Autoimmune rheumatic diseases, which constitute a broad range of chronic illnesses, cause significant morbidity and mortality in the US and worldwide. T cell antigen receptor (TCR) recognition and signaling have long be recognized to play a critical role in the pathogenesis of autoimmune diseases. However, how altered TCR signaling strength affects immune tolerance and promotes autoimmunity remains incompletely understood. The major goal of Dr. Shen’s laboratory is to understand how abnormal TCR signaling resulting from mutations from human patients with immune dysregulated disorders may alter T cell antigen sensitivity and impair immune tolerance. Studying human monogenic diseases with known genetic defects and autoimmune phenotypes provides us with a unique opportunity for advancing our knowledge of disease pathogenesis of more common polygenic autoimmune diseases. These studies may also have implications in preventing cancer immunotherapy related adverse events and identification of new therapeutic targets for autoimmune diseases.
Peking Union Medical College
MD
Johns Hopkins University School of Medicine
PhD
University of Pittsburgh Medical Center
Residency
University of California, San Francisco
Rheumatology Fellowship
ZAP70, too little, too much can lead to autoimmunity.
ZAP70, too little, too much can lead to autoimmunity. Immunol Rev. 2022 05; 307(1):145-160.
PMID: 34923645
Cbl-b deficiency prevents functional but not phenotypic T cell anergy.
Cbl-b deficiency prevents functional but not phenotypic T cell anergy. J Exp Med. 2021 07 05; 218(7).
PMID: 33974042
A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands.
A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands. Sci Signal. 2021 02 02; 14(668).
PMID: 33531381
ZAP-70 in Signaling, Biology, and Disease.
ZAP-70 in Signaling, Biology, and Disease. Annu Rev Immunol. 2018 04 26; 36:127-156.
PMID: 29237129
A quantitative basis for antiretroviral therapy for HIV-1 infection.
A quantitative basis for antiretroviral therapy for HIV-1 infection. Nat Med. 2012 Feb 19; 18(3):446-51.
PMID: 22344296
A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs.
A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs. Sci Transl Med. 2011 Jul 13; 3(91):91ra63.
PMID: 21753122
Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance.
Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance. Proc Natl Acad Sci U S A. 2011 May 03; 108(18):7613-8.
PMID: 21502494
Consistent inhibition of HIV-1 replication in CD4+ T cells by acyclovir without detection of human herpesviruses.
Consistent inhibition of HIV-1 replication in CD4+ T cells by acyclovir without detection of human herpesviruses. J Virol. 2011 May; 85(9):4618-22.
PMID: 21325417
Discovery of entry inhibitors for HIV-1 via a new de novo protein design framework.
Discovery of entry inhibitors for HIV-1 via a new de novo protein design framework. Biophys J. 2010 Nov 17; 99(10):3445-53.
PMID: 21081094
Unstimulated primary CD4+ T cells from HIV-1-positive elite suppressors are fully susceptible to HIV-1 entry and productive infection.
Unstimulated primary CD4+ T cells from HIV-1-positive elite suppressors are fully susceptible to HIV-1 entry and productive infection. J Virol. 2011 Jan; 85(2):979-86.
PMID: 21068257