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Molecular Mechanisms Underlying Adaptor-Mediated Integrin Signaling in a Species-Specific Manner

Award Number: R35GM119560
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Molecular Mechanisms Underlying Adaptor-Mediated Integrin Signaling in a Species-Specific Manner - PROJECT SUMMARY/ABSTRACT My laboratory is interested in understanding the molecular mechanisms underlying cell adhesion and motility mediated by integrins and related small GTPases, and applying these findings to the development of new class of inhibitors for potential therapeutic benefits. Integrins are cell adhesion molecules that transduce signals across the plasma membrane in both directions. Thrombotic disorders, cardiovascular diseases, T cell proliferation defects, and many autoimmune diseases have been linked to the misregulation of integrin expression and its activity. The major gaps in the field of integrin and related signaling pathways include inaccurate molecular models of signaling events mediated by the integrin activator, a lack of understanding to the regulation of different integrin species, unknown mechanism underlying the peculiar dual GTPase specificity of their effector protein, and a lack of inhibitors targeting intracellular adaptors. We have obtained substantial preliminary data to bridge this gaps. The main goals of the lab for the next five years are to investigate the signaling mechanisms of the adaptors and integrins, focusing on the connection of isoforms and posttranslational modifications with specific integrin species and related GTPases, and to develop a new class of adaptor protein inhibitors to control integrin functions. The proposed studies include both basic research and translational research, which reflect an ever-expanding scope of the research in our research program. Our vigorous efforts would undoubtedly support us to achieve the overall goal of conquering integrin related diseases by more effective therapeutic interventions.


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 = $481,525 )
2025	2025	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	002	9	8/12/2025	NON-COMPETING CONTINUATION	$48,152
2025	2025	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	001	9	12/10/2024	NON-COMPETING CONTINUATION	$433,373
2025	2024	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	8	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $481,525

Issue Date FY: 2024 ( Subtotal = $481,525 )
2024	2024	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	8	11/20/2023	NON-COMPETING CONTINUATION	$433,373
2024	2024	THE INSTITUTE FOR CANCER RESEARCH	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	001	8	6/26/2024	NON-COMPETING CONTINUATION	$48,152
														Subtotal = $481,525

Issue Date FY: 2023 ( Subtotal = $548,229 )
2023	2023	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	001	7	3/29/2023	NON-COMPETING CONTINUATION	$48,152
2023	2023	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	7	1/4/2023	NON-COMPETING CONTINUATION	$433,373
2023	2023	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	002	7	8/16/2023	SUPPLEMENT FOR EXPANSION	$66,704
														Subtotal = $548,229

Issue Date FY: 2022 ( Subtotal = $550,879 )
2022	2022	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	001	6	12/13/2021	COMPETING CONTINUATION	$481,525
2022	2022	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	002	6	7/15/2022	SUPPLEMENT FOR EXPANSION	$69,354
2022	2020	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	5	12/3/2021	NON-COMPETING CONTINUATION	$0
2022	2020	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	003	5	7/28/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $550,879

Issue Date FY: 2020 ( Subtotal = $506,687 )
2020	2020	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	001	5	9/2/2020	NON-COMPETING CONTINUATION	$467,500
2020	2020	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	4	8/10/2020	SUPPLEMENT FOR EXPANSION	$39,187
														Subtotal = $506,687

Issue Date FY: 2019 ( Subtotal = $457,500 )
2019	2019	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	4	7/25/2019	NON-COMPETING CONTINUATION	$457,500
														Subtotal = $457,500

Issue Date FY: 2018 ( Subtotal = $568,972 )
2018	2018	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	001	3	9/20/2018	SUPPLEMENT FOR EXPANSION	$111,472
2018	2018	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	3	8/30/2018	NON-COMPETING CONTINUATION	$457,500
														Subtotal = $568,972

Issue Date FY: 2017 ( Subtotal = $457,500 )
2017	2017	INSTITUTE FOR CANCER RESEARCH, THE	333 COTTMAN AVE	PHILADELPHIA	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	2	9/1/2017	NON-COMPETING CONTINUATION	$457,500
														Subtotal = $457,500

Issue Date FY: 2016 ( Subtotal = $446,250 )
2016	2016	INSTITUTE FOR CANCER RESEARCH	333 Cottman Ave	Philadelphia	PA	19111	PHILADELPHIA	USA	Biomedical Research and Research Training	000	1	8/25/2016	NEW	$446,250
														Subtotal = $446,250

Grand Total All Awards = $4,499,067

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Molecular Mechanisms Underlying Adaptor-Mediated Integrin Signaling in a Species-Specific Manner

Award Number: R35GM119560

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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