Chong-Shan Shi, M.D., Ph.D.

B-Cell Molecular Immunology Section

NIH Main Campus, Bethesda, MD

Chong-Shan Shi, M.D., Ph.D.

Staff Scientist

Major Areas of Research

  • Inflammation and autophagy mechanisms
  • Investigating mechanisms explaining how SARS-CoV-1 and SARS-CoV-2 proteins manipulate host cell function to promote virus growth
  • Signaling transduction for innate immunity

Program Description

Molecular biology and biochemistry techniques are used for investigating signaling transduction mechanisms in macrophages. Our research program focuses on SARS-CoV-1 and SARS-CoV-2, exploring proteins that manipulate the host cell’s immune response and cause multiple host cell organelle stress and cell death. Through our research, we find a potential host cell anti-virus protein, which leads to a new therapy target.

We also participate in a clinical trial program. We explore effective therapeutic strategies for retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis and headache (ROSAH) syndrome through our research on pathogenesis on genetic gain-function mutants of ALPK1 kinase.

Biography

Education

M.D., 1982, Huaxi Xiehe College in China. Ph.D., 1990 The Fourth Military University in China

Dr. Shi obtained his M.D. from Huaxi Xiehe College in China in 1982, and completed his Ph.D. at The Fourth Military University in China in 1990. Next, he conducted postdoctoral research in Dr. John H. Kehrl’s B-Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, in 1995. In 2000, he became a research fellow and has been a staff scientist in the B-Cell Molecular Immunology Section since 2002.

Selected Publications

Hwang IY, Kim JS, Harrison KA, Park C, Shi CS, Kehrl JH. Chemokine-mediated F-actin dynamics, polarity, and migration in B lymphocytes depend on WNK1 signaling. Sci Signal. 2024 Aug 27;17(851):eade1119.

Nabar NR, Heijjer CN, Shi CS, Hwang IY, Ganesan S, Karlsson MCI, Kehrl JH. LRRK2 is required for CD38-mediated NAADP-Ca2+ signaling and the downstream activation of TFEB (transcription factor EB) in immune cells. Autophagy. 2022 Jan;18(1):204-222.

Zhao W, Shi CS, Harrison K, Hwang IY, Nabar NR, Wang M, Kehrl JH. AKT Regulates NLRP3 Inflammasome Activation by Phosphorylating NLRP3 Serine 5. J Immunol. 2020 Oct 15;205(8):2255-2264.

Shi CS, Nabar NR, Huang NN, Kehrl JH. SARS-Coronavirus Open Reading Frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes. Cell Death Discov. 2019 Jun 5;5:101.

Shi CS, Qi HY, Boularan C, Huang NN, Abu-Asab M, Shelhamer JH, Kehrl JH. SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J Immunol. 2014 Sep 15;193(6):3080-9.

Shi CS, Shenderov K, Huang NN, Kabat J, Abu-Asab M, Fitzgerald KA, Sher A, Kehrl JH. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat Immunol. 2012 Jan 29;13(3):255-63.

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