Leslie V. Parise

Leslie V. Parise

Professor and Chair

Department of Biochemistry & Biophysics

Ph.D., Pharmacology
University of Illinois Medical Center, Chicago, IL

Biosketch [.pdf]

Parise Lab Website
Biochemistry & Biophysics Department

Contact Information  ->>

Research Interests

  • Cell-surface adhesion proteins.
  • Role of integrins and cell signaling in cardiovascular disease and cancer.

Research Synopsis

The Parise lab studies the roles of adhesion receptors and signaling in several aspects of cardiovascular disease and cancer

Platelets

Heart attacks, strokes and related thrombotic disorders kill more people each year in the US than any other disease. Circulating platelets, which normally aggregate at sites of vascular injury to prevent blood loss, causes these thrombotic events. Under pathologic conditions, when the blood vessel has formed cholesterol-containing atherosclerotic plaques, these plaques can rupture, causing platelets to aggregate at these sites, potentially completely blocking blood flow. The lab is currently mapping signal transduction pathways that lead to the activation of 2 different integrins, αIIbβ3 and α2β1. The lab is studying both integrin cytoplasmic domain binding proteins (e.g. CIB) as well as small G-proteins (R-Ras and Rap1) to understand how these proteins relay information to these integrins to regulate their activation state.

Sickle Cell Disease

Sickle cell patients suffer from painful vaso-occlusive crises, which are believed to be due to sickle red cell adhesion to the blood vessel wall. This adhesion blocks blood flow in capillaries and causes severe pain and organ damage. Our lab is interested in understanding the mechanisms of the vaso-occlusive crisis. We previously demonstrated that sickle cells adhere to the large adhesive proteins thrombospondin (TSP) and laminin, which are found in the blood and blood vessel wall. More recently, we have discovered that the sickle cell has the ability to upregulate its state of adhesion in response to physiologic/pathologic agonists such as TSP and epinephrine. This is an important discovery, since signal transduction pathways in sickle cells are not well characterized, but are likely to provide therapeutic targets to control vaso-occlusive crises. Current broad project areas include:

Cancer

If breast epithelial cells become cancerous or transformed, they become more migratory and invasive and lose their ability to form differentiated, polarized breast ducts. Molecular mechanisms by which breast epithelial cells acquire a transformed phenotype are not well understood. However, integrin adhesion receptors on breast epithelial cells, especially the α2β1 integrin, mediate the increased migration and invasion of these cells through extracellular matrix proteins such as collagen. Our lab is interested in mapping signal transduction pathways in transformed cells that cause integrins to mediate increased cellular migration and invasion. Intracellular signaling molecules of interest include members of the Ras superfamily of small G-proteins. These small G-proteins or GTPases act as molecular switches in cells and are crucial for transmitting fundamental biologic information in cells, regulating everything from rates of cell proliferation, to cytoskeletal structure and states of integrin activation. We have found that some of these small G-proteins (R-Ras, TC21, Cdc42 and Rac) cause breast epithelial cells to acquire a transformed phenotype, but by very different mechanisms. In ongoing studies we are trying to understand the different mechanisms of transformation by mapping the signaling pathways involved.

See the Parise Lab Website for more information.
See Journal of Cell Biology Cover

Publications

pubmed

Click above for PubMed publications.

Contact Information


Office Location:
3016 Genetic Medicine

Mailing Address:
CB # 7260
UNC-CH School of Medicine
Chapel Hill, NC 27599-7260

Office Phone: 919-966-2238
Lab Phone: 919-962-1058
Fax: 919-966-2852
parise[at]med.unc.edu

 

 

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