# Differences in RNA and miRNA expression in response to MC and DMC stereoisomeric interstrand crosslinks (Student: Christina Gonzalez)

> **NIH NIH SC3** · JOHN JAY COLLEGE OF CRIMINAL JUSTICE · 2022 · $96,082

## Abstract

Summary:
The overarching goal of the parent proposal for this “research supplement to promote diversity in
health-related research” is to investigate the relationship between the structure of stereoisomeric
DNA Interstrand Crosslinks (ICLs) formed by Mitomycin C and Decarbamoylmitomycin C and the
molecular mechanisms of these drugs. Mitomycin C (MC) is an anticancer drug currently used to
treat stomach, anal and lung cancers. The stereochemical configuration at C1’’ of MC major ICL
is R (α-ICL). In contrast, Decarbamoylmitomycin C (DMC), a derivative of MC lacking the O10
carbamoyl group, generates the S stereoisomeric ICL (β-ICL). The scientific premise of the
proposed research is that ICLs constitute the molecular basis for the cytotoxic effects of
mitomycins. The central hypothesis is that differences in the local DNA structures of the α and β-
ICLs are responsible for the distinct biochemical responses triggered by MC and DMC. In
particular, contrary to MC, the DNA-adducts generated by DMC treatment (-ICL) rapidly activate
a p53-independent cell death pathway. Thus, the study MC-DMC provides an ideal model for
identifying structural features determining the cell signaling outcome in the presence or the
absence of a functioning p53 pathway. Since p53 tumor suppressor is frequently mutated in
human cancers, the need to identify drugs and pathways that induce cell death or cell cycle arrest
independently of p53 deserves substantial attention. Within the scope of the parent project, this
supplement to promote diversity in health-related research will be used to train the candidate,
Christina Gonzalez to: 1: Synthesize oligonucleotides containing α/β ICLs; 2: Transfect cells with
these oligonucleotides; 3: Perform RNA extraction to determine the changes to gene expression
profiles in the cellular response after transfection of the α or β-ICL; 4: Determine changes to
microRNA (miRNA) profiles in the cellular response to MC/DMC exposure; 5: Identify how these
drugs impact functional miRNAs and if MC/DMC-miRNAs adducts are formed; and 6: Gain skills
in bioinformatic analysis of transcriptomics data. Christina’s long-term goal is to become a medical
research scientist. The training and activities proposed will improve Christina’s chances to access
MD-PHD programs by fostering crucial technical and professional skills. To further enhance
Christina’s competitiveness, she will work closely with our collaborator, Dr Sanchez-Vega, head
of the Computational Biology Division at Memorial Sloan Kettering Cancer Center Colorectal
Cancer Unit. She will also receive career advisement from Dr Edgardo Sanabria-Valentin, the
PRISM Associate Program Director and Pre-Health Career Advisor.

## Key facts

- **NIH application ID:** 10544084
- **Project number:** 3SC3GM105460-08S3
- **Recipient organization:** JOHN JAY COLLEGE OF CRIMINAL JUSTICE
- **Principal Investigator:** Elise Champeil
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $96,082
- **Award type:** 3
- **Project period:** 2014-07-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10544084

## Citation

> US National Institutes of Health, RePORTER application 10544084, Differences in RNA and miRNA expression in response to MC and DMC stereoisomeric interstrand crosslinks (Student: Christina Gonzalez) (3SC3GM105460-08S3). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10544084. Licensed CC0.

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