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In silico screening for immune surveillance adaptation in cancer using Common Fund data resources

Award Number: R03OD036494
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2023
PERIOD OF PERFORMANCE END DATE: 09/19/2025

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In silico screening for immune surveillance adaptation in cancer using Common Fund data resources - Summary/Abstract Advances in immunotherapy have lately revolutionized cancer care. A key strategy of cancer immunotherapy is to target “non-cell-autonomous” mechanisms of immune surveillance adaptation, achieved via regulating the secretions of immune modulators from cancer cells. Yet, an in silico systematic screen for these targets and immunomodulating agents (potentially therapeutic drugs) remains untested due to a lack of computational tools to analyze relevant large-scale database resources. The study is proposed in response to RFA-RM-23-003 to meaningfully integrate multiple NIH Common Fund and other NIH-funded datasets to inform the molecular basis of immune surveillance adaptation and screen for potential immunomodulating agents. Our central hypothesis is that cancer genomic features captured by deep learning predict cancer cells’ non-cell autonomous signals induced by a compound treatment to modulate immune cells in the tumor microenvironment. We propose to test the hypothesis by developing an innovative and feasible computational framework that is built upon our published deep learning models. Specifically, in Aim 1.1 we propose to identify prognosis-related immune cell types and associated immunologic gene signatures among adult (The Cancer Genome Atlas [TCGA]) and pediatric tumors (Gabriella Miller Kids First [Kids First] and Therapeutically Applicable Research To Generate Effective Treatments [TARGET]). We will then build a deep learning model to predict the perturbation of the identified immunologic gene signatures induced by a compound in a cancer cell line using the Library of Integrated Network-based Cellular Signatures (LINCS) data. In Aim 1.2, we will experimentally validate key findings using our in-house in vitro models. We have formed a cross-disciplinary team with strong complementary expertise to efficiently achieve the proposed goals: dry lab of Dr. Yu-Chiao Chiu (MPI) for cancer bioinformatics, multi-modal data integration, and artificial intelligence; and wet lab of Dr. Yi-Nan Gong (MPI) for cancer immunology, immunotherapy, and tumor cell death mechanisms. Successful completion of the pilot study will produce high- impact preliminary results: i) the first deep learning framework that systematically incorporates multi-modal genomic and pharmacogenomic data to screen for immunomodulating agents, ii) a deeper understanding of the molecular basis of immune surveillance adaptation than was previously possible, and more importantly iii) a set of promising targets preliminarily validated in vitro. These preliminary data will lead to a follow-up study to explore functional and preclinical aspects of our results. We also expect the proposed study to provide a computational framework that enhances the utilization and integration of NIH Common Fund data and other publicly available large datasets.


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 = -$1,116 )
2026	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Trans-NIH Research Support	000	1	1/28/2026	NEW	-$1,116
														Subtotal = -$1,116

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Trans-NIH Research Support	000	1	10/22/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $318,000 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Trans-NIH Research Support	000	1	9/20/2023	NEW	$318,000
														Subtotal = $318,000

Grand Total All Awards = $316,884

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In silico screening for immune surveillance adaptation in cancer using Common Fund data resources

Award Number: R03OD036494

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/20/2023

PERIOD OF PERFORMANCE END DATE: 09/19/2025

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