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Slit2-ROBO signaling in pericytes and myeloid cells controls vascular development and ocular neovascular disease

Award Number: R01HL125811
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Slit2-ROBO signaling in pericytes and myeloid cells controls vascular development and ocular neovascular disease - PROJECT SUMMARY Pericytes and myeloid cells cooperate with endothelium to orchestrate formation of a properly branched, functional vessel network that sustains retinal function and thereby enables vision. Disrupted communication between endothelium, pericytes and myeloid cells leads to excessive and pathological angiogenesis in ocular neovascular diseases (ONDs) such as advanced age-related macular degeneration and diabetic retinopathy that cause vision loss in millions of Americans. Excessive angiogenesis is currently treated by inhibition of a single factor VEGF that targets endothelial cells only. In this proposal we identify a novel SLIT2-ROBO1&2 ligand- receptor pathway that promotes retinal neovascularization through direct receptor signaling effects in pericytes and myeloid cells. By targeting pericytes and myeloid cells, ROBO inhibition in ONDs may confer additional benefit over VEGF inhibition of ECs alone. We will define the molecular basis of SLIT2-ROBO1&2 signaling and its biological role in pericytes and myeloid cells to uncover novel biology controlling retinal development and homeostasis that could be applied to OND prevention.


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 = $548,496 )
2025	2025	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	8	3/7/2025	NON-COMPETING CONTINUATION	$548,496
														Subtotal = $548,496

Issue Date FY: 2024 ( Subtotal = $589,042 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	001	7	6/22/2024	NON-COMPETING CONTINUATION	$48,084
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	7	1/3/2024	NON-COMPETING CONTINUATION	$540,958
														Subtotal = $589,042

Issue Date FY: 2023 ( Subtotal = $601,064 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	6	3/13/2023	NON-COMPETING CONTINUATION	$601,064
														Subtotal = $601,064

Issue Date FY: 2022 ( Subtotal = $601,064 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	5	2/7/2022	COMPETING CONTINUATION	$601,064
														Subtotal = $601,064

Issue Date FY: 2019 ( Subtotal = -$237 )
2019	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	4	8/29/2019	NON-COMPETING CONTINUATION	-$237
														Subtotal = -$237

Issue Date FY: 2018 ( Subtotal = $416,250 )
2018	2018	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	4	4/27/2018	NON-COMPETING CONTINUATION	$416,250
														Subtotal = $416,250

Issue Date FY: 2017 ( Subtotal = $416,250 )
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	3	4/25/2017	NON-COMPETING CONTINUATION	$416,250
														Subtotal = $416,250

Issue Date FY: 2016 ( Subtotal = $416,250 )
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	2	4/11/2016	NON-COMPETING CONTINUATION	$416,250
														Subtotal = $416,250

Issue Date FY: 2015 ( Subtotal = $416,250 )
2015	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	SOUTH CENTRAL CT	USA	Cardiovascular Diseases Research	000	1	6/26/2015	NEW	$416,250
														Subtotal = $416,250

Grand Total All Awards = $4,004,429

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Slit2-ROBO signaling in pericytes and myeloid cells controls vascular development and ocular neovascular disease

Award Number: R01HL125811

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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