# The Role of PPARgamma in Th2 cells and Obesity-Associated Asthma.

> **NIH NIH K38** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $113,519

## Abstract

PROJECT SUMMARY/ABSTRACT
 Obesity is a major public health challenge in the United States and worldwide. The chronic complications
and comorbidities from obesity represent one of the greatest challenges to human health. Recent clinical and
epidemiological studies have demonstrated the development of asthma to be strongly associated with obesity.
In fact, obese asthma patients tend to have increased severity of disease and respond poorly to conventional
asthma medications, including corticosteroids. Altogether these observations suggest that obesity-associated
asthma may have a distinct molecular pathophysiology compared to other forms of asthma.
 As such, my long-term research goal is to elucidate the molecular, cellular, and physiological
mechanisms that potentiate obesity-associated asthma in order to identify novel therapeutic approaches for the
management of this disease. The objective of this proposal is to determine the role of the nuclear hormone
receptor PPARg (peroxisome proliferator activated receptor gamma) in TH2 cell effector function and obesity-
associated asthma. In previous work, I have discovered that PPARg functions as a brake on TH2 effector function
and that the restraint is abolished in the obese state. My central hypothesis is that obesity dysregulates PPARg in
TH2 cells to potentiate TH2 cell-driven asthma. I will test this hypothesis using two specific aims. In Aim 1, I will
map the PPARg cistrome in TH2 cells isolated directly from the lungs of lean and obese mice being challenged
with experimental asthma to determine if and how the direct and indirect gene targets of PPARg change with
changes in metabolic state. I will also map the PPARg cistrome in in vitro differentiated human TH2 cells. In Aim
2, using lean and obese mice whose T cells are sufficient or deficient in PPARg, I will determine the role of T
cell-specific PPARg in the development of obesity-associated asthma.
 I am an M.D., Ph.D.-trained clinical pathologist working as a UCSF StARR Scholar at the University of
California, San Francisco. I am applying for the K38 Award to support my goal of becoming an independent
physician scientist. UCSF's exceptional training environment, especially in the fields of immunology, obesity, and
asthma, will support my efforts in this regard. Critical elements of my career development plan include mentorship
by Dr. Alexander Marson, an expert in utilizing functional genomics approaches to investigate T cell biology in
mouse and human; co-mentorship by Dr. Richard Locksley, an expert in Type 2 immunity, helper T cell
development, and in vivo immunology; co-mentorship by Dr. John Fahy, an expert in translational asthma
research with expertise in obesity-associated asthma; guidance by a multidisciplinary advisory committee which
include senior physician-scientists; coursework in data science (R programing), biostatistics, and research
ethics; and professional development activities. Taken together, this career development plan ...

## Key facts

- **NIH application ID:** 10242921
- **Project number:** 5K38HL154202-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Sagar Pradeep Bapat
- **Activity code:** K38 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $113,519
- **Award type:** 5
- **Project period:** 2020-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242921

## Citation

> US National Institutes of Health, RePORTER application 10242921, The Role of PPARgamma in Th2 cells and Obesity-Associated Asthma. (5K38HL154202-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242921. Licensed CC0.

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