# Elucidating and exploiting NAD metabolic defects in cancer

> **NIH NIH K00** · YALE UNIVERSITY · 2024 · $101,003

## Abstract

Project Summary
Lung cancer is the most commonly diagnosed and deadliest cancer in the world, accounting for over nearly
one-fifth of all cancer deaths in 2018, and the 5-year survival rate for non-small cell lung cancer (NSCLC) is
only 18.1%. Given these poor outcomes, new treatment approaches that selectively target cancer cells are
urgently needed. Despite the recent interest in the field of cancer redox metabolism, the link between cancer
redox metabolism and DNA damage repair/signaling as a means by which to enhance tumor cell responses to
radio-chemotherapies remains largely unexplored. My Ph.D. thesis work seeks to exploit inherent differences
in cancer cell NAD+ metabolism to sensitize cancer cells to radio-chemo-therapies. We hypothesize that
selective depletion of NAD(P)(H) in NSCLC cells (versus normal cells) with nicotinamide
phosphoribosyltransferase (NAMPT) inhibitors will confer potent radio-chemo-sensitization by
inducing hydroperoxide-mediated metabolic oxidative stress and/or persistence of cytotoxic PARP-
DNA complexes. My preliminary data supports this hypothesis and, in the remaining F99 phase, a causal link
between the radio-chemo-sensitizing effects of NAMPT inhibition on metabolic oxidative stress and/or
persistent PARP1-DNA complex formation will be established. I will continue by investigating DNA damage
signaling/repair and cancer cell redox metabolism as a post-doctoral researcher studying the relationship
between ataxia telangiectasia mutated (ATM) and dysregulated cancer cell redox metabolism with the goal of
enhancing cancer cell responses to radio-chemotherapies. Overall, I believe that this F99/K00 award will
provide the means for me to utilize my skills as a redox biologist in order to establish a research career
focused on the role of cancer cell redox metabolism and DNA damage repair/signaling in tumor cell responses
to radio-chemotherapies.

## Key facts

- **NIH application ID:** 10839337
- **Project number:** 5K00CA245722-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Collin David Heer
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $101,003
- **Award type:** 5
- **Project period:** 2019-09-20 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10839337

## Citation

> US National Institutes of Health, RePORTER application 10839337, Elucidating and exploiting NAD metabolic defects in cancer (5K00CA245722-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10839337. Licensed CC0.

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