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Single Cell Deconvolution of the Pancreatic Tumor Microenvironment

Award Number: F30CA257489
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/09/2020
PERIOD OF PERFORMANCE END DATE: 12/08/2024

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Single Cell Deconvolution of the Pancreatic Tumor Microenvironment - Project Summary/Abstract: Pancreatic ductal adenocarcinoma (PDAC) maintains its status as one of most lethal solid cancers with a 5-year survival of 8%. Minor improvements have been attributed to early detection, but the vast majority of patients face a grim prognosis without effective therapeutic intervention. Molecular analysis of patient samples has often been confounded by mixed biological samples, leading to reproducibility challenges. Previously, our lab performed virtual microdissection on bulk RNA-seq patient samples establishing robust prognostic gene signatures describing an aggressive basal-like and drug-responsive classical tumor subtypes highlighting the importance of cancer heterogeneity across patients. Using these signatures as patient classifiers has been an important utility in preliminary clinical trials and therapeutic profiling of patient derived organoids. Building evidence suggests patient unique TME composition impacts PDAC progression and resistance to standard treatments. While patient tissue characterization with bulk measurements has provided key insights into cancer biology, parsing the complex tumor microenvironments requires higher resolution due to the widespread stromal involvement and sparse neoplastic populations. Single-cell sequencing delivers the analytical power to help identify variable TME elements between patients that lead to the distinct prognostic and therapeutic responses. Thus, understanding the extent and role of TME heterogeneity in PDAC across patient tumor subtypes is paramount to widen the door for personalized medicine in oncology. In this proposal, I will establish a comprehensive single-cell atlas of human PDAC TME to significantly lower the barrier between researchers and complex single-cell transcriptomics data to explore novel prognostic and synergistic therapeutic targets. I will use local and public single cell RNA-seq data of PDAC tissue to investigate the extent and role of cellular heterogeneity across patient tumor subtypes. Specifically, I will define molecular signatures and map out the interactome of functional cell types within stromal, lymphocytic, myeloid populations at unprecedented spatial resolution. Ultimately, by integrating high-dimensional data from single-cell RNA-seq and Spatial Transcriptomics, this work will shed light on the intricate tissue pathology while laying down a broad framework for understanding multi-axis cell interactions behind progression and resistance in diverse cancer types.


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 = $56,974 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	4	11/24/2023	NON-COMPETING CONTINUATION	$55,194
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	4	5/7/2024	NON-COMPETING CONTINUATION	$1,780
														Subtotal = $56,974

Issue Date FY: 2023 ( Subtotal = $52,694 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	3	5/22/2023	NON-COMPETING CONTINUATION	$942
2023	2023	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	3	11/29/2022	NON-COMPETING CONTINUATION	$51,752
														Subtotal = $52,694

Issue Date FY: 2022 ( Subtotal = $24,822 )
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	2	12/9/2021	NON-COMPETING CONTINUATION	$30,036
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	002	2	3/25/2022	NON-COMPETING CONTINUATION	$7,535
2022	2022	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	003	2	5/27/2022	NON-COMPETING CONTINUATION	$716
2022	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	1	1/4/2022	NEW	-$13,981
2022	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	004	1	6/25/2022	NEW	$516
														Subtotal = $24,822

Issue Date FY: 2021 ( Subtotal = $51,036 )
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	002	1	2/4/2021	NEW	$516
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	1	12/9/2020	NEW	$50,520
2021	2021	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	WEST 5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	1	12/9/2020	NEW	$0
														Subtotal = $51,036

Grand Total All Awards = $185,526

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Single Cell Deconvolution of the Pancreatic Tumor Microenvironment

Award Number: F30CA257489

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/09/2020

PERIOD OF PERFORMANCE END DATE: 12/08/2024

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