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Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.

Award Number: K23HL155898
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/17/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2026

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Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome. - ABSTRACT: Dr. Jonathan Santoro is a clinician-scientist focused on exploring the interface between vascular disease, cerebrovascular disease (CeVD) and inflammation in persons with Down syndrome (DS). This five-year mentored career development award will provide him with advanced training and skills in population-based data analysis, biostatistics, neuroimaging, and clinical trials development to ensure a successful transition to an independent research career. The outlined proposal builds on previously published work by Dr. Santoro and leverages a mentorship team of experts in DS, neurodevelopment, vascular disease, and cerebrovascular- inflammatory disorders in persons with DS at his home institution and other large academic DS centers. Research Context: Persons with DS have an increased risk of early CeVD, specifically moyamoya syndrome, and the initial presentation is often irreversible neurologic insult secondary to cerebrovascular accident. For persons with DS, there exists no validated means of assessing risk for CeVD. This K23 career development builds on previous work by Dr. Santoro who identified non-invasive ways to screen for CeVD in children with DS. This study will prospectively asses blood pressure (BP) in persons with DS and subsequently use this to predict pre-symptomatic CeVD (Aim 1). Next, this study will compare gold standard CeVD neuroimaging studies to various non-invasive, low-cost, biometric tools such as repeated BP measurements, transcranial Doppler ultrasound and neurocognitive testing to assess internal and predictive validity of these measures in the prediction of CeVD (Aim 2). As persons with DS are established to have immune dysregulation and systemic inflammatory profiles, we will also explore the role of systemic and vascular inflammatory biomarkers in the development of CeVD with the goal of identifying contributory inflammatory cascades that could be targeted with therapeutic interventions geared towards preventing CeVD in subsequent studies (Aim 3). Career Development Plan: Dr. Santoro will complete coursework in healthcare and science communication, data analysis, epidemiology, clinical trial design and biomedical informatics. This plan also will strengthen his competence in both bioinformatics and neuroimaging and be supplemented by institutional workshops and seminars. This experiential learning is designed to promote knowledge and skillset development needed to both execute his research and ensure that skills are developed for his transition to an independent researcher. Dr. Santoro’s career development goals will be supported through close mentorship by an experienced and committed interdisciplinary team and a combination of didactic, experiential, and team-based learning. This proposal and subsequent R01 proposals seek to improve the neurologic care of young persons with DS.


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 = $258,285 )
2025	2025	CHILDREN'S HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	000	5	12/24/2024	NON-COMPETING CONTINUATION	$258,285
														Subtotal = $258,285

Issue Date FY: 2024 ( Subtotal = $315,188 )
2024	2024	CHILDREN'S HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	000	4	3/12/2024	NON-COMPETING CONTINUATION	$192,671
2024	2024	CHILDREN'S HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	001	4	3/15/2024	SUPPLEMENT FOR EXPANSION	$62,517
2024	2024	CHILDREN'S HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	002	4	6/14/2024	SUPPLEMENT FOR EXPANSION	$60,000
														Subtotal = $315,188

Issue Date FY: 2023 ( Subtotal = $255,258 )
2023	2023	CHILDRENS HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	000	3	1/16/2023	NON-COMPETING CONTINUATION	$192,741
2023	2023	CHILDRENS HOSPITAL LOS ANGELES	4650 W SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	001	3	8/21/2023	SUPPLEMENT FOR EXPANSION	$62,517
														Subtotal = $255,258

Issue Date FY: 2022 ( Subtotal = $185,276 )
2022	2022	CHILDRENS HOSPITAL LOS ANGELES	4650 SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	000	2	2/28/2022	NON-COMPETING CONTINUATION	$185,276
														Subtotal = $185,276

Issue Date FY: 2021 ( Subtotal = $193,559 )
2021	2021	CHILDRENS HOSPITAL LOS ANGELES	4650 SUNSET BLVD	LOS ANGELES	CA	90027	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	2/16/2021	NEW	$193,559
														Subtotal = $193,559

Grand Total All Awards = $1,207,566

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Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.

Award Number: K23HL155898

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/17/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2026

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