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Molecular probes to image and target the neurovascular unit in health and disease

Award Number: R01NS115544
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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Molecular probes to image and target the neurovascular unit in health and disease - ABSTRACT Endothelial cells (ECs), astrocytes and pericytes are integral components of the neurovascular unit (NVU) and play critical roles in blood brain barrier (BBB) formation and maintenance. These cells express uptake and efflux membrane transporters that regulate CNS penetration of molecules, therapeutic drugs and toxins. The function of the BBB and transporters is likely disrupted in many neurological disorders. Thus, development of tools to study NVU cells and their properties of BBB selective transport in vivo is a key priority in translational neuroscience research. We have discovered a unique set of small molecules that can be selectively transported into the cytoplasm of either ECs, pericytes or astrocytes with exquisite affinity and specificity. We have evidence that these molecules enter cells through membrane transporters, selectively expressed in each cell type. We hypothesize that these molecules could be adapted as probes for intravital animal and human imaging and also for cell-specific delivery of drugs. In this proposal, we aim to identify the precise mechanisms of probe membrane transport in vivo; establish the feasibility of using these molecules as cell-specific drug carriers or as radiopharmaceuticals for human imaging with positron emission tomography (PET) and finally test their in vivo properties in models of Alzheimer's disease and stroke. This project will improve our understanding of molecular transport mechanisms across the BBB and may transform the ability to selectively image and pharmacologically modulate cells of the NVU in health and disease.


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 = $606,191 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	7/3/2024	NON-COMPETING CONTINUATION	$0
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	11/24/2023	NON-COMPETING CONTINUATION	$545,573
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/10/2024	NON-COMPETING CONTINUATION	$60,618
														Subtotal = $606,191

Issue Date FY: 2023 ( Subtotal = $606,191 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/24/2022	NON-COMPETING CONTINUATION	$545,573
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	1/31/2023	NON-COMPETING CONTINUATION	$60,618
														Subtotal = $606,191

Issue Date FY: 2022 ( Subtotal = $646,664 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/4/2022	NON-COMPETING CONTINUATION	$545,573
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	3/28/2022	NON-COMPETING CONTINUATION	$60,618
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/11/2022	SUPPLEMENT FOR EXPANSION	$40,473
														Subtotal = $646,664

Issue Date FY: 2021 ( Subtotal = $646,663 )
2021	2021	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/11/2021	NON-COMPETING CONTINUATION	$60,619
2021	2021	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/4/2020	NON-COMPETING CONTINUATION	$545,572
2021	2021	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	6/7/2021	SUPPLEMENT FOR EXPANSION	$40,472
														Subtotal = $646,663

Issue Date FY: 2020 ( Subtotal = $606,191 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/15/2019	NEW	$500,110
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	1/3/2020	NEW	$106,081
														Subtotal = $606,191

Grand Total All Awards = $3,111,900

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Molecular probes to image and target the neurovascular unit in health and disease

Award Number: R01NS115544

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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