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Adhesive regulation during cell migration

Award Number: R01CA085862
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/10/2000
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Adhesive regulation during cell migration - ABSTRACT Cell migration is important in normal development, wound healing and cancer. The long-term goal of this work is to study cell migration in the context of cancer. The most motile, and understudied, population of cells in the tumor microenvironment (TME) are neutrophils, which are primary effector cells of the innate immune response. The presence of chronic neutrophil- mediated inflammation has been associated with the initiation and progression of cancer. However, the role of neutrophils in the tumor microenvironment remains controversial in part because neutrophils can play both pro- and anti-tumor roles. We aim to address this gap by increasing our understanding of how neutrophils are recruited and regulated by the tumor microenvironment during tumor progression. We will test the overall hypotheses that specific signaling pathways induced by transformed cells drive neutrophil recruitment, and that neutrophils “educated” in the tumor microenvironment alter tumor progression. To address these hypotheses, we have developed a robust toolbox using zebrafish to enable in situ imaging of the dynamic behavior of neutrophils, macrophages and cancer cells, in real time, in melanoma and liver cancer models. We take advantage of a new zebrafish model of fibrolamellar carcinoma (FLC), an aggressive early onset cancer that exhibits increased inflammation and early progression, similar to human disease. Here, we propose to examine the role of neutrophils in liver cancer and melanoma inflammation and progression (Aim 1). We will harness TRAPseq findings from neutrophils, macrophages and epithelial cells to probe the role of oncogene-induced genes on neutrophils in the tumor microenvironment and tumorigenesis, including the role of neutrophil intrinsic genes p47phox and the phosphatase ptprja on neutrophil polarization and tumor progression (Aim 2). Finally, we will examine neutrophil-macrophage cross talk in the tumor microenvironment and the role of macrophage polarization on neutrophil inflammation and tumor progression (Aim 3). While there has been substantial interest in manipulating the adaptive immune system to treat cancer, the therapeutic possibilities of the innate immune system remain under-studied. Understanding mechanisms that regulate neutrophils in the tumor microenvironment will enhance basic mechanistic knowledge regarding intercellular interactions, facilitate the design of new strategies to treat cancer and potentially improve the efficacy of cancer immunotherapy.


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 = $326,450 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	24	12/4/2024	NON-COMPETING CONTINUATION	$326,450
														Subtotal = $326,450

Issue Date FY: 2024 ( Subtotal = $344,586 )
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	001	23	4/23/2024	NON-COMPETING CONTINUATION	$18,136
2024	2024	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	23	11/14/2023	NON-COMPETING CONTINUATION	$326,450
														Subtotal = $344,586

Issue Date FY: 2023 ( Subtotal = $362,722 )
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	22	11/15/2022	NON-COMPETING CONTINUATION	$326,450
2023	2023	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	001	22	3/15/2023	NON-COMPETING CONTINUATION	$36,272
														Subtotal = $362,722

Issue Date FY: 2022 ( Subtotal = $362,722 )
2022	2022	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	21	12/21/2021	COMPETING CONTINUATION	$362,722
														Subtotal = $362,722

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	20	10/28/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $310,192 )
2019	2019	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	20	7/2/2019	NON-COMPETING CONTINUATION	$310,192
														Subtotal = $310,192

Issue Date FY: 2018 ( Subtotal = $319,787 )
2018	2018	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	19	6/11/2018	NON-COMPETING CONTINUATION	$319,787
														Subtotal = $319,787

Issue Date FY: 2017 ( Subtotal = $319,787 )
2017	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	18	6/20/2017	NON-COMPETING CONTINUATION	$319,787
														Subtotal = $319,787

Issue Date FY: 2016 ( Subtotal = $319,787 )
2016	2016	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	17	7/1/2016	NON-COMPETING CONTINUATION	$319,787
														Subtotal = $319,787

Issue Date FY: 2015 ( Subtotal = $319,787 )
2015	2015	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Biology Research	000	16	7/1/2015	COMPETING CONTINUATION	$319,787
2015	2014	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 NORTH PARK STREET	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	001	15	7/1/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $319,787

Issue Date FY: 2014 ( Subtotal = $269,909 )
2014	2014	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	001	15	6/3/2014	NON-COMPETING CONTINUATION	$19,477
2014	2014	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	15	3/3/2014	NON-COMPETING CONTINUATION	$250,432
														Subtotal = $269,909

Issue Date FY: 2013 ( Subtotal = $261,562 )
2013	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	14	2/1/2013	NON-COMPETING CONTINUATION	$125,215
2013	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	001	14	6/28/2013	NON-COMPETING CONTINUATION	$136,347
														Subtotal = $261,562

Issue Date FY: 2012 ( Subtotal = $278,257 )
2012	2012	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	13	3/16/2012	NON-COMPETING CONTINUATION	$278,257
														Subtotal = $278,257

Issue Date FY: 2011 ( Subtotal = $278,169 )
2011	2011	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	12	1/13/2011	NON-COMPETING CONTINUATION	$258,176
2011	2011	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	002	12	5/12/2011	NON-COMPETING CONTINUATION	$19,993
2011	2011	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 NORTH PARK STREET	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	001	12	2/10/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $278,169

Issue Date FY: 2010 ( Subtotal = $286,863 )
2010	2010	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	11	3/23/2010	COMPETING CONTINUATION	$286,863
														Subtotal = $286,863

Issue Date FY: 2009 ( Subtotal = $272,487 )
2009	2009	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	10	4/6/2009	NON-COMPETING CONTINUATION	$272,487
														Subtotal = $272,487

Issue Date FY: 2008 ( Subtotal = $272,687 )
2008	2008	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 NORTH PARK STREET	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	9	4/4/2008	NON-COMPETING CONTINUATION	$272,687
														Subtotal = $272,687

Issue Date FY: 2007 ( Subtotal = $272,882 )
2007	2007	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 NORTH PARK STREET	MADISON	WI	53715	DANE	USA	Cancer Cause and Prevention Research	000	8	4/1/2007	NON-COMPETING CONTINUATION	$272,882
														Subtotal = $272,882

Issue Date FY: 2006 ( Subtotal = $281,226 )
2006	2006	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	750 UNIVERSITY AVENUE	MADISON	WI	53706	DANE	USA	Cancer Cause and Prevention Research	000	7	5/18/2006	NON-COMPETING CONTINUATION	$281,226
														Subtotal = $281,226

Issue Date FY: 2005 ( Subtotal = $290,338 )
2005	2005	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	750 UNIVERSITY AVENUE	MADISON	WI	53706	DANE	USA	Cancer Cause and Prevention Research	000	6	5/27/2005	COMPETING CONTINUATION	$290,338
														Subtotal = $290,338

Issue Date FY: 2004 ( Subtotal = $194,400 )
2004	2004	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	750 UNIVERSITY AVENUE	MADISON	WI	53706	DANE	USA	Cancer Biology Research	000	5	5/17/2004	NON-COMPETING CONTINUATION	$194,400
														Subtotal = $194,400

Issue Date FY: 2003 ( Subtotal = $310,657 ) (Continued on the next page)
Grand Total All Awards = $6,946,771

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Adhesive regulation during cell migration

Award Number: R01CA085862

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/10/2000

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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