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Regulation of cell proliferation by CRL ubiquitin ligases

Award Number: R35GM136250
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: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Regulation of cell proliferation by CRL ubiquitin ligases - PROJECT ABSTRACT / SUMMARY Over four decades have elapsed since the discovery of the ubiquitin-proteasome system, yet our comprehension of its regulatory intricacies remains incomplete. This knowledge gap persists largely due to the limited characterization of the multitude of ubiquitin ligase enzymes, numbering approximately 600 in mammals. Within our laboratory, our primary focus has centered on unraveling the mechanisms through which Cullin-RING Ubiquitin Ligase (CRL) complexes orchestrate the three fundamental aspects of cellular life: growth, proliferation, and survival. Our contributions have been pivotal in elucidating the timing, spatial dynamics, and biological function of the CRL-mediated degradation of critical cellular regulators. Initially, our research endeavors were focused on delineating the temporal control of the mammalian cell cycle by the ubiquitin-proteasome system. Over time, our scope has broadened to encompass three distinct realms of investigation: cell signaling, cell cycle regulation, and the DNA damage response. This expansion has been facilitated by our discovery-oriented approach, which, in contrast to traditional hypothesis-driven methods, remains unbiased. Moreover, the results of these genetics and proteomics screens are not the end goal; they only set the stage for our mechanistic studies. This process often leads us to unexpected new territories, expanding our horizons to novel biological processes. Entering new research areas provides us with a broad vision that is less often attained within compartmentalized fields. Moreover, it enriches us by spurring new collaborations with other scientists and by prompting us to thoroughly learn new disciplines. The cross- pollination of diverse fields and ideas is one of the foundations of our modus operandi. In summary, we adopt a holistic and interdisciplinary approach to provide transformative insights into fundamental biological processes, particularly those governed by CRLs. The current proposed research endeavors will cover all the mechanistic studies conducted within our laboratory across the three aforementioned areas. Specifically, we intend to leverage our established expertise in the ubiquitin field to unearth the molecular mechanisms dictating CRL- mediated control over signal transduction pathways, cell cycle progression, and DNA repair. Furthermore, through a blend of biochemical and in vivo analyses, we aim to shed light on the regulatory mechanisms underlying general cellular homeostasis. Collectively, our expertise in the field of CRLs-mediated degradation, our validated methods for its investigation, our unique collection of reagents and tools, and the rigor of our prior research strongly ensure that our studies will continue to uncover novel CRL networks relevant to essential cellular processes, potentially unveiling novel insights into disease mechanisms.


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 = $389,850 )
2026	2026	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	7	4/3/2026	NON-COMPETING CONTINUATION	$389,850
														Subtotal = $389,850

Issue Date FY: 2025 ( Subtotal = $389,850 )
2025	2025	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	6	5/13/2025	COMPETING CONTINUATION	$389,850
2025	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	5	11/5/2024	NON-COMPETING CONTINUATION	$0
2025	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	002	5	7/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $389,850

Issue Date FY: 2024 ( Subtotal = $379,792 )
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	002	5	3/27/2024	SUPPLEMENT FOR EXPANSION	$40,792
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	003	5	6/21/2024	NON-COMPETING CONTINUATION	$33,899
2024	2024	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	5	3/22/2024	NON-COMPETING CONTINUATION	$305,101
2024	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	4	1/30/2024	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $379,792

Issue Date FY: 2023 ( Subtotal = $436,902 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	4	3/21/2023	NON-COMPETING CONTINUATION	$339,000
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	4	4/7/2023	SUPPLEMENT FOR EXPANSION	$97,902
														Subtotal = $436,902

Issue Date FY: 2022 ( Subtotal = $396,110 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	002	3	7/11/2022	SUPPLEMENT FOR EXPANSION	$57,110
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	001	3	6/23/2022	NON-COMPETING CONTINUATION	$33,903
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	3	3/11/2022	NON-COMPETING CONTINUATION	$305,097
														Subtotal = $396,110

Issue Date FY: 2021 ( Subtotal = $339,000 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	2	3/26/2021	NON-COMPETING CONTINUATION	$339,000
														Subtotal = $339,000

Issue Date FY: 2020 ( Subtotal = $339,000 )
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Biomedical Research and Research Training	000	1	4/23/2020	NEW	$339,000
														Subtotal = $339,000

Grand Total All Awards = $2,670,504

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Regulation of cell proliferation by CRL ubiquitin ligases

Award Number: R35GM136250

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: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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