Abstract

Support is requested to continue a program designed to advance understanding of molecular mechanisms of vascular disease and to promote development of new diagnostic, therapeutic, and preventive strategies through the collaborative efforts of a group of experienced scientists focused on the unifying theme of cell adhesion. This group of scientists, with a history of productive collaborative interactions, will cooperate in studies directed at the unifying theme. To understand the regulation of platelet, endothelial cell, and leukocyte adhesion, we propose studies ranging from analysis of protein structure at atomic level of detail through biochemistry, cell biology, ex-vivo studies to analyze the effects of blood flow on adhesion and signaling, nanoscale resolution of integrin conformational changes and adaptor recruitment in live rolling neutrophls, and analysis of genetically-modified mice and zebrafish.

Public Health Relevance

This program will advance understanding of molecular mechanisms of vascular disease and promote development of new diagnostic, therapeutic, and preventive strategies by studying the regulation of cell adhesion by cells of the blood and vessel wall.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL078784-12
Application #
9044809
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Kindzelski, Andrei L
Project Start
2004-12-01
Project End
2020-04-30
Budget Start
2016-05-06
Budget End
2017-04-30
Support Year
12
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Klann, Jane E; Kim, Stephanie H; Remedios, Kelly A et al. (2018) Integrin Activation Controls Regulatory T Cell-Mediated Peripheral Tolerance. J Immunol 200:4012-4023
Weijts, Bart; Gutierrez, Edgar; Saikin, Semion K et al. (2018) Blood flow-induced Notch activation and endothelial migration enable vascular remodeling in zebrafish embryos. Nat Commun 9:5314
Sun, Hao; Lagarrigue, Frederic; Gingras, Alexandre R et al. (2018) Transmission of integrin ?7 transmembrane domain topology enables gut lymphoid tissue development. J Cell Biol 217:1453-1465
Marki, Alex; Buscher, Konrad; Mikulski, Zbigniew et al. (2018) Rolling neutrophils form tethers and slings under physiologic conditions in vivo. J Leukoc Biol 103:67-70
Moccetti, Federico; Brown, Eran; Xie, Aris et al. (2018) Myocardial Infarction Produces Sustained Proinflammatory Endothelial Activation in Remote Arteries. J Am Coll Cardiol 72:1015-1026
Lagarrigue, Frederic; Gingras, Alexandre R; Paul, David S et al. (2018) Rap1 binding to the talin 1 F0 domain makes a minimal contribution to murine platelet GPIIb-IIIa activation. Blood Adv 2:2358-2368
Wolf, Dennis; Anto-Michel, Nathaly; Blankenbach, Hermann et al. (2018) A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense. Nat Commun 9:525
Lopez-Ramirez, Miguel Alejandro; Fonseca, Gregory; Zeineddine, Hussein A et al. (2017) Thrombospondin1 (TSP1) replacement prevents cerebral cavernous malformations. J Exp Med 214:3331-3346
Ye, Feng; Yang, Chansik; Kim, Jiyoon et al. (2017) Epigallocatechin gallate has pleiotropic effects on transmembrane signaling by altering the embedding of transmembrane domains. J Biol Chem 292:9858-9864
Rothmeier, Andrea S; Marchese, Patrizia; Langer, Florian et al. (2017) Tissue Factor Prothrombotic Activity Is Regulated by Integrin-arf6 Trafficking. Arterioscler Thromb Vasc Biol 37:1323-1331

Showing the most recent 10 out of 125 publications