# Cell Adhesion and Signaling in Blood and Vascular Cells

> **NIH NIH P01** · CLEVELAND CLINIC LERNER COM-CWRU · 2022 · $2,430,557

## Abstract

Project Summary
This application has as its theme the integrins, their regulation and their contribution to the functional
responses of blood and vascular cells. The integrins of focus are αMβ2 (Mac-1), αIIbβ3, αVβ3, and α5β1
but findings should apply to broadly integrins. The cells of emphasis are vascular cells- endothelial cells,
smooth muscle cells and pericytes- and blood cells- leukocytes and platelets. On the blood cells, the
conjugation of Mac-1 on leukocytes and GPIb on platelets will be considered. Major emphasis will be
placed on the molecules that regulate integrin function- kindlins, talin and paxillin- to determine how they
collaborate to regulate integrin activation. The function of these cytoskeletal proteins independent of
integrin activating activity will also be dissected. The Program consists of three projects, each directed by
an accomplished faculty member at their home institutions, Cleveland Clinic, University Hospitals of
Cleveland and Case Western Reserve University which are all closely located and governed by
interinstitutional agreements. Dr. Edward F. Plow, Ph.D. will serve as Program Director and lead Project
1. This project deals with the mechanisms by which kindlin-2 regulates both integrin-dependent and
independent responses of blood vessel cells. Molecular, cellular and unique mouse models are all brought
to bear to determine how kindlin-2 serves as a master regulator of vascular cell responses. In Project 2,
Dr. Jun Qin will use high resolution structural approaches in combination with mutagenesis and cellular
studies to determine how talin regulate integrin activation and cooperates with kindlins and paxillin to gain
such novel insights. He will determine how talin interacts with actin to control organization of the
cytoskeleton. Dr. Daniel Simon, M.D. will lead Project 3 and will consider how engagement of integrin
Mac-1 on leukocytes and GPIb on platelets regulates the participation of these cells in inflammation and
thrombosis. His studies range from basic structural approaches to translational studies in mice and to
humans to provide insights into their thrombotic and inflammatory contributions to systemic lupus
erythematosus. The Program is supported by two Scientific Cores, Protein Expression and Purification
(Core B), and Animal Models and Tissue Analysis (Core C) as well as by an Administrative Core (AC1). A
common objective of the Program is to continue and create new collaborations among the Projects and
their Leaders to resolve the structural and biological mechanisms that regulate the functions of integrins in
blood and vascular cells. The information derived from these studies will provide insights into biologically
important responses regulated by integrins and their activation that are relevant to thrombosis and
cardiovascular diseases.

## Key facts

- **NIH application ID:** 10471908
- **Project number:** 5P01HL154811-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** JUN QIN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,430,557
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471908

## Citation

> US National Institutes of Health, RePORTER application 10471908, Cell Adhesion and Signaling in Blood and Vascular Cells (5P01HL154811-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10471908. Licensed CC0.

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