Professor & Chair of Biochemistry and Biophysics
PhD - University of Illinois, Chicago
HONORS AND AWARDS
- American Assoc. for Biochemistry & Molecular Biology Elected Member, Public Advisory Committee
- Association of Medical & Graduate Departments of Biochemistry, Board of Directors
- Member, AHA MidAtlantic Research Council
- Permanent Member, NIH HT Study Section
- Associate Editor, Blood
- Fellow, American Association for the Advancement of Science
- Stewart-Niewiarowski Award for Women in Vascular Biology
- Fellow, Executive Leadership in Academic Medicine
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.
CIB1 and Cancer
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 or angiogenesis. An ideal anti-cancer target would prevent both angiogenesis and tumor cell proliferation. CIB1 is a small calcium binding protein that is expressed in multiple cell types, including endothelial cells and cancer 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 and tumor growth is impaired. In addition, if CIB1 levels are decreased in breast cancer cells and neuroblastoma, these cells die by an unusual mechanism. These properties therefore make CIB1 a promising anti-cancer target.
- Freeman, TC, Black, JL, Bray, HG, Dagliyan, O, Wu, YL, Tripathy, A, Dokholyan, NV, Leisner, TM, Parise, LV: Identification of novel integrin binding partners for CIB1: structural and thermodynamic basis of CIB1 promiscuity. Biochemistry. 2013, In press
- Holly SP, Chang JW, Li W, Niessen S, Phillips R,Piatt R, Black JL, Smith M, Boulaftali Y, Weyrich A, Bergmeier W, Cravatt BF and Parise LV: Chemoproteomic Discovery of AADACL1 as a Novel Regulator of Human Platelet Activation, Chemistry and Biology, 2013, In press
- Desai PC, Brittain JE, Jones SK, McDonald A, Wilson DR, Dominik R, Key NS, Parise LV, Ataga KI: A Pilot Study of Eptifibatide for Treatment of Acute Pain Episodes in Sickle Cell Disease, Thromb Hemost 2013, In press
- Xie L., Liu, C., Wang, L., Gunawardena, H.P., Yu, Y., Du, R., Taxman, D.J., Dai, P.,Yan, Z., Yu, J., Holly, S.P., Parise, L.V., Wan, Y., Ting, J.P. and X. Chen. (2013). ProteinPhosphatase 2A Catalytic Subunit α Plays a MyD88-Dependent, Central Role in theGene-Specific Regulation of Endotoxin Tolerance. Cell Reports 2013 Feb 19, e-pub ahead of print
- Leisner TM, Moran, C., Holly SP Parise LV: CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling. Oncogene, 2013 32:4017-27 [Epub ahead of print, 2012 Sep 10.] PMCID:PMC3530648
- Xie L, Liu C, Wang L, Gunawardena HP, Yu Y, Du R, Taxman DJ, Dai P, Yan Z, Yu J, Holly SP, Parise LV, Wan YY, Ting JP, Chen X. Protein phosphatase 2A catalytic subunit α plays a MyD88-dependent, central role in the gene-specific regulation of endotoxin tolerance. Cell Rep. 2013 Mar 28;3(3):678-88.
- Riazuddin, S, Belyantseva, IA, Giese A, Lee K, Indzhykulian AA, Nandamuri SP. Yousaf , R, Lee S, Terrell, D, Hegde RS, Husnain RA, Khan SN, Parise LV, Basit S, Wali A, Ayub M, Ansar M, Swaroop A, Ahmad W, Tekin M, Riazuddin , Cook T, Buschbeck EK, Frolenkov GI, Leal SM, Friedman TB, Ahmed ZM: Mutations of CIB2, a calcium and integrin binding protein, cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. Nature Genetics, 2012 Nov;44(11):1265-71.
- Leisner TM, Moran, C., Holly SP Parise LV (2012) CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling. Oncogene, 2012 Sep 10.
- Willis MS, Homeister JW, Rosson GB, Annayev Y, Holley D, Holly SP, Madden VJ, Godfrey V, Parise LV, Bultman SJ. Functional Redundancy of SWI/SNF Catalytic Subunits in Maintaining Vascular Endothelial Cells in the Adult Heart. (2012) Circ Res 111: e111-22.
- Chantrathammachart P, Mackman N, Sparkenbaugh E, Wang J-G, Parise LV, Kirchhofer D, Key NS, and Pawlinski R. (2012) Tissue Factor Promotes Activation of Coagulation and Inflammation in a Mouse Model of Sickle Cell Disease. Blood 120:636-46
120 Mason Farm Rd,
Campus Box # 7260
3016 Genetic Medicine
Chapel Hill, NC 27599
Lab Location: 2070F Genetic Med