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Elucidating the role of the tunica adventitia resident progenitor cells in vascular calcification

Award Number: K99HL179387
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Elucidating the role of the tunica adventitia resident progenitor cells in vascular calcification - PROJECT SUMMARY Vascular calcification serves as the primary risk factor for predicting cardiovascular events. It involves arterial calcification, an actively regulated process mediated by cells, resembling physiological biomineralization but with impaired resorption. The vessel wall contains “calcifying vascular progenitor cells” that react to pro- calcific signals such as inflammation or infection. They then differentiate into osteoblast-like cells, which produce minerals and matrix in the vessel wall. The bulk of progenitor cells within the vasculature reside in the microanatomic progenitor niche, the tunica adventitia. Under normal conditions, these progenitors regulate vascular homeostasis and remodeling. The identity, location, function, and regulatory mechanism of adventitial progenitor cells in vascular calcification remain poorly studied. Further, uncovering the niche- specific role of adventitial progenitors in vessel calcification will guide the development of targeted therapeutic strategies. Recently, our integrated transcriptomic study on normal human blood vessel adventitia discovered a cell surface marker to typify adventitial progenitor cells. This previously undescribed marker in adventitial cell biology is Endothelial Protein C Receptor (CD201). CD201-expressing progenitor cells are spatially localized in the outer layer of the adventitia, and their expression level dictates the osteogenic potential of these cells. These recent observations raised questions regarding their role in the progression of vascular calcification and are comprehensively investigated in the present K99/R00 proposal. To achieve this, integrated spatial transcriptomics and single-cell RNA sequencing-based transcriptomic mapping of the human calcified vessel with implications of CD201+CD34+ adventitial cells in calcification will be initially performed. Additionally, reporter mice with nephrectomy-induced calcification will be also examined (Aim 1, K99 Phase). Secondly, a detailed in vitro functional characterization of FACS purified CD201High/Low cells from human calcified and healthy vessels will be performed, along with CD201 cell ablation in mouse calcification model to determine the functional role of the cell in calcification (Aim 2, K99 Phase). Lastly, the underlying signaling mechanism regulating CD201-expressing cells to be pro-calcific is investigated by CRISPR/Cas9 gene knockdowns, genetic mice calcification models, and integrated transcriptomics (Aim 3, R00 phase). Completing the proposal will greatly improve the knowledge of adventitial progenitor cell-mediated vessel calcification. The proposed research and training plan aligns with my long-term research objective. It will also significantly contribute to my scientific and career goals of establishing an independent research career in blood vessel resident stem cells and their role in vascular pathology.


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 = $93,085 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	1	3/30/2026	NEW	$93,085
														Subtotal = $93,085

Grand Total All Awards = $93,085

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Elucidating the role of the tunica adventitia resident progenitor cells in vascular calcification

Award Number: K99HL179387

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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