# Decoding the nuclear metabolic processes regulating gene transcription

> **NIH NIH DP2** · ROSWELL PARK CANCER INSTITUTE CORP · 2024 · $20,175

## Abstract

In this High Risk High Reward DP2 application I wish to investigate the nuclear functions of mitochondrial
metabolic enzymes. It is quite evident from current literature that many of the mitochondrial enzymes are
localized to the nucleus, more so in diseased conditions such as cancer. However, there is a significant gap in
knowledge about their spatial distribution in the nucleus and biological function. We believe nuclear localization
of mitochondrial metabolic enzymes is not random, and there is specific necessity coupled to critical biological
functions that regulate this process. In this study we wish to perform a comprehensive functional
characterization deciphering the spatial and temporal role of mitochondrial enzymes in the nucleus. Our
preliminary findings identified Kreb’s cycle enzymes such as aconitase (ACO2), α-keto glutarate (AKG), and
citrate synthase (CS); and glycolytic enzymes such as pyruvate dehydrogenase (PDH) and ATP-citrate lyase
are enriched in the nucleus of cancer cells. We hypothesize these mitochondrial enzymes form complex in the
nucleus based which is yet to be characterized. We hypothesize that they function as a large-multi enzyme
complex which is recruited to chromatin by transcription factors and coregulators to sustain metabolic stress
encountered during gene transcription. Using metabolomics, proteomics, chromatin immunoprecipitation and
gene expression analysis, we envision detailing the sequential events driving their recruitment by nuclear
factors on chromatin, and their role in reprogramming transcription machinery to drive aggressive cancer. This
is a novel concept supported by isolated reports from various groups, yet remains relatively unexplored and a
comprehensive mechanistic study is lacking. We envision findings from our study will have a major impact on
broad important problems in biomedical research including metabolic disorders and cancer.

## Key facts

- **NIH application ID:** 10818770
- **Project number:** 3DP2CA260421-01S1
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Subhamoy Dasgupta
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $20,175
- **Award type:** 3
- **Project period:** 2023-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818770

## Citation

> US National Institutes of Health, RePORTER application 10818770, Decoding the nuclear metabolic processes regulating gene transcription (3DP2CA260421-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10818770. Licensed CC0.

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