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Endothelial and mural cell interaction in capillary malformation

Award Number: F32HL172637
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/02/2023
PERIOD OF PERFORMANCE END DATE: 01/01/2025

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Endothelial and mural cell interaction in capillary malformation - Project Summary/Abstract: Capillary Malformation (CM) is one of the most common vascular malformations. CM comprises enlarged vessels lined with sprouting endothelial cells (EC) and disorganized mural cells. In Sturge Weber Syndrome (SWS), a neurocutaneous disorder, CM occurs in the skin, brain, and eyes. Patients may suffer from seizures, strokes, glaucoma, and only symptomatic treatment is available. CM is caused by a somatic mutation in GNAQ, the gene that encodes the a-subunit of the G-protein – Gaq. The GNAQ mutation – the arginine (R) at the amino acid position of 183 replaced by the glutamine (Q) – is enriched in ECs isolated from CM in the skin, brain, and choroidal vessels of the eye. To date, little is known about how the R183Q point mutation in the Gaq activation domain leads to abnormal capillaries. Moreover, nothing is known about the interactions between the mutant EC and neighboring mural cells surrounding CM vessels. Our preliminary data suggest that lentiviral transduced human EC expressing the R183Q allele (EC-R183Q) have high levels of pro-inflammatory markers, a weaker junctional barrier, and exhibit heightened response to laminar shear stress. Immunostaining of CM tissue sections also reveal disorganization in mural cell environment labeled with Desmin, Calponin, NG2 and alpha-SMA. Moreover, our histological analyses of CM tissue sections revealed MRC1pos, LYVE1pos and CD68pos macrophage-like cells surrounding the CM vessels of the brain and skin suggesting a pro-inflammatory environment. The goal of this fellowship proposal and training plan is to examine how the EC-R183Q interact with both the mural cells and macrophages. I hypothesize that EC- R183Q triggers the disorganized assembly of mural cells and subsequent macrophage attraction to the abnormal vessels. The proposed study will test this hypothesis through the following aims: (1) to identify paracrine interactions between EC-R183Q and mural cells (2) to identify and characterize mural cell and macrophage interactions with EC-R183Q in vivo. Completing these aims will provide new insights into the relationship between EC and the surrounding mural cells and macrophages in the CM. This fellowship training will provide me with technical, communication, and mentoring skills to leverage my next step to independence. Working with Drs. Joyce Bischoff and Arin Greene (co-sponsor) at Boston Children’s Hospital will provide me with an excellent training environment from both the basic science and clinical aspect of the proposed work.


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: 2026 ( Subtotal = -$519 )
2026	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	4/22/2026	NON-COMPETING CONTINUATION	-$519
														Subtotal = -$519

Issue Date FY: 2025 ( Subtotal = $9,072 )
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	2	12/5/2024	NON-COMPETING CONTINUATION	$78,892
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	001	2	7/7/2025	NON-COMPETING CONTINUATION	$1,332
2025	2025	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	002	2	8/22/2025	NON-COMPETING CONTINUATION	-$71,152
														Subtotal = $9,072

Issue Date FY: 2024 ( Subtotal = $76,756 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	002	1	9/13/2024	NEW	$4,964
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	001	1	11/20/2023	NEW	$0
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	11/20/2023	NEW	$71,792
														Subtotal = $76,756

Grand Total All Awards = $85,309

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Endothelial and mural cell interaction in capillary malformation

Award Number: F32HL172637

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/02/2023

PERIOD OF PERFORMANCE END DATE: 01/01/2025

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