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Quantitative top-down proteomics of human colorectal cancer cells and tumors

Award Number: R01CA247863
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/10/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Quantitative top-down proteomics of human colorectal cancer cells and tumors - Project Summary It has been estimated that 145,600 people were diagnosed with colorectal cancer (CRC) and 51,020 deaths were predicted due to this disease in 2019 (https://seer.cancer.gov/statfacts/html/colorect.html). A better understanding of CRC at the molecular level will certainly lead to therapies that are more effective. The genome- level and transcriptome-level information cannot accurately reflect the protein-level information because post-transcriptional regulation can modulate protein expression and because post-translational modifications (PTMs) can influence protein function. Quantitative proteomic studies of CRC are vital. Many bottom-up proteomics studies have been completed on CRC cells and tumors, but limited information on proteoforms have been acquired due to low protein sequence coverages typically obtained from bottom-up proteomics. Different proteoforms from the same gene can have drastically different functions. We hypothesize that large-scale and quantitative top-down proteomics of human CRC cells and tumors will provide new insights into CRC, leading to better therapies. In this proposal, we will develop new analytical tools to boost the sensitivity and scale of top-down proteomics. The new tools will enable large-scale and quantitative top-down proteomics of CRC cells before and after metastasis as well as CRC tumors from patients with Lynch Syndrome. Results from this proposal are extremely important. The novel analytical tools will boost the sensitivity of top-down proteomics by tenfold and will be particularly useful for the proteomics community for large-scale top-down proteomics of mass-limited samples. Quantitative top-down proteomics of CRC cells before and after metastasis will generate an unprecedented resource for the cancer biology community to gain new insights into CRC metastasis. Quantitative top-down proteomics of the Lynch Syndrome tissues will elucidate the roles played by mutations and functions of DNA mismatch repair genes in Lynch Syndrome at the proteoform level.


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: 2026 ( Subtotal = $0 )
2026	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 360	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	5	11/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $392,016 )
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	5	12/23/2024	NON-COMPETING CONTINUATION	$352,815
2025	2025	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	001	5	6/11/2025	NON-COMPETING CONTINUATION	$39,201
														Subtotal = $392,016

Issue Date FY: 2024 ( Subtotal = $422,165 )
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	002	4	9/4/2024	NON-COMPETING CONTINUATION	$50,000
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	4	1/25/2024	NON-COMPETING CONTINUATION	$352,577
2024	2024	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	001	4	4/18/2024	NON-COMPETING CONTINUATION	$19,588
														Subtotal = $422,165

Issue Date FY: 2023 ( Subtotal = $365,244 )
2023	2023	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	3	1/31/2023	NON-COMPETING CONTINUATION	$365,244
														Subtotal = $365,244

Issue Date FY: 2022 ( Subtotal = $363,183 )
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	2	1/17/2022	NON-COMPETING CONTINUATION	$333,536
2022	2022	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	001	2	5/24/2022	NON-COMPETING CONTINUATION	$29,647
														Subtotal = $363,183

Issue Date FY: 2021 ( Subtotal = $401,634 )
2021	2021	MICHIGAN STATE UNIVERSITY	426 AUDITORIUM RD RM 2	EAST LANSING	MI	48824	INGHAM	USA	Cancer Biology Research	000	1	2/9/2021	NEW	$401,634
														Subtotal = $401,634

Grand Total All Awards = $1,944,242

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Quantitative top-down proteomics of human colorectal cancer cells and tumors

Award Number: R01CA247863

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/10/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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