# Deconvoluting the Vascular Adhesome

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $786,958

## Abstract

Summary
Integrin-based adhesions are central to the functions of blood and vascular cells. The
heterogeneity of adhesions and their dynamic evolution has complicated efforts to study their fine
composition, assembly, and disassembly. Our studies have shown that a transition between two
adhesion archetypes is controlled by a simple binary molecular switch of vinculin competition with
and displacement of RIAM or lamellipodin(Lpd), members of the MRL family, from binding sites
on talin's rod domain. Furthermore, we developed methods to image the complex of MRL proteins
with integrins and talin (MIT complex) and showed that it formed the tips of “sticky fingers,” cellular
protrusions that sense the density of matrix proteins and physical state of the substrate during
mesenchymal cell migration. mesenchymal cell migration. We hypothesize that the MIT
complex represents one among many distinct modules that contribute to the overall
structure and function of integrin- based adhesions. This suggests the paradigm that the
integrin adhesome can be analyzed as a dynamic assembly of these modules, which form prior to
entry into the adhesions. This concept has enabled us to propose a new approach to studying
adhesions by developing methods to purify each module formed prior to integrin ligation. To test
this paradigm, we propose to purify 4 such modules and to characterize each for a) the presence
of talin-activated integrins b) characterize its protein composition. c) establish its biochemical
topology and regulation d) visualize it in living cells and e) evaluate its functions The proposed
experiments will generate foundational data for the adhesion field in three ways: a) the integrin
adhesome will be re- interpreted as a compendium of modular components; each with its own
specific composition. b) The functional studies will identify new regulators of blood and vascular
cell adhesion and signaling that may be exploitable as therapeutic targets c) A complete definition
of the protein composition of each module will serve as a public resource for the analysis of
integrin-based adhesions and will be hypothesis-generating for future studies to understand the
regulation of assembly of each module and its functional outputs.

## Key facts

- **NIH application ID:** 10548841
- **Project number:** 5R35HL139947-06
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Mark HOWARD Ginsberg
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $786,958
- **Award type:** 5
- **Project period:** 2018-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10548841

## Citation

> US National Institutes of Health, RePORTER application 10548841, Deconvoluting the Vascular Adhesome (5R35HL139947-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10548841. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*