# Determining the location and phenotype requirement of CD4 T cells in schistosomiasis pulmonary hypertension

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $54,862

## Abstract

PROJECT SUMMARY / ABSTRACT
 This Supplement will support Ms. Dara Fonseca Balladares for 1 year following completion of her
baccalaureate to help her achieve her career goals of attending medical school in an MD-PhD program, and
becoming an independent physician scientist. This research fellowship will provide Ms. Fonseca Balladares with
technical skills to perform experiments; cognitive skills to plan experiments, interpret results and plan appropriate
next steps; and additional education in research including ethics and immunology (relevant to this research
project now, and her future career in medicine). Ms. Fonseca Balladares will complete a detailed plan of
progressive milestones outlined in the proposal, including acquiring experimental techniques and formulation of
novel hypotheses. She will participate in several career development programs at the University of California
Berkeley and San Francisco, including formal coursework in topics relevant to the research project and her
career goals. She will work with the PI Graham and a pre-identified career development advisory committee,
who will monitor the course of her experimental research plan and career development training. It is expected
that Ms. Fonseca Balladares will present her work at the ATS international conference, and publish a first author
paper reporting her findings obtained in completing the proposed research.
 Ms. Dara Fonseca Balladares’ research project will investigate the phenotype and location requirement of
CD4 T cells in schistosomiasis-induced pulmonary hypertension (PH). The mouse model we use employs
intraperitoneal (IP) sensitization prior to intravenous (IV) challenge with Schistosoma eggs to cause PH, and we
have shown Th2 CD4 T cells are necessary and sufficient for Schistosoma-induced PH, which direct Type 2
inflammation that causes recruitment of Ly6c+ monocytes which express thrombospondin-1 (TSP-1), resulting in
TGF-β activation which induces pathologic phenotypes in the vascular cells. An initial preliminary experiment
suggested that there are activated CD4 T cells in the lungs which do not require migration from lymph nodes to
trigger inflammation-induced PH, as FTY720 which arrests T cells in lymph nodes did not block the PH
phenotype. The supplement hypothesis is thus that primed and pre-positioned T cells in the lung are sufficient
to induce Type 2 immune-driven Schistosoma PH with IV egg challenge. Specific Aim 1 of the supplement will
describe the numbers and phenotype of CD4 T cells in lymph nodes and lung tissue following IP sensitization
and IV egg challenge. Specific aim 2 of the supplement will determine if CD4 T cells already present in the lungs
are sufficient to induce Type 2 immunity and Schistosoma-induced PH. Overall this topic is within the scope of
the parent grant, which seeks to determine the functions of dendritic cells and CD4 T cells which are necessary
for Schistosoma-PH, by now seeking to identify the specific location requireme...

## Key facts

- **NIH application ID:** 10732723
- **Project number:** 3R01HL135872-06S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Brian Barkley Graham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $54,862
- **Award type:** 3
- **Project period:** 2023-02-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10732723

## Citation

> US National Institutes of Health, RePORTER application 10732723, Determining the location and phenotype requirement of CD4 T cells in schistosomiasis pulmonary hypertension (3R01HL135872-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10732723. Licensed CC0.

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