Chemical Biology, Computational Biology, Mechanisms of eukaryotic gene regulation: higher-order transcription factor/DNA complexes and long-range chromatin interactions, structure and function of the genome; small molecule-based transcription and epigenetic modulators; Structure and function of nicotinic acetylcholine receptors (nAChR) and ligand-gated ion channels (LGICs); Structure-guided development of anti-viral drugs; RNA mutation and damage induced protein misfolding and amyloid/prion formation.

Detailed Statement of Research Interests

 We seek to understand the mechanisms of transcription regulation and signal transduction at the molecular level. The early part of our studies has been largely centered on structural analyses of transcription factor complexes (e.g., the NFAT/Fos-Jun/DNA complex, Nature, 392, 42,1998 and the NFAT/FOXP3/DNA complex, Cell, 126, 375, 2006) or the signaling complex (e.g., the nicotinic acetylcholine receptor complex – nAChR, Nature Neuroscience, 10, 953, 2007).  From the studies of transcription factor/DNA complexes, we noticed frequent DNA bridging by certain transcription factors such as FOXP3 (Immunity, 34, 479, 2011) and GATA3 (Cell Reports, 2, 1197, 2012).  Intrigued by these observations, we started a new research project to map long range chromatin interactions in cells in order to study their roles in gene regulation (Nature Biotechnology, 30, 90, 2012, awarded US Patent 8076070). These past studies have led to our current effort to explore cellular mechanism at the molecular and systems levels using a multidisciplinary approach.  We combine structural, biophysical, biochemical/chemical biology and genomics methods. We have also been actively developing new molecular tools that enable the expansion and deepening of our perception of biological mechanisms and disease origins.  

Another project in the lab is to explore the potential of RNA mutation in protein folding.  This study is inspired by the work of Marc Vermulst who has been sequencing RNA in a number of cells.  Based on a recent work in my lab (Lei et al., JMB, 430, 1157, 2018), we have noticed that a subtle mutation in MEF2 could induce a dramatic switch of an alpha helix into beta strand that initiate the formation of extended beta sheet like those see in beta amyloid. The new project is to test the hypothesis if some of the RNA mutations could cause amino acid changes in certain proteins that cause amyloid and prion formation.  If true, this could be a mechanism by which rare RNA errors could lead to functional changes, especially in a wide range of aging-related diseases such as the neurodegenerative diseases. 

For more information, check our publications at Google scholar:

https://scholar.google.com/citations?user=LGp68QwAAAAJ&hl=en

Contracts and Grants Awarded

• Bi-functional photo-crosslinking (BFPX) for genome-wide study of protein-nucleic acid interactions, (NIH/NHGRI), Lin Chen, $453,750, 11/28/2022 – 04/30/2025
• Image-directed nanoscale photo-crosslinking for the study of sub-nuclear structures, (NIH/NHGRI), Lin Chen, $453,750, 09/06/2019 – 08/31/2022
• Mapping the 3D Genome Landscape, (NIH/NIDDK), Lin Chen, Frank Alber, $12,422,723, 09/30/2015 – 07/31/2022
• Explore FOXP3’s role in the 3D organization of the genome, (NIH/NIAID), Lin Chen, $329,000, 08/01/2014 – 12/31/2020
• Structural and functional versatility of NFAT, (NIH/NIGMS), Lin Chen, $1,228,000, 02/01/2005 – 05/31/2017

• (Spring 2020) BISC 502B. Molecular Genetics and Biochemistry, MW 02:00pm – 04:00pm, RRI301
• (Spring 2022) BISC 502B. Molecular Genetics and Biochemistry, MW 02:00pm – 04:00pm, RRI301
• (Spring 2022) CHEM 432. Physical Chemistry for the Life Sciences, MWF 10:00am – 10:50am, KAP158
• (Spring 2023) BISC 502B. Molecular Genetics and Biochemistry, MW 02:00pm – 04:00pm, RRI301

• BISC 461 (Section 13464D): Biotechnology and Chemical Biology in Modern Biomedical Research, BISC, 2022-2023