Judith Ashouri Sinha, MD

Assistant Professor in Residence
Medicine
+1 415 476-4116
Research Overview: 

The Ashouri lab is focused on understanding how aberrant immune cell signaling disrupts immune tolerance, resulting in autoimmune (AI) disease.  We are particularly interested in T cell mechanisms that contribute to the onset of rheumatoid arthritis (RA), a debilitating disease affecting millions.  A specific aim of the Ashouri lab is to identify antigen-activated T cells in RA in order to capture and profile arthritogenic clones and elucidate the earliest events in disease pathogenesis.

Our work takes advantage of a specific reporter of T cell antigen receptor (TCR) signaling. Tracking the expression of this reporter of TCR signaling in murine and human T cells facilitates our ability to identify and study arthritis-causing T cells before and during RA disease development and addresses the following questions:

  1. How are T cells that are relatively deficient TCR signaling able to mediate arthritis development?  Our lab uses molecular and biochemical techniques to examine how chronic TCR signaling can enhance T cell sensitivity to cytokine signaling and its dysregulation in disease.
  2. How are arthritis causing CD4 T cells initially triggered in disease and to what antigen do these T cells respond? 

We utilize multi-dimensional and high-throughput technologies including paired single-cell RNA and TCR-sequencing from mouse and human samples with significant potential to identify the TCR specificity, gene expression profile, and signaling networks of cells involved in antigen recognition in RA.  Our model system provides a platform to track antigen-specific T cell responses in human diseases in which the inciting antigen is not known and could be broadly applied to other AI diseases, transplant rejection, cancer, and even checkpoint blockade.

Primary Thematic Area: 
Immunology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Pathogenic Antigen-activated T cells in Autoimmune Disease
Featured Publications: 

Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis.

Proceedings of the National Academy of Sciences of the United States of America

Ashouri JF, Hsu LY, Yu S, Rychkov D, Chen Y, Cheng DA, Sirota M, Hansen E, Lattanza L, Zikherman J, Weiss A

Endogenous Nur77 Is a Specific Indicator of Antigen Receptor Signaling in Human T and B Cells.

Journal of immunology (Baltimore, Md. : 1950)

Ashouri JF, Weiss A

A sharp T-cell antigen receptor signaling threshold for T-cell proliferation.

Proceedings of the National Academy of Sciences of the United States of America

Au-Yeung BB, Zikherman J, Mueller JL, Ashouri JF, Matloubian M, Cheng DA, Chen Y, Shokat KM, Weiss A