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Epigenetic Mechanisms of Developmental Regulation of Fetal, Newborn, and Adult Cerebral Artery Sympathetic Innervation and Alpha1 Adrenergic Receptor Subtypes

Award Number: R01HL135786
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Title: Epigenetic Mechanisms of Developmental Regulation of Fetal, Newborn, and Adult Cerebral Artery Sympathetic Innervation and Alpha1 Adrenergic Receptor Subtypes Project Summary: During the past half century there has been the rising rate of preterm birth combined with a lowering of the age limit of viability. The premature fetus is more prone to germinal matrix and other intracerebral hemorrhage, intraventricular hemorrhage, and related problems as a consequence of stress during the process of birth. In contrast, the term-fetus is able to autoregulate cerebral blood ¿ow (CBF) despite the increase in systemic pressure and minimize the occurrence of stress-induced hemorrhages. Recently, we have demonstrated that lack of cerebral blood ¿ow (CBF) autoregulation in the premature fetus is associated with immaturity of the sympathetic (adrenergic) system. In concert with this, we also have demonstrated that the adrenergic system undergoes a signi¿cant maturation with development. In the proposed studies, we attempt to determine the mechanisms by which the premature fetus can have greater cerebral autoregulation capability, as observed in the newborn lamb. In the ¿rst three speci¿c aims, ex-vivo, we will examine the role of DNA methylation, histone modi¿cations, microRNA, and lncRNA on the expression of the three alpha 1 adrenergic receptor subtypes in premature fetus, near-term fetus, newborn lamb, and adult sheep. In the fourth speci¿c aim, in vivo, in the chronically catheterized preterm fetus, near-term fetus, newborn lamb, and adult sheep, we will determine the effect of DNA methylation, histone modi¿cations, microRNAs, lncRNA, and alpha 1-adrenergic receptor subtypes in CBF regulation with development in both the sexes. Overall, these studies will provide vital insights in the sympathetic regulation of CBF with development, and suggest approaches to prevent or ameliorate CBF dysregulation.


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: 2024 ( Subtotal = $0 )
2024	2021	LOMA LINDA UNIVERSITY	11145 ANDERSON ST	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	000	47	10/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $395,000 )
2021	2021	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	001	47	5/15/2021	NON-COMPETING CONTINUATION	$39,500
2021	2021	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	000	47	11/24/2020	NON-COMPETING CONTINUATION	$355,500
														Subtotal = $395,000

Issue Date FY: 2020 ( Subtotal = $395,000 )
2020	2020	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	000	46	12/24/2019	NON-COMPETING CONTINUATION	$375,250
2020	2020	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	001	46	1/25/2020	NON-COMPETING CONTINUATION	$19,750
														Subtotal = $395,000

Issue Date FY: 2019 ( Subtotal = $395,000 )
2019	2019	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	000	45	1/18/2019	NON-COMPETING CONTINUATION	$395,000
														Subtotal = $395,000

Issue Date FY: 2018 ( Subtotal = $395,000 )
2018	2018	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	000	44	12/10/2017	NON-COMPETING CONTINUATION	$387,100
2018	2018	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	001	44	6/22/2018	NON-COMPETING CONTINUATION	$7,900
														Subtotal = $395,000

Issue Date FY: 2017 ( Subtotal = $395,000 )
2017	2017	LOMA LINDA UNIVERSITY	11060 ANDERSON ST BLDG MAGAN HALL	LOMA LINDA	CA	92350	SAN BERNARDINO	USA	Cardiovascular Diseases Research	000	43	12/9/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$395,000
														Subtotal = $395,000

Grand Total All Awards = $1,975,000

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Epigenetic Mechanisms of Developmental Regulation of Fetal, Newborn, and Adult Cerebral Artery Sympathetic Innervation and Alpha1 Adrenergic Receptor Subtypes

Award Number: R01HL135786

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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