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A New Phase in ABI1 Biology: AR We Abl to Characterize the Intractable AR-DNA-ABI1 Axis?

Award Number: F31CA291028
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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A New Phase in ABI1 Biology: AR We Abl to Characterize the Intractable AR-DNA-ABI1 Axis? - PROJECT SUMMARY/ABSTRACT Intrinsically disordered proteins (IDPs) are a class of proteins that do not have a fixed three-dimensional structure. IDPs can be fully unstructured, or contain modular regions of folded structure and unstructure, known as intrinsically disordered regions (IDRs). IDPs/IDRs are dynamic; fluctuating through diverse conformational ensembles that allow them to play widespread roles in biological functions, both during normal and pathological conditions. IDPs/IDRs play a pivotal role in a multitude of cellular processes including, but not limited to, proliferation, migration, differentiation, and apoptosis. Here, I will focus on Abl kinase Interactor 1 (ABI1), a modular scaffolding protein, whose biophysical investigation had remain elusive for decades. ABI1 is a multi-isoform and modular adaptor and scaffolding protein that plays a critical role in the organization of the cytoskeleton via downstream coordination of actin cytoskeletal reorganization with growth and proliferation signals as member of the WAVE complex. ABI1 also controls the progression of prostate tumors and acts as a prostate tumor suppressor wherein loss of ABI1 contributes to tumor metastasis. It is now known that ABI1 also functions in the nucleus, binding to DNA and nuclear hormone receptors (NHRs) like the androgen receptor (AR). My overall goal is to investigate the molecular basis of ABI1’s nuclear functions. In Aim 1, I will elucidate the mechanism of interaction between ABI1 and AR. Through biophysical methods, I will study the interaction of full-length ABI1 and full-length AR. Through truncation analysis, I will also determine the contribution of the folded domain(s) and IDR(s) from each protein towards binding and LLPS. In Aim 2, I will determine how ABI1 binds DNA and I will determine how ABI’s interactions with AR reciprocally affects each protein DNA binding properties. In this proposal, I will use an array of highly sensitive complementary biophysical techniques to determine the DNA binding properties of ABI1 in the presence and absence of full-length and various constructs of apo AR and AR bound to DNA. Due to their difficulty in expression and purification, there is little in vitro data on the biophysical and structural mechanisms underlying the interaction between ABI1 and AR. The results obtained will elucidate how the DNA-ABI1-AR axis regulates transcription, and will set the stage for developing novel inhibitors for prostate cancer. Without this knowledge, our understanding of ABI1’s functions in regulating AR in normal and prostate cancer will remain limited. This work will have a positive impact by providing a model for determining the mechanism of the interactions of ABI1 and other nuclear hormone receptors, such as the estrogen receptor, a major driver of breast cancer.


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 = -$40,694 )
2026	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Cancer Research Manpower	000	2	1/30/2026	NON-COMPETING CONTINUATION	-$40,324
2026	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Cancer Research Manpower	001	1	3/24/2026	NEW	-$370
														Subtotal = -$40,694

Issue Date FY: 2025 ( Subtotal = $40,324 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Cancer Research Manpower	000	2	8/1/2025	NON-COMPETING CONTINUATION	$40,324
														Subtotal = $40,324

Issue Date FY: 2024 ( Subtotal = $39,760 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Cancer Research Manpower	001	1	4/2/2024	NEW	$0
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Cancer Research Manpower	002	1	5/7/2024	NEW	$1,280
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Cancer Research Manpower	000	1	4/2/2024	NEW	$38,480
														Subtotal = $39,760

Grand Total All Awards = $39,390

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A New Phase in ABI1 Biology: AR We Abl to Characterize the Intractable AR-DNA-ABI1 Axis?

Award Number: F31CA291028

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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