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Defining how cell adhesion supports blood cell development

Award Number: F31HL186637
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/06/2027
PERIOD OF PERFORMANCE END DATE: 02/05/2028

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Defining how cell adhesion supports blood cell development - PROJECT SUMMARY Endothelial-to-hematopoietic transition (EHT) is a key cell differentiation process in developmental hematopoiesis because it gives rise to the source of hematopoietic stem and progenitor cells (HSPCs) that allows for blood cell production throughout embryonic and adult life. Much of the transcriptional programming affecting the differentiation of blood cells during development has been established. However, the structural biology and adhesion-dependent mechanisms that govern hemogenic endothelial cell (HEC) morphogenesis during EHT remain poorly understood. During this process, a small population of vascular endothelial cells within the arterial vascular niche will gain blood-forming potential and will undergo drastic transcriptional and morphological changes to become HSPCs. The arterial vascular niche provides essential extrinsic cues for HECs to support HSPC formation and engraftment. EHT shares several characteristics with other cell transition processes, suggesting that conserved biomechanical and cytostructural transformations may be regulated. Cell adhesion complexes, particularly tight junctions, are essential for maintaining arterial vascular barrier integrity and polarity yet must be dynamically remodeled to accommodate hematopoietic emergence. Preliminary transcriptomic profiling of cells undergoing EHT revealed dynamic changes in adhesion complex gene expression, including a striking enrichment of claudin-5 (CLDN5), a tight junction protein, in HECs that is rapidly lost following hematopoietic emergence. Immunofluorescence studies of iPSC-derived cultures confirm CLDN5 localization in vascular structures containing RUNX1+ HECs. I hypothesize that structural changes in tight junction complexes and actin cytoskeletal remodeling enable HEC emergence and hematopoietic specification. In Aim 1, I will determine how tight junction complexes regulate HSPC formation and EHT by characterizing junction dynamics in iPSC-derived HECs via high-resolution microscopy, generating computational models to simulate EHT-like scenarios, and identifying transcriptional regulators of tight junction genes using ATAC-seq. In Aim 2, I will define how CLDN5 modulates EHT using endothelial-specific knockout mouse models and small-molecule inhibitors in vitro to assess effects on HEC formation, HSPC output, and functional potential. Together, these studies will uncover how adhesion-mediated structural remodeling regulates hematopoietic emergence and inform new strategies to optimize HSPC generation in vitro for therapeutic uses. This fellowship will provide essential support to strengthen my interdisciplinary research skills and advance my development into an independent investigator in stem cell biology and regenerative medicine.


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 = $50,114 )
2026	2026	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	1	8/11/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Defining how cell adhesion supports blood cell development

Award Number: F31HL186637

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/06/2027

PERIOD OF PERFORMANCE END DATE: 02/05/2028

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