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Proteogenomic Characterization of Tumor Tissues and Preclinical Models with High Precision

Award Number: U24CA271079
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Proteogenomic Characterization of Tumor Tissues and Preclinical Models with High Precision - Summary During the last 10 years of both CPTAC2 and CPTAC3, the JHU Proteome Characterization Center (JHU/PCC) has repeatedly demonstrated superior technological innovation and robust data generation that have played critical roles in the success of CPTAC's core mission of accelerating the understanding of the molecular basis of cancer through the application of large-scale proteome and genome analysis technologies to different cancer types. As one of the 3 current CPTAC3 PCCs, we established robust and standardized proteomic analysis protocols and technologies and applied them to 7 human cancer cohorts and an additional 200 patient-derived xenografts from the Patient-Derived Models Repository. Together with the Proteogenomic Data Analysis Centers (PGDACs), we published articles on integrated proteogenomic studies in four cancer types. For our CPTAC4 PCC application, the overarching goal of our PCC is to generate accurate and reproducible data using sensitive, quantitative, and standardized technologies. We will leverage our established Center's infrastructure and capitalize on our success in clinical cancer proteogenomic discoveries to characterize proteins, protein modifications, and protein complexes associated with genomic alterations of cancer from additional human tumor types and pre-clinical models. We will identify unique features that are inherent to proteins such as post-translational modifications covering acetylation and ubiquitination, as well as protein- protein interactions in addition to glycosylation and phosphorylation that have been included in our current PCC. We propose a three-step strategy to characterize defined sets of genomics-characterized samples using technology platforms validated during CPTAC3: (1) Discovery of target proteins from both clinical specimens and preclinical models using quantitative proteomics by tandem mass tags and data dependent acquisition mass spectrometry; (2) Verification of findings using orthogonal data-independent acquisition mass spectrometry; and (3) Confirmation of the verified targets using high-throughput, CPTAC Tier 2 analytically-validated targeted Multiple Reaction Monitoring Mass Spectrometry (MRM-MS) assays. We further propose pilot studies for technology improvement. While this PCC application is focused on the proteomic characterization of clinical specimens and preclinical models, we believe that the understanding of and the expertise in proteogenomic data analysis and translation will be critical for the success of the PCC and the overall CPTAC network. We have assembled a team of outstanding investigators with complementary expertise and years of experience in the CPTAC program (CPTAC2 and CPTAC3), and evidence of successful collaborations with investigators/PIs from the CPTAC PGDACs and Proteogenomic Translational Research Centers (PTRCs). We believe that our PCC offers the best opportunity for the successful characterization of biological and clinical specimens to discover and confirm cancer targets to advance precision cancer medicine.


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: 2025 ( Subtotal = $1,137,216 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	002	4	5/22/2025	NON-COMPETING CONTINUATION	$113,721
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	4	4/28/2025	NON-COMPETING CONTINUATION	$1,023,495
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	003	4	8/21/2025	NON-COMPETING CONTINUATION	$0
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	3	1/1/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,137,216

Issue Date FY: 2024 ( Subtotal = $1,084,866 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	002	3	5/23/2024	NON-COMPETING CONTINUATION	$1,084,866
2024	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	2	12/26/2023	NON-COMPETING CONTINUATION	$0
2024	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	2	11/20/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,084,866

Issue Date FY: 2023 ( Subtotal = $2,101,489 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Trans-NIH Research Support	002	2	6/2/2023	SUPPLEMENT FOR EXPANSION	$982,438
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	2	5/31/2023	NON-COMPETING CONTINUATION	$1,119,051
2023	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	1	1/17/2023	NEW	$0
														Subtotal = $2,101,489

Issue Date FY: 2022 ( Subtotal = $1,157,752 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	001	1	6/8/2022	NEW	$0
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cancer Detection and Diagnosis Research	000	1	5/23/2022	NEW	$1,157,752
														Subtotal = $1,157,752

Grand Total All Awards = $5,481,323

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Proteogenomic Characterization of Tumor Tissues and Preclinical Models with High Precision

Award Number: U24CA271079

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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