Wednesday, July 30, 2025 7/30/2025

Regulation of endothelial cell invasion, migration and cell junction plasticity

Award Number: R35GM145318
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

Group Awards By:

View Award Description

Regulation of endothelial cell invasion, migration and cell junction plasticity - Project Summary One of the main research directions of my laboratory focuses on regulation of the endothelial barrier and endothelial cell migration. These processes are critical for physiological function of vascular system and they are often dysregulated in human diseases. A lot of progress has been made in understanding signaling that regulates endothelial barrier and cell migration. However, stimulation of endothelial cell migration during angiogenesis is a highly localized and transient event. Defining the role of the local and temporal components of angiogenic signaling has been challenging due to limitations of current tools. Furthermore, spatiotemporal regulation of the endothelial barrier by these stimuli has been poorly understood. Our proposed work will focus on determining how the location and duration of migratory signals direct endothelial cell invasion and migration through extracellular matrix, and how they affect the organization and permeability of the endothelial barrier. The endothelial barrier is controlled at the level of adherens junctions (AJs), cell-cell adhesion structures mediated by the transmembrane protein VE-cadherin. Phosphorylation-mediated signaling regulates the structure and permeability of AJs. In our recent studies, we described a dual role of tyrosine kinase Src and its phosphorylation of VE-cadherin in regulation of endothelial permeability. Our results demonstrated that Src- mediated phosphorylation induces formation of dynamic AJs that still retain their barrier function. This suggests a mechanism for the regulation of AJ plasticity that does not compromise barrier permeability during endothelial cell migration. In parallel studies, we dissected a mechanism of Src-regulated degradation of the extracellular matrix by the endothelial cell and discovered a novel cytoskeletal component that mediates formation of matrix-degrading podosomes. The studies proposed here will continue to build on our previous findings and focus on dissecting how phosphorylation of VE-cadherin and angiogenic signaling by Vascular Growth Factor Receptor 2 (VEGFR2), Sphingosine-1-phosphate Receptor 1 (S1PR1), and Src regulate plasticity of AJs as well as invasion and migration of endothelial cells. We will employ novel optogenetic tools that will allow us to interrogate these processes with precise spatial and temporal control. We will use engineered light-regulated VEGFR2, S1PR1, and Src to determine the effects of locally and temporally controlled angiogenic signals and dissect mechanisms that mediate regulation of AJs and migration of endothelial cells in three dimensional environment. Our long-term goal is to define the processes that control migration of endothelial cells and endothelial barrier function during angiogenesis.


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 = $399,750 )
2025	2025	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	001	4	7/8/2025	NON-COMPETING CONTINUATION	$399,750
2025	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	3	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $399,750

Issue Date FY: 2024 ( Subtotal = $649,750 )
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	001	3	7/17/2024	SUPPLEMENT FOR EXPANSION	$250,000
2024	2024	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	3	7/16/2024	NON-COMPETING CONTINUATION	$399,750
														Subtotal = $649,750

Issue Date FY: 2023 ( Subtotal = $399,750 )
2023	2023	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD AVE M/C 551	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	2	7/18/2023	NON-COMPETING CONTINUATION	$399,750
														Subtotal = $399,750

Issue Date FY: 2022 ( Subtotal = $399,750 )
2022	2022	UNIVERSITY OF ILLINOIS	809 S MARSHFIELD RM 520	CHICAGO	IL	60612	COOK	USA	Biomedical Research and Research Training	000	1	8/18/2022	NEW	$399,750
														Subtotal = $399,750

Grand Total All Awards = $1,849,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Regulation of endothelial cell invasion, migration and cell junction plasticity

Award Number: R35GM145318

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer