Immune defense requires the capacity to respond to ever-changing pathogens and cancers while remaining tolerant to self. The Koh lab focuses on understanding the design principles in immune development that allow flexibility in cellular fate and function, and how these mechanisms are subverted in human disease. A major emphasis is to identify determinants that allow thymic epithelia to ectopically express thousands of tissue-specific self-antigens (e.g. insulin) to promote tolerance against harmful self-reactive T cells and prevent autoimmunity (e.g. diabetes). Another focus is to understand how T cells acquire competence to deploy diverse arrays of effector functions, and how this plasticity relates to leukemogenesis. We employ a broad, interdisciplinary approach combining genetics, genomics, biochemistry and proteomics, with particular investment in developing multi-omics methods to interrogate chromatin accessibility, gene expression, and cell-surface proteins from the same single cell. Elucidating how cellular plasticity is programmed in development, and dysregulated in disease, will avail novel therapeutic avenues for human disorders.
Stanford University
Postdoc - Chromatin Remodeling
2018
Harvard University
PhD - Immunology
2010
University of California, Los Angeles
BS - Molecular, Cell and Developmental Biology
2003
Venetoclax Induces BCL-2-Dependent Treg to TH17 Plasticity to Enhance the Antitumor Efficacy of Anti-PD-1 Checkpoint Blockade.
Venetoclax Induces BCL-2-Dependent Treg to TH17 Plasticity to Enhance the Antitumor Efficacy of Anti-PD-1 Checkpoint Blockade. Cancer Immunol Res. 2024 Aug 01; 12(8):1074-1089.
PMID: 38810242
Publisher Correction: PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.
Publisher Correction: PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape. Nat Immunol. 2024 Jun; 25(6):1123.
PMID: 38755325
The CD8+ T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects.
The CD8+ T cell tolerance checkpoint triggers a distinct differentiation state defined by protein translation defects. Immunity. 2024 06 11; 57(6):1324-1344.e8.
PMID: 38776918
PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.
PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape. Nat Immunol. 2024 May; 25(5):860-872.
PMID: 38632339
AIRE in context: Leveraging chromatin plasticity to trigger ectopic gene expression.
AIRE in context: Leveraging chromatin plasticity to trigger ectopic gene expression. Immunol Rev. 2022 01; 305(1):59-76.
PMID: 34545959
Rapid chromatin repression by Aire provides precise control of immune tolerance.
Rapid chromatin repression by Aire provides precise control of immune tolerance. Nat Immunol. 2018 02; 19(2):162-172.
PMID: 29335648
Global relevance of Aire binding to hypomethylated lysine-4 of histone-3.
Global relevance of Aire binding to hypomethylated lysine-4 of histone-3. Proc Natl Acad Sci U S A. 2010 Jul 20; 107(29):13016-21.
PMID: 20615959
Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity.
Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci U S A. 2008 Oct 14; 105(41):15878-83.
PMID: 18840680
Leukemia & Lymphoma Society Fellow
2011 - 2014
Certificate of Excellence and Distinction in Teaching
Harvard College
2006 - 2007
NIH Ruth L. Kirschstein National Research Service Award
2006 - 2008