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A scalable optogenetic system of focal stroke induction in zebrafish for testing stroke disparity genes

Award Number: SC3GM132058
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Stroke is one of the leading causes of death in the U.S. and also a leading cause of adult disability with severe societal burdens. Ischemic strokes, caused by the thromboembolic occlusion of cerebral arteries, constitute the majority of stroke incidences and the rest are hemorrhagic strokes with ruptured blood vessels. In the U.S., stroke incidence shows clear disparity between African Americans and Caucasians with much higher frequency (~240%) in blacks. Despite intensive search for treatment, recombinant tissue plasminogen activator (rtPA) remains the only FDA-approved post-stroke medicine with limited effectiveness. Behind this woefully inadequate dearth of stroke therapeutics lies the difficulties in generating a sufficiently large number of stroke-induced animals for effective drug screening, as a highly labor-intensive surgical procedure (middle cerebral artery occlusion) is still the method of choice to induce ischemic strokes in model animals. Photothrombosis is one of rapidly adopted new methods to induce ischemic strokes in rodents, with a number of advantages such as highly reproducible infarct size and location with minimal mortality. In this procedure, focal illumination of defined wavelength light on the exposed skull activates an IV-injected photosensitive chemical (eg. Rose-Bengal) in the bloodstream, causing injuries in endothelial cells and local platelet aggregation, leading to the clogging of the affected blood vessel. However, even in this case labor-intensive procedures that cannot not easily be scaled up must be utilized to create the stroke model. Recently, photothrombic ischemic stroke has also been successfully induced in the adult zebrafish brain by focal illumination following a manual injection of Rose-Bengal, thus providing an additional vertebrate animal model system for stroke research. In this regard, an exciting novel genetic approach, which eliminates the manual injection of photosensitive chemicals, was recently created and tested successfully to selectively induce apoptotic cell death by light illumination in the adult zebrafish heart. Here we propose a creation of a readily scalable, optogenetically induced stroke system using transgenic zebrafish, development of a behavioral test system to identify novel therapeutic chemicals, and to test GWAS (genome wide association study)-identified stroke risk variants of the human APOL1 gene, also known as prominent kidney disorder risk factors in people of African ancestry.


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	2022	NORTH CAROLINA CENTRAL UNIVERSITY	1801 FAYETTEVILLE ST	DURHAM	NC	27707	DURHAM	USA	Biomedical Research and Research Training	000	4	8/26/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $111,000 )
2022	2022	NORTH CAROLINA CENTRAL UNIVERSITY	1801 FAYETTEVILLE ST	DURHAM	NC	27707	DURHAM	USA	Biomedical Research and Research Training	000	4	2/9/2022	NON-COMPETING CONTINUATION	$99,900
2022	2022	NORTH CAROLINA CENTRAL UNIVERSITY	1801 FAYETTEVILLE ST	DURHAM	NC	27707	DURHAM	USA	Biomedical Research and Research Training	001	4	6/20/2022	NON-COMPETING CONTINUATION	$11,100
														Subtotal = $111,000

Issue Date FY: 2021 ( Subtotal = $111,000 )
2021	2021	NORTH CAROLINA CENTRAL UNIVERSITY	1801 FAYETTEVILLE ST	DURHAM	NC	27707	DURHAM	USA	Biomedical Research and Research Training	000	3	2/25/2021	NON-COMPETING CONTINUATION	$111,000
														Subtotal = $111,000

Issue Date FY: 2020 ( Subtotal = $111,000 )
2020	2020	NORTH CAROLINA CENTRAL UNIVERSITY	1801 FAYETTEVILLE ST	DURHAM	NC	27707	DURHAM	USA	Biomedical Research and Research Training	000	2	2/11/2020	NON-COMPETING CONTINUATION	$111,000
														Subtotal = $111,000

Issue Date FY: 2019 ( Subtotal = $111,000 )
2019	2019	NORTH CAROLINA CENTRAL UNIVERSITY	1801 FAYETTEVILLE ST	DURHAM	NC	27707	DURHAM	USA	Biomedical Research and Research Training	000	1	3/7/2019	NEW	$111,000
														Subtotal = $111,000

Grand Total All Awards = $444,000

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A scalable optogenetic system of focal stroke induction in zebrafish for testing stroke disparity genes

Award Number: SC3GM132058

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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