# Axes of Oncometabolism in the Heart

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $385,000

## Abstract

Summary
 In the heart, as in cancer, metabolism provides energy and building blocks for the cell. James Watson (of
The Double Helix fame) recently pronounced that in cancer, targeting metabolism may be a more promising
approach to treatment than targeting transforming genes. At a time when cellular regeneration receives much
attention, the intracellular dynamics of metabolism must be considered as well. In earlier work supported by
this grant, we identified two metabolic signals serving as regulators of protein turnover in the heart: a low
[ATP] / [AMP] ratio as regulator for protein degradation, and glucose 6-phosphate as regulator of the mTOR
growth signaling pathway. We learned that in the heart, like in cancer cells, a phenomenon known as the
Warburg Effect drives metabolic rearrangements which are linked to enable cell growth. Perhaps even more
importantly, we learned that the oncometabolite D-2-hydroxyglutarate impairs cardiac function by inhibiting a
Krebs cycle enzyme. Our overall objective is now to solidify the concept of a link between cancer cell
metabolism, and cardiac cell metabolism, cardiac structure, and cardiac function independently from
any chemotherapeutic agents or pharmacological interventions. Specific Aim 1 will define the role of
oncometabolic signals as regulators of cardiac remodeling. Specific Aim 2 will define the role of reductive
carboxylation as a mediator for metabolic structural and functional remodeling of the heart using the
oncometabolite D-2-hydroxyglutarate as a model. Specific Aim 3 will extend the findings to address specific
structural, proteomic and epigenetic mechanisms of remodeling in the metabolically deregulated state of D-2-
hydroxyglutarate. In summary, as we continue our work on the intracellular self-renewal of the cardiomyocyte,
we expect to identify new regulatory proteins and enzymes that drive adaptation to metabolic stress in the
heart. Our long-term goal is to develop a platform for new metabolic strategies to support the failing human
heart by integrating specific, dynamic aspects of cancer cell metabolism with heart metabolism. In short,
metabolic systems do not exist in isolation and their understanding may be exploited for the treatment of heart
failure.

## Key facts

- **NIH application ID:** 10070632
- **Project number:** 5R01HL061483-18
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** HEINRICH TAEGTMEYER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 1999-01-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070632

## Citation

> US National Institutes of Health, RePORTER application 10070632, Axes of Oncometabolism in the Heart (5R01HL061483-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070632. Licensed CC0.

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