# Mechanoregulation of the Leukocyte Specific Integrin LFA-1 by the Actin Cytoskeleton

> **NIH NIH K01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $169,560

## Abstract

PROJECT SUMMARY
Recruitment of circulating leukocytes to sites of infection plays an important role in the body's defense against
pathogens. Mobilization of leukocytes from the blood to the surrounding tissue occurs in a multistep adhesion
cascade, which is mediated by several adhesion molecule families. The integrin lymphocyte function-
associated 1 (LFA1) mediates firm attachment by binding Intracellular Adhesion Molecules (ICAMs) expressed
by the vascular endothlilium and ultimately leads to transmigration through the vessel wall. The applicant, Dr.
Travis Moore has preformed important studies in this area in the laboratory of Dr. Timothy Springer. The goal
of this application is to deepen Dr. Moore's expertise and findings in this important research area so that it can
be developed into a significant independent research program. Dr. Moore recently lead research to show that
integrin linkage to the actin cytoskeleton and the tensile force generated along the direction of retrograde actin
flow resulted in the orientation of LFA1 on the cell surface. This alignment of LFA1 was substrate dependent
and consistent with integrins being tilted in the same direction as retrograde actin flow. These findings strongly
support a role for the actin cytoskeleton in the regulation of cellular adhesiveness. Dr. Moore will test the
hypothesis that the actin cytoskeleton regulates integrin conformational equilibria and affinity through
mechanical force applied to the integrin cytoplasmic domain and acts as an allosteric effector to stabilize the
high-affinity, extended-open integrin conformation. This work will utilize innovative methodologies to measure
the intrinsic affinities and conformational equilibria of LFA1 and use state-of-the-art super-resolution
microscopy to quantitate the actin cytoskeleton linkage to the integrin cytoplasmic tail and directly measure
integrin conformation on the cell surface of leukocytes. These experiments will advance our understanding of
the regulation of cell adhesiveness and migration, produce novel and innovative methodologies for future
research, and expand Dr. Moore's diverse background with expertise in protein chemistry and purification,
super-resolution microscopy and computational image analysis, genome modification, and quantitating
receptor thermodynamics on the cell surface. Dr. Moore will devote 100 % of his time to this Career
Development Award with Dr. Timothy Springer as his mentor at Boston Children's Hospital.

## Key facts

- **NIH application ID:** 9985152
- **Project number:** 5K01HL143111-04
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Travis I Moore
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,560
- **Award type:** 5
- **Project period:** 2018-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9985152

## Citation

> US National Institutes of Health, RePORTER application 9985152, Mechanoregulation of the Leukocyte Specific Integrin LFA-1 by the Actin Cytoskeleton (5K01HL143111-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9985152. Licensed CC0.

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