# Signaling and repertoire differences in arthritogenic T cells

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $177,498

## Abstract

PROJECT SUMMARY/ ABSTRACT
 This multidisciplinary, 5-year K08 application is designed to facilitate the career development of Dr. Judith F.
Ashouri, MD, an Assistant Professor in Rheumatology at UCSF, as an independent physician-scientist. Dr.
Ashouri specializes in rheumatoid arthritis (RA). After receiving training in Rheumatology and Immunology at
UCSF, she now seeks to further develop her research experience to attain her long-term goal of becoming an
independent investigator, dissecting the contribution of antigen (Ag)-specific, pathogenic CD4 T cells to arthritis
development in RA. This K08 award will provide Dr. Ashouri with the support and protected time necessary to
accomplish the following objectives: (1) to improve advanced immunology skills including immunophenotyping
using mass cytometry and T cell receptor (TCR) sequencing,(2) to become proficient in advanced statistical
analyses using RNAseq data sets, (3) to acquire skills critical for an academic career including scientific writing
and oral presentation, and (4) to submit an R01 application during year 5 of the proposed grant. The candidate
has assembled an exceptionally strong advisory team of experts in Basic/Translational Immunology and
Autoimmunity—all of whom have successfully mentored many young scientists. Her career development plan
includes regular meetings with her mentors, didactics, and attendance at local and national meetings. UCSF, a
world-class institution with particular strengths in immunology, translational research, and autoimmunity, is the
ideal environment for developing her career.
 RA afflicts millions globally and is without cure. CD4 T cells are known to play a key role in RA
pathogenesis. Yet, it remains unknown how arthritis-causing T cells initiate disease and to what Ag these T
cells respond. T cells can either be activated through their TCR in an Ag-specific manner, or in response to
cytokines. Identification of Ag-activated T cells in RA would allow us to investigate arthritogenic clones and
elucidate early events in disease pathogenesis. However, isolating relevant arthritogenic TCR-activated T cells
(as opposed to `bystander' T cells activated by the inflammatory milieu) has limited the field's understanding of
disease-initiating events in RA. Dr. Ashouri and colleagues have pioneered a new strategy to overcome this
limitation. In this proposal, she builds on preliminary data that demonstrate the ability to track Ag-specific,
arthritogenic T cell responses in RA in both a mouse model of RA (SKG mice) and human RA joint tissue.
Tracking these arthritis causing T cells will facilitate Dr. Ashouri's (a) short term goal to identify and study
arthritis-causing T cells before and during RA disease development and (b) long term goal to identify the
inciting Ag(s). Successful completion of the proposed studies will provide new mechanistic insights of how
arthritis-causing CD4 T cells contribute to destructive RA and holds promise for improved therapeutic...

## Key facts

- **NIH application ID:** 10456953
- **Project number:** 5K08AR072144-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Judith Ashouri
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $177,498
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456953

## Citation

> US National Institutes of Health, RePORTER application 10456953, Signaling and repertoire differences in arthritogenic T cells (5K08AR072144-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456953. Licensed CC0.

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