Home / Research / Center for Metabolic and Vascular Biology / Center Metabolic and Vascular Biology / Ugarova Lab

Ugarova Lab

 
 
 
Personnel: 
Tatiana Ugarova, Ph.D.
Associate Professor, School of Life Sciences, Arizona State University, Center for Metabolic and Vascular Biology
 
Description: 

Research in the Ugarova laboratory focuses on the elucidation of cellular and molecular mechanisms of cell adhesion with a particular focus on the role of integrin receptors in adhesive interactions of leukocytes and platelets in thrombosis and inflammation. Inflammation is now recognized as being central not only in normal protective host response during infection but also critical in the regulation of homeostatic functions in many tissues. Nevertheless, chronic inflammation is associated with the development of many diseased conditions such as obesity, insulin resistance, hypertension, and atherosclerosis. A hallmark of inflammation is the migration of leukocytes from the peripheral blood and their accumulation and activation within tissues.

Research in the laboratory focuses on the member of the b2 sub-family of integrin adhesion receptors aMb2 (Mac-1, CD11b/CD18) which mediates leukocyte adhesion, migration, and also regulates numerous leukocyte effector functions. Of intense interest are the mechanisms by which Mac-1 on macrophages controls adiposity. Macrophages are present in higher numbers in adipose tissue of obese than lean subjects and thought to be the main culprit responsible for obesity-induced insulin resistance. Our recent findings challenge the generality of this idea by providing evidence that macrophages in fat regulate and maintain adiposity in normal non-inflamed fat. In particular, we have been intrigued by our recent discovery that while adipose tissue in integrin Mac-1-deficient mice contains significantly less macrophages, these animals are spontaneously obese. We are exploring the hypothesis that deficiency of Mac-1 impacts migration and/or retention of resident macrophages within adipose tissues where they exert their effect on proliferation of adipocyte precursors. For example, we found that macrophages isolated from fat of Mac-1-deficient mice exhibit decreased expression of genes characteristic of M2-phenotype (alternatively activated) and increased expression of TNFa, a marker of M1-like proinflammatory macrophages. A recently initiated project investigates the role of integrins in macrophage fusion, a salient event in obesity-induced inflammation which was proposed to limit the expansion of adipocytes. Our data show that fusion of macrophages isolated from Mac-1-deficient mice is severely impaired, implicating Mac-1 as a critical component of the fusion reaction. The figure shows fusion of wild-type and Mac-1-deficient macrophages (labeled with red and green PKH dyes) induced by IL-4.

Our efforts are also directed toward analyzing integrin-mediated platelet adhesion in thrombus formation and the role of platelet-fibrinogen interactions in blood compatibility of vascular grafts.

The types of analyses employed in the laboratory range from basic studies of integrin structure using molecular biology and biochemistry techniques, to investigation of molecular and cellular mechanisms of their function in cell culture, to studies conducted in animal models of inflammation, obesity, and thrombosis. A recent addition to the arsenal of techniques is nanotechnology, including AFM-based imaging, nanolotigraphy, molecular and single-cell force spectroscopy, which allows for accurate quantification of forces developed between cellular integrins and their extracellular matrix ligands. The research in the Dr. Ugarova laboratory has been supported by the National Institutes of Health.

Laboratory Members

Research Faculty
Valeryi Lishko, Ph.D.
Nataly Podolnikova, Ph.D.

Postdoctoral Fellows
Ivan Yermolenko, Ph.D.
YiFei Wu, Ph.D.
Ramya Turaga, Ph.D.
James Faust, Ph.D.

Technical Staff
George Vo, B.S.

Ph.D. Students
Hadil Owaynat
Kyu Beom Oh
Roman Safiullin