# A BRD4-GATA4 module cooperatively regulates mitochondrial bioenergetic homeostasis in the adult heart

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $150,881

## Abstract

PROJECT SUMMARY / ABSTRACT
Heart failure (HF) affects millions of people and costs over 40 billion dollars annually in the United States
alone. Despite current pharmacotherapeutic approaches, which largely involve blockade of circulating
neurohormone activity, a diagnosis of HF carries a 5‐year mortality rate of nearly 50% underscoring the urgent
need for new treatments. The mitochondria have emerged as a central factor in the pathogenesis and
progression of HF with no therapies presently available to address mitochondrial dysfunction.
My goal in seeking a K08 Mentored Clinical Scientist Research Career Development Award is to acquire
the necessary knowledge and practical training to make major advances in our understanding of the
mechanisms underlying cardiac energy metabolism and mitochondrial function in the adult heart. I hypothesize
that BRD4 (a ubiquitously expressed chromatin “reader” protein) complexes with GATA4 (a lineage
determining cardiac transcription factor) to regulate a mitochondrial bioenergetic gene program in
cardiomyocytes (Aim 1). I also hypothesize that GATA4 is a critical regulator of cardiac metabolism in
cardiomyocytes in vivo and that this tissue-enriched transcription factor is providing specificity to the action of
BRD4 (Aim 2). Finally, I hypothesize that a BRD4-GATA4 module controls the expression of PGC-1α and β,
known master transcriptional regulators of mitochondrial genes, to mediate the phenotype of cardiomyocyte
BRD4 loss (Aim 3). To address these aims, I will combine novel animal models that I have generated, standard
in vitro biochemical approaches, and advanced molecular biology and bioinformatics techniques. My long-term
goal is to develop a deeper molecular understanding of HF pathogenesis that may lead to novel therapies.
My graduate training provided me with important experience in cardiovascular research, however my focus
was on developmental biology. I am now directing my efforts towards studying adult cardiomyocyte
homeostasis—an area of interest that emerged from my clinical training in cardiology. My research mentor has
a long record of impactful discoveries using cutting-edge techniques in cellular and animal models of
cardiovascular disease. The research environment at the Gladstone Institutes/UCSF is exceptional and houses
state-of-the-art equipment and investigators making groundbreaking discoveries. I have assembled a team of
highly accomplished mentors and advisors to guide me through this next phase of my training on the path to
becoming an independent investigator. My training plan is specifically designed to provide me with mentorship
and research training in bioinformatics, mouse modeling of disease, and advanced techniques in molecular
biology. Beyond this, I will gain experience with other skills required to run a research group, such as scientific
communication and laboratory management. Completing the research and obtaining the skill sets outlined in
this proposal will prepare me well...

## Key facts

- **NIH application ID:** 10190564
- **Project number:** 1K08HL157700-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Arun Padmanabhan
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $150,881
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190564

## Citation

> US National Institutes of Health, RePORTER application 10190564, A BRD4-GATA4 module cooperatively regulates mitochondrial bioenergetic homeostasis in the adult heart (1K08HL157700-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190564. Licensed CC0.

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