Friday, October 3, 2025 10/3/2025

Reproductive Hormones - Biological and Molecular Actions

Award Number: R01HD008188
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/1974
PERIOD OF PERFORMANCE END DATE: 03/31/2030

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Reproductive Hormones - Biological and Molecular Actions - PROJECT SUMMARY Advancing our mechanistic understanding of androgen-dependent male reproductive function requires an in- depth structural understanding of the core transcriptional complex in which ligand-occupied androgen receptor (AR) in complex with steroid receptor coactivator-2 (SRC-2) and p300 enacts transcriptional initiation of specific androgen-responsive gene expression programs. Until recently, structural information on the assembly modes by which the nuclear receptor (NR) engages with primary and secondary coregulators (Coregs) was limited to studies based on NR and Coreg protein fragments, which provided a significantly incomplete and, in many cases, an erroneous perspective of NR/Coreg transcriptional complex formation. To address this limitation, my team recently used cryogenic electron microscopy (cryo-EM) and proteomics to solve the quaternary structure of a number of NR/Coreg transcriptional complexes related to cancer biology at a full-length structural level. Apart from providing essential insights into the structure and assembly mechanisms of these core transcriptional complexes, an important “take away” from these investigations was that the structure and stoichiometry of the transcriptional complex for one NR cannot be extrapolated to explain the structure of another NR, despite sharing a similar functional domain organization. With this mind, Specific Aim 1 studies will use breakthrough advances in cryo-EM to obtain the quaternary structure of the DNA-bound liganded AR dimer in complex with SRC-2 and p300. Advancing the applicability of cryo-EM further, structural investigations in Specific Aim 1 will also solve the 3-dimensional structure of the core AR/Coreg transcriptional assembly in complex with the nucleosome core particle, the next level of structural complexity to be studied if we are to significantly advance our understanding of AR-mediated transcriptional initiation in the context of chromatin. Studies in Specific Aim 2 will apply cryo-EM to determine the structure of an AR(N727K) transactivation mutant as an approach to elucidate (at a full-length structural level) the importance of allostery within the AR dimeric complex in N- and C-terminal cooperativity, a prerequisite for Coreg recruitment and transcriptional activation. The structural studies in Specific Aims 1 and 2 will be functionally complemented in Specific Aim 3 by versatile cell-free assays of AR or AR(N727K)/Coreg-mediated in vitro transcription and enhancer-promoter crosstalk at an AR target gene at the proteome level. Providing in vivo support for findings from Specific Aims 1-3, a uniquely engineered AR point mutant mouse in Specific Aim 4 will be phenotyped at the histological, cellular and molecular level to define the importance of AR N/C terminal domain cooperativity in male reproduction, in particular spermatogenesis. Collectively, our studies will furnish a structural, functional and physiological basis for AR-mediated transcription in the maintenance of male reproductive function. In keeping with NICHD priority goals, outcomes from these studies will also provide a conceptual framework for understanding abnormal responses to androgen that lead to androgen insensitivity.


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 = $686,129 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	52	3/17/2025	COMPETING CONTINUATION	$686,129
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	004	52	6/23/2025	COMPETING CONTINUATION	$186,994
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	002	52	5/13/2025	COMPETING CONTINUATION	$0
2025	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	003	51	6/23/2025	NON-COMPETING CONTINUATION	-$186,994
2025	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	51	3/3/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $686,129

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	51	5/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $622,138 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	51	3/9/2023	NON-COMPETING CONTINUATION	$622,138
														Subtotal = $622,138

Issue Date FY: 2022 ( Subtotal = $1,022,138 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	50	6/9/2022	SUPPLEMENT FOR EXPANSION	$400,000
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	50	4/19/2022	NON-COMPETING CONTINUATION	$622,138
														Subtotal = $1,022,138

Issue Date FY: 2021 ( Subtotal = $622,138 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	49	3/11/2021	NON-COMPETING CONTINUATION	$622,138
														Subtotal = $622,138

Issue Date FY: 2020 ( Subtotal = $634,835 )
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	48	3/20/2020	NON-COMPETING CONTINUATION	$634,835
2020	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	47	2/20/2020	COMPETING CONTINUATION	$0
														Subtotal = $634,835

Issue Date FY: 2019 ( Subtotal = $634,835 )
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	47	8/6/2019	COMPETING CONTINUATION	$634,835
2019	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	46	7/26/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $634,835

Issue Date FY: 2018 ( Subtotal = $621,103 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	46	4/26/2018	NON-COMPETING CONTINUATION	$62,110
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	46	4/11/2018	NON-COMPETING CONTINUATION	$558,993
														Subtotal = $621,103

Issue Date FY: 2017 ( Subtotal = $621,103 )
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	45	6/2/2017	NON-COMPETING CONTINUATION	$621,103
														Subtotal = $621,103

Issue Date FY: 2016 ( Subtotal = $614,891 )
2016	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	44	3/23/2016	NON-COMPETING CONTINUATION	$614,891
														Subtotal = $614,891

Issue Date FY: 2015 ( Subtotal = $605,575 )
2015	2015	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	43	3/25/2015	NON-COMPETING CONTINUATION	$605,575
														Subtotal = $605,575

Issue Date FY: 2014 ( Subtotal = $621,103 )
2014	2014	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	42	5/26/2014	COMPETING CONTINUATION	$621,103
														Subtotal = $621,103

Issue Date FY: 2013 ( Subtotal = $583,565 )
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	41	5/29/2013	NON-COMPETING CONTINUATION	$30,134
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	41	2/27/2013	NON-COMPETING CONTINUATION	$553,431
														Subtotal = $583,565

Issue Date FY: 2012 ( Subtotal = $614,925 )
2012	2012	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	40	2/28/2012	NON-COMPETING CONTINUATION	$614,925
														Subtotal = $614,925

Issue Date FY: 2011 ( Subtotal = $624,290 )
2011	2011	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	39	7/1/2011	NON-COMPETING CONTINUATION	$56,754
2011	2011	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	39	2/18/2011	NON-COMPETING CONTINUATION	$567,536
														Subtotal = $624,290

Issue Date FY: 2010 ( Subtotal = $739,598 )
2010	2010	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	38	3/4/2010	NON-COMPETING CONTINUATION	$630,596
2010	2010	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Trans-NIH Recovery Act Research Support	001	38	8/4/2010	SUPPLEMENT FOR EXPANSION	$109,002
														Subtotal = $739,598

Issue Date FY: 2009 ( Subtotal = $622,508 )
2009	2009	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Population Research	001	37	3/24/2009	COMPETING CONTINUATION	$622,508
2009	2008	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	36	3/24/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $622,508

Issue Date FY: 2008 ( Subtotal = $648,775 )
2008	2008	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	36	5/26/2008	NON-COMPETING CONTINUATION	$648,775
														Subtotal = $648,775

Issue Date FY: 2007 ( Subtotal = $644,324 )
2007	2007	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	35	5/10/2007	NON-COMPETING CONTINUATION	$644,324
														Subtotal = $644,324

Grand Total All Awards = $16,486,705

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Reproductive Hormones - Biological and Molecular Actions

Award Number: R01HD008188

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/1974

PERIOD OF PERFORMANCE END DATE: 03/31/2030

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