Professor of Biochemistry and Biophysics, UNC-CH Chair of Biochemistry and Biophysics, UNC-CH Professor of Pharmacology, UNC-CH (joint appointment) PhD - University of Illinois, Chicago (click for full publication list)

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HONORS AND AWARDS

• Fellow, American Association for the Advancement of Science
• Stewart-Niewiarowski Award for Women in Vascular Biology
• Fellow, Executive Leadership in Academic Medicine

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RESEARCH

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, also induce these thrombotic events. Under pathologic conditions, when the blood vessel has formed cholesterol-containing atherosclerotic plaques, these plaques can rupture, causing platelets become activated and aggregate at these sites, potentially completely blocking blood flow. We wish to better understand the biochemical pathways and mechanisms involved in platelet aggregation in order to identify new targets for drug development.

Sickle Cell Disease

Sickle cell patients suffer from painful vaso-occlusive crises, which are believed to be due to the abnormal adhesion of multiple blood cell types to the blood vessel wall. These cell types appear to include the red cells themselves, white cells and platelets. 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 discovered that the sickle cell has the ability to upregulate its state of adhesion in response to physiologic/pathologic agonists such as thrombospondin and epinephrine. This is an important discovery, since signal transduction pathways in sickle cells are not well characterized, but are likely to provide drug targets to control vaso-occlusive crises.

Cancer, Endothelial Cells, and CIB1

Cancerous tumor cells often proliferate rapidly. Once tumors grow beyond a few mm in size, they require blood vessels to provide nourishment in order to grow further. Endothelial cells are essential for blood vessel formation. CIB1 is a small calcium binding protein that is expressed in multiple cell types, including endothelial cells, and appears to be a very important regulatory molecule. For example, CIB1 binds to multiple serine/threonine kinases and some other types of proteins to regulate their function. We found that efficient tumor-induced blood vessel growth depends upon CIB1. If endothelial cells do not express CIB1, the cells grow more slowly and tumor-induced blood vessel formation is impaired. We have also generated a CIB1 knockout mouse and studied the consequences of a lack of CIB1 on tumor growth in vivo.

• Holly SP, Chen X, Parise LV: Abundance- and Activity-Based Proteomics in Platelet Biology. Current Proteomics. 2011. 8:216-228.

• Holly SP, Parise LV: Big Science for Small Cells: Systems Approaches for Platelets. Current Drug Targets, 2011 Jun 30.

• Leisner TM, Parise LV: Talin's second act-ivation: retraction, Blood. 2011 Feb 3;117(5):1442-3

• Williams MS, Weiss EJ, Sabatine MS, Bray PF, Simon DI, Bahou WF, Becker LC, Parise LV, Dauerman HL, French PA, Becker RC, Smyth SS. Genetic regulation of platelet expression and function: application in clinical practice and new drug development. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2372-84.

• Zayed MA, Yuan W, Chalothorn D, Faber JE, Parise LV. Tumor growth and angiogenesis is impaired in CIB1 knockout mice. J Angiogenes Res. 2010 Aug 30;2(1):17

• Heineke J, Auger-Messier M, Correll N, Xu J, Benard MJ, Yuan W, Parise LV, Molkentin JD: CIB1 is a Novel Regulator of Pathological Cardiac Hypertrophy. Nat Med, 2010 Aug;16(8):872-9.

• Demorest ZL, MacDuff DA, Brown WL, Morham SG, Parise LV, Harris RS: The Interaction Between AID and CIB1 is Nonessential for Antibody Gene Diversification by Gene Conversion or Class Switch Recombination. PLoS ONE, 2010 Jul 20;5(7):e11660

• Wang Z, Holly SP, Larson MK, Liu J, Yuan W, Chrzanowska-Wodnikcka M, White GC, Parise LV. Rap1b is critical for glycoprotein VI-mediated but not ADP receptor-mediated alpha2beta1 activation. J Throbm Haemost. 7:693-700, 2009