# Elucidating Molecular Mechanisms of Cancer Development by Investigating Key DNA Repair Pathways

> **NIH NIH K01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $131,595

## Abstract

Project Summary
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Dr. Sharonda LeBlanc earned her PhD in Nanoscale Science, investigating the effects of electric fields on
single quantum dot (SQD) fluorescence emission using confocal microscopy coupled with time-resolved
spectroscopy. She discovered interesting photophysical effects of moderate applied fields and plasmonic films
on SQDs. Dr. LeBlanc is currently transitioning from fundamental physical chemistry to biochemistry/biophysics
while still utilizing single molecule techniques. Currently, she is a postdoctoral researcher at UNC Chapel Hill
investigating molecular interactions of mismatch repair proteins. She works between two labs at UNC
(Chemistry) and NC State (Physics) to complete her research. Her career goal is to obtain a tenure-track
position at a research institution. She would like to combine her past research experience in nanoscience with
biochemistry/biophysics to ultimately investigate molecular mechanisms of cancer development in vivo. The
specific aims of this proposal and research training plan are designed to enhance Dr. LeBlanc's skills and
knowledge in the biological sciences, specifically DNA repair. Specific Aims 1 and 2 are as follows:
Specific Aim 1: Characterize the nucleotide-dependent dynamics of MutL conformations in the
absence of mismatch DNA in vitro using single molecule FRET.
Specific Aim 2: Investigate the dynamics of wild-type and mutant MutL conformations in the context of
mismatch repair initiation with nucleotides, MutS, and mismatch DNA in vitro with smFRET.
DNA mismatch repair (MMR) is a post-replicative system of proteins that corrects rare mistakes in the genome
of all organisms. In the human genome of 6 billion bases, there are ~ 600 errors per round of replication, per
cell. If left uncorrected, errors accumulate as permanent mutations in a genome, and can lead to a disease
state in the organism. MutS and MutL homologs are tasked with recognizing a mismatch in 107 correctly paired
bases, discriminating between parent and daughter strand, then initiating repair. Single amino acid mutations
in MutS and MutL proteins have been linked to hereditary and sporadic colorectal cancer, the third most
common cancer worldwide. Although these mutations, mostly associated with MutL, have been identified in
cancer cases, it is unclear how MMR deficiencies initiate and advance the disease. Failures in the mismatch
repair pathway likely initiate tumorigenesis, but we lack a fundamental understanding of the MMR process.
Single molecule fluorescence resonance energy transfer (smFRET) is uniquely capable of investigating the
molecular mechanism of MMR that involves multiple transient protein-protein and protein-DNA interactions.
These experiments may provide a basis for identifying therapeutic targets. The final aim of this proposal is
designed to facilitate Dr. LeBlanc's transition to an independent career, outlined in the Research Strategy:
Specific Aim 3: Develop ideas, design experiments, and test new hypoth...

## Key facts

- **NIH application ID:** 10241108
- **Project number:** 7K01CA218304-04
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Sharonda LeBlanc
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $131,595
- **Award type:** 7
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241108

## Citation

> US National Institutes of Health, RePORTER application 10241108, Elucidating Molecular Mechanisms of Cancer Development by Investigating Key DNA Repair Pathways (7K01CA218304-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241108. Licensed CC0.

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