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Regulation of Intracellular Signaling

Award Number: R35GM131768
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: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2029

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Regulation of Intracellular Signaling - Summary (30 lines) Our research program aims to understand how cells control intracellular signaling to respond and adapt to their environments. We will focus on three processes: Project 1 will examine the chemotactic migration of cells in extracellular chemical gradients, Project 2 will look at DNA repair after oxidative, genotoxic, and mechanical stress, and Project 3 will investigate the reprogramming of cell proliferation signaling in response to receptor tyrosine kinase inhibition. Project 1: GTPases are crucial for signal transduction in many cellular activities. Recently, we discovered an unforeseen, evolutionarily conserved mechanism by which GDP-bound Rho GTPase activates mTORC2, a critical serine/threonine kinase, in Dictyostelium and human cells. We will investigate the fundamental mechanism underlying this novel regulation of small GTPases using the robust chemotactic signaling in Dictyostelium cells as a discovery tool supported by an array of cutting-edge technologies. Successful outcomes will broadly impact tissue development, wound healing, neuronal wiring, and immune responses, as chemotaxis is crucial for these essential processes. Project 2: PTEN protects the genome from stress in the nucleus. PTEN accumulates in the nucleus upon stress via ubiquitin signaling. Identifying the ubiquitin ligase that controls PTEN after stress represents a critical knowledge gap in our understanding of PTEN's stress signaling. Using a genome-wide CRISPR screen, we will comprehensively test the function of E3 ligases under various forms of stress, such as oxidative, genotoxic, and mechanical stress. We will subsequently investigate how stress regulates the ubiquitin ligases. Project 3: Cells can adapt to unfavorable surroundings and weakened physiology by rearranging signal transduction pathways. We will analyze how cells alter signaling networks when the activity of vital signaling components is inhibited using innovative approaches, including AI-based multiplexed biosensor barcoding. We focus on the EGF receptor, which is essential for physiology and development. Outcomes will reveal the basic mechanisms by which cells can rewire signal transduction pathways and bypass the inhibition of essential signaling elements.


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 = $486,338 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	8	2/27/2026	NON-COMPETING CONTINUATION	$486,338
														Subtotal = $486,338

Issue Date FY: 2025 ( Subtotal = $486,338 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	002	7	2/26/2025	NON-COMPETING CONTINUATION	$437,704
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	003	7	8/14/2025	NON-COMPETING CONTINUATION	$48,634
2025	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	6	11/25/2024	COMPETING CONTINUATION	$0
2025	2023	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	5	2/18/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $486,338

Issue Date FY: 2024 ( Subtotal = $516,338 )
2024	2024	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	6	3/14/2024	COMPETING CONTINUATION	$516,338
														Subtotal = $516,338

Issue Date FY: 2023 ( Subtotal = $422,771 )
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	5	5/17/2023	SUPPLEMENT FOR EXPANSION	$13,396
2023	2023	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	5	3/3/2023	NON-COMPETING CONTINUATION	$409,375
														Subtotal = $422,771

Issue Date FY: 2022 ( Subtotal = $409,375 )
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	4	3/29/2022	NON-COMPETING CONTINUATION	$384,371
2022	2022	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	4	7/21/2022	NON-COMPETING CONTINUATION	$25,004
														Subtotal = $409,375

Issue Date FY: 2021 ( Subtotal = $535,534 )
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	3	7/20/2021	SUPPLEMENT FOR EXPANSION	$126,159
2021	2021	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	3	3/24/2021	NON-COMPETING CONTINUATION	$409,375
														Subtotal = $535,534

Issue Date FY: 2020 ( Subtotal = $460,119 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	001	2	9/15/2020	SUPPLEMENT FOR EXPANSION	$50,744
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	2	3/27/2020	NON-COMPETING CONTINUATION	$409,375
														Subtotal = $460,119

Issue Date FY: 2019 ( Subtotal = $432,594 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Biomedical Research and Research Training	000	1	5/24/2019	NEW	$432,594
														Subtotal = $432,594

Grand Total All Awards = $3,749,407

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Regulation of Intracellular Signaling

Award Number: R35GM131768

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: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2029

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