# Molecular control of CD4 T cell ability to help B cells

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $177,120

## Abstract

Project Summary/Abstract:
This proposal details a five-year research and training plan with a scientific focus on a newly discovered
population of T cells, termed `T peripheral helper' (Tph) cells, that is markedly expanded in the joints of patients
with rheumatoid arthritis. The candidate led a study that identified and defined this CD4+ T cell subset (Rao et
al, Nature, 2017). Tph cells display a unique capacity to infiltrate inflamed tissues and drive B cell responses
within the tissue. The long-term objective of the proposed study is to understand signals that regulate the
development and function of Tph cells in the hope of discovering pathways that can be manipulated
therapeutically to treat autoimmune diseases.
The specific aims proposed here utilize three complementary approaches to evaluate the regulation of Tph
cells. Aim 1 will determine conditions that drive human T cell differentiation towards a Tph cell phenotype. Aim
2 interrogates the control of Tph cell function by 3 compelling transcriptional regulators that are overexpressed
in Tph cells. Aim 3 evaluates the developmental relationship of Tph cells in RA synovial tissue samples with
other synovial T cell populations, including T follicular helper cells.
Using a combination of mechanistic studies, patient-derived samples, and cutting-edge technologies, this study
will provide the candidate with new training in several key aspects of human translational immunology. The
candidate's immediate career development goals are to gain experience with bioinformatic and biostatistical
analyses, interpretation of transcriptomic data, genomic manipulation of primary human cells, and scientific
communication. A specific career development plan is described by both the candidate and the mentors: Dr.
Michael Brenner MD, an expert in lymphocyte biology and synovial inflammation, and Dr. Soumya
Raychaudhuri MD PhD, an expert in bioinformatics, capitalizing on the powerful resources at Brigham and
Women's Hospital and Harvard Medical School. The candidate's long-term career goal is to attain a tenure-
track faculty position pursuing research that integrates high-dimensional analyses of patient samples with
detailed mechanistic analyses to develop new methods to diagnose and treat rheumatic diseases.

## Key facts

- **NIH application ID:** 9878058
- **Project number:** 5K08AR072791-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Deepak Angara Rao
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,120
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878058

## Citation

> US National Institutes of Health, RePORTER application 9878058, Molecular control of CD4 T cell ability to help B cells (5K08AR072791-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878058. Licensed CC0.

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