# Cellular Mechanisms of Inflammation, Hemostasis, and Thrombosis

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $2,340,324

## Abstract

ABSTRACT
Support is requested for an interdisciplinary effort to understand the key molecular and
developmental events that regulate blood and vascular cells in inflammation, hemostasis
and thrombosis with a focus on adhesive signaling. The four Projects will: 1) Test the
hypothesis that direct interactions between Rap1 and talin1 plays an important role in
platelet, leukocyte, and endothelial cell functions in inflammation, hemostasis and
thrombosis. 2) Use newly developed imaging modalities to enable quantitative dynamic
footprinting of the surface of neutrophils in contact with substrate to assess adhesion
receptor clustering and conformation in response to specific molecular adaptor-adhesion
receptor interactions. A particular focus is the structure-function of kindlin-3, the gene
mutated in human leukocyte adhesion deficiency Type 3, and its relationship to talin. 3)
An Early Stage Investigator will test the hypothesis that genetic inactivation of Krit1 or
Heg1 in adult mice will protect against experimental inflammation or thrombosis. In
collaboration with a structural biologist, he will extend studies to test the feasibility of
pharmacologically disrupting the HEG1-KRIT1 complex to mimic the effects of genetic
inactivation of these genes. 4) To assess the role of SHARPIN and associated
components of the LUBAC linear ubiquitination complex in the functions of platelets and
endothelial cells in inflammation, hemostasis, and thrombosis. This project will test the
hypothesis that this newly-identified regulator of platelet and endothelial cell functions
contributes to inflammation, hemostasis, and thrombosis. A scientific core unit, led by a
world leader in murine models of inflammation, hemostasis, and thrombosis, will provide
the individual projects with in vivo models and expertise required to establish the patho-
physiological relevance of these novel molecular mechanisms.

## Key facts

- **NIH application ID:** 10229365
- **Project number:** 5P01HL151433-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Mark HOWARD Ginsberg
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,340,324
- **Award type:** 5
- **Project period:** 2020-08-05 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229365

## Citation

> US National Institutes of Health, RePORTER application 10229365, Cellular Mechanisms of Inflammation, Hemostasis, and Thrombosis (5P01HL151433-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229365. Licensed CC0.

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