# Padmanabhan K08 Admin Supplement

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $75,600

## 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 was 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. With an
unusual degree of irony, I suffered a myocardial infarction in October, 2022 that was complicated by a
diagnosis of HF which has slowed my progress in carrying out the aims described in my initial proposal. I am
hopeful that the additional funding afforded by this Administrative Supplement will allow me to close the gap in
productivity that resulted from this critical life event. Those aims are centered around the hypotheses that 1.)
the ubiquitously expressed chromatin reader protein BRD4 complexes with the cardiac transcription factor
GATA4 to regulate mitochondrial bioenergetic gene programs in cardiomyocytes; 2.) 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; and 3.) that a BRD4-GATA4 module controls the expression of
PGC-1a and b, known master transcriptional regulators of mitochondrial genes, to mediate the phenotype of
cardiomyocyte BRD4 loss. To address those aims, I have been combining novel animal models that I have
generated, standard in vitro biochemical approaches, and advanced molecular biology and bioinformatics
techniques. My long-term goal, which is now further motivated by my personal experience with this chronic
disease, 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 inve...

## Key facts

- **NIH application ID:** 10852749
- **Project number:** 3K08HL157700-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Arun Padmanabhan
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $75,600
- **Award type:** 3
- **Project period:** 2021-07-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10852749

## Citation

> US National Institutes of Health, RePORTER application 10852749, Padmanabhan K08 Admin Supplement (3K08HL157700-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10852749. Licensed CC0.

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