Wednesday, August 6, 2025 8/6/2025

Sex Hormone Receptor Component And The Cell Genome

Award Number: R01HD007857
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: 05/01/1977
PERIOD OF PERFORMANCE END DATE: 02/29/2028

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View Award Description

Sex Hormone Receptor Component And The Cell Genome - Project/Summary Abstract Significant advances in our mechanistic understanding of progesterone receptor (PR) mediated transcription are inextricably tied to our structural knowledge of the core transcriptional complex through which PR along with its coregulators (Coregs) control target gene transcription. Pioneering the use of single-particle cryo- electron microscopy (cryo-EM) in steroid hormone nuclear receptor (NR) biology, we recently revealed the quaternary structure of the transcriptional complexes for the estrogen receptor (ERa) and androgen receptor (AR), which along with PR comprise the “NR triad” of sex steroid hormones that govern mammalian reproductive biology. Unlike ERa and AR, PR is composed of the PR-A and PR-B isoforms that mediate both distinct and overlapping progesterone transcriptional responses in physiological and pathophysiological contexts. Accordingly, a comprehensive understanding of the transcriptional response to progesterone can only occur through a structural characterization of the core transcriptional complexes of the homodimer and heterodimer configurations of these PR isoforms. Therefore, Aim 1 will use cryo-EM and complementary structural proteomic approaches to solve the quaternary structure of the core Coreg/transcriptional complex for the PR-A homodimer bound to DNA. Significantly, we have determined the core Coreg/transcriptional complex for the PR-B homodimer. Not only has this structural information provided critical insights into the unique assembly mechanisms by which PR-B recruits primary and secondary Coregs during transcriptional complex formation but reconfirms our ability to successfully execute the structural studies in Aims 1 and 2. Importantly, this technology presents a unique opportunity to investigate the contribution of the intrinsic disordered region of the activation function 1 (AF1) in PR during Coreg/transcriptional complex assembly. Despite its importance in PR mediated transactivation and its potential for therapeutic targeting, the AF1 domain (unlike the ordered AF2) is understudied due to its disordered topology. Using a PR AF1 mutant, Aim 2 will use cryo-EM and allied structural methods to assess the contribution of AF1’s structural disorder in the dynamic assembly mechanisms that underpin Coreg recruitment by PR-B to the nucleating transcriptional complex. This aim will be complemented by Aims 3 and 4, which will determine the transcriptional functional role of PR’s AF1 disordered structure using innovative cell-free/cell-based investigations and a CRISPR- engineered mouse model respectively. Collectively, these transformative investigations will: (i) furnish a much needed structural and mechanistic framework to explain the PR isoform-specific functional differences in physiological and pathophysiological contexts; (ii) define the structure-function relationship of AF1’s flexibility in dynamic interactions with multiple Coregs at the cell- and whole organism-level; and (iii) offer new opportunities to modulate PR isoform activity to clinically treat a spectrum of progesterone-dependent gynecologic disorders.


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 = $670,709 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	53	4/14/2025	NON-COMPETING CONTINUATION	$67,072
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	53	2/12/2025	NON-COMPETING CONTINUATION	$603,637
														Subtotal = $670,709

Issue Date FY: 2024 ( Subtotal = $664,002 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	52	5/2/2024	NON-COMPETING CONTINUATION	$60,365
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	52	2/13/2024	NON-COMPETING CONTINUATION	$603,637
														Subtotal = $664,002

Issue Date FY: 2023 ( Subtotal = $670,709 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	51	4/27/2023	COMPETING CONTINUATION	$670,709
2023	2021	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	50	12/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $670,709

Issue Date FY: 2021 ( Subtotal = $637,549 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	50	2/12/2021	NON-COMPETING CONTINUATION	$637,549
														Subtotal = $637,549

Issue Date FY: 2020 ( Subtotal = $650,560 )
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	49	2/20/2020	NON-COMPETING CONTINUATION	$650,560
														Subtotal = $650,560

Issue Date FY: 2019 ( Subtotal = $650,122 )
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	48	3/4/2019	NON-COMPETING CONTINUATION	$650,560
2019	2015	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	44	9/24/2019	NON-COMPETING CONTINUATION	-$438
														Subtotal = $650,122

Issue Date FY: 2018 ( Subtotal = $650,560 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	47	3/1/2018	NON-COMPETING CONTINUATION	$585,505
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	47	4/26/2018	NON-COMPETING CONTINUATION	$65,055
														Subtotal = $650,560

Issue Date FY: 2017 ( Subtotal = $650,560 )
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	46	3/9/2017	COMPETING CONTINUATION	$650,560
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	004	46	8/8/2017	COMPETING CONTINUATION	-$94
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	002	46	6/14/2017	COMPETING CONTINUATION	$2,927
2017	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	003	45	8/8/2017	EXTENSION WITH OR WITHOUT FUNDS	$94
2017	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	45	6/14/2017	EXTENSION WITH OR WITHOUT FUNDS	-$2,927
														Subtotal = $650,560

Issue Date FY: 2016 ( Subtotal = $496,937 )
2016	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	45	1/27/2016	EXTENSION WITH OR WITHOUT FUNDS	$496,937
														Subtotal = $496,937

Issue Date FY: 2015 ( Subtotal = $489,408 )
2015	2015	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	44	3/3/2015	NON-COMPETING CONTINUATION	$489,408
														Subtotal = $489,408

Issue Date FY: 2014 ( Subtotal = $487,903 )
2014	2014	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	43	3/6/2014	NON-COMPETING CONTINUATION	$487,903
														Subtotal = $487,903

Issue Date FY: 2013 ( Subtotal = $476,356 )
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	42	5/29/2013	NON-COMPETING CONTINUATION	$24,595
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	42	2/27/2013	NON-COMPETING CONTINUATION	$451,761
														Subtotal = $476,356

Issue Date FY: 2012 ( Subtotal = $505,873 )
2012	2012	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	41	3/23/2012	COMPETING CONTINUATION	$501,957
2012	2012	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	002	41	8/24/2012	SUPPLEMENT FOR EXPANSION	$3,916
2012	2011	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	40	3/15/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $505,873

Issue Date FY: 2011 ( Subtotal = $449,264 )
2011	2011	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	40	5/26/2011	NON-COMPETING CONTINUATION	$449,264
														Subtotal = $449,264

Issue Date FY: 2010 ( Subtotal = $465,223 )
2010	2010	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	39	5/4/2010	NON-COMPETING CONTINUATION	$465,223
														Subtotal = $465,223

Issue Date FY: 2009 ( Subtotal = $469,922 )
2009	2009	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Population Research	000	38	5/18/2009	NON-COMPETING CONTINUATION	$469,922
														Subtotal = $469,922

Issue Date FY: 2008 ( Subtotal = $469,922 )
2008	2008	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Population Research	000	37	4/18/2008	NON-COMPETING CONTINUATION	$469,922
														Subtotal = $469,922

Issue Date FY: 2007 ( Subtotal = $479,513 )
2007	2007	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Population Research	000	36	5/23/2007	COMPETING CONTINUATION	$479,513
														Subtotal = $479,513

Issue Date FY: 2006 ( Subtotal = $678,328 ) (Continued on the next page)
2006	2006	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	35	4/10/2006	NON-COMPETING CONTINUATION	$603,719
Grand Total All Awards = $14,735,260

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Sex Hormone Receptor Component And The Cell Genome

Award Number: R01HD007857

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: 05/01/1977

PERIOD OF PERFORMANCE END DATE: 02/29/2028

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