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

Award Number: SC3GM105460
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2014
PERIOD OF PERFORMANCE END DATE: 07/31/2023

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = -$7,709 )
2024	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	001	8	4/11/2024	SUPPLEMENT FOR EXPANSION	-$4,211
2024	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	8	4/11/2024	NON-COMPETING CONTINUATION	-$3,498
														Subtotal = -$7,709

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	8	7/30/2023	NON-COMPETING CONTINUATION	$0
2023	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	002	8	8/24/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	003	8	8/24/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	001	8	8/24/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $265,193 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	002	8	4/5/2022	SUPPLEMENT FOR EXPANSION	$4,764
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	8	3/25/2022	NON-COMPETING CONTINUATION	$108,311
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	001	8	4/4/2022	SUPPLEMENT FOR EXPANSION	$44,001
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	004	8	6/20/2022	NON-COMPETING CONTINUATION	$12,035
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	003	8	6/13/2022	SUPPLEMENT FOR EXPANSION	$96,082
														Subtotal = $265,193

Issue Date FY: 2021 ( Subtotal = $206,303 )
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	003	7	7/22/2021	SUPPLEMENT FOR EXPANSION	$31,689
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	002	7	7/21/2021	SUPPLEMENT FOR EXPANSION	$31,689
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	001	7	7/20/2021	SUPPLEMENT FOR EXPANSION	$22,733
2021	2021	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	7	3/24/2021	NON-COMPETING CONTINUATION	$120,192
														Subtotal = $206,303

Issue Date FY: 2020 ( Subtotal = $120,043 )
2020	2020	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	6	4/23/2020	NON-COMPETING CONTINUATION	$120,043
														Subtotal = $120,043

Issue Date FY: 2019 ( Subtotal = $119,886 )
2019	2019	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	001	5	4/10/2019	COMPETING CONTINUATION	$119,898
2019	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	4	11/25/2018	NON-COMPETING CONTINUATION	-$12
														Subtotal = $119,886

Issue Date FY: 2017 ( Subtotal = $119,722 )
2017	2017	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	524 W 59TH ST	NEW YORK	NY	10019	NEW YORK	USA	Biomedical Research and Research Training	000	4	6/21/2017	NON-COMPETING CONTINUATION	$119,722
														Subtotal = $119,722

Issue Date FY: 2016 ( Subtotal = $112,999 )
2016	2016	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Biomedical Research and Research Training	000	3	7/1/2016	NON-COMPETING CONTINUATION	$112,999
														Subtotal = $112,999

Issue Date FY: 2015 ( Subtotal = $113,028 )
2015	2015	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Biomedical Research and Research Training	000	2	6/16/2015	NON-COMPETING CONTINUATION	$113,028
														Subtotal = $113,028

Issue Date FY: 2014 ( Subtotal = $118,112 )
2014	2014	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Biomedical Research and Research Training	000	1	4/10/2014	NEW	$118,112
2014	2014	CUNY, RESEARCH FOUNDATION	230 WEST 41ST STREET	NEW YORK	NY	10036	NEW YORK	USA	Biomedical Research and Research Training	001	1	5/22/2014	NEW	$0
														Subtotal = $118,112

Grand Total All Awards = $1,167,577

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

Award Number: SC3GM105460

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2014

PERIOD OF PERFORMANCE END DATE: 07/31/2023

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