Leslie Parise

Research: Cancer, CIB1, Triple Negative, Platelets, Aggregation

Leslie Parise

Professor and Chair of Biochemistry and Biophysics
Joint appointment in Pharmacology
(PhD - University of Illinois, Chicago)

ACCEPTING STUDENTS

120 Mason Farm Road, CB# 7260
3016 Genetic Medicine
Chapel Hill, NC 27599-7260
919-966-2238

Parise Lab Website

HONORS & AWARDS

  • President elect, Assoc of Medical & Graduate Depts of Biochemistry: 2017-2019
  • Candidate, Chair of the Faculty, UNC-CH: 2017
  • Associate Editor, Blood: 2010
  • American Assoc for Biochemistry & Molecular Biology Elected Member, Public Advisory Committee
  • Fellow, American Association for the Advancement of Science
  • Stewart-Niewiarowski Award for Women in Vascular Biology

RESEARCH SUMMARY

Cancer and CIB1: Cancerous cells often proliferate rapidly. Some cancer cell types appear to be addicted to a small intracellular protein, CIB1, for survival. When we deplete CIB1 from several types of cancer cells, including aggressive triple negative breast cancer, the cancer cells die, whereas normal cells remain viable. This depletion disrupts two major cancer-causing pathways. It therefore appears that CIB1 is a promising anti-cancer target. We are pursuing studies to better understand its molecular mechanisms and to develop therapeutic approaches that target CIB1.

Platelets and AADACL1: Platelets are tiny cells that circulate in the blood and aggregate at sites of vessel injury to prevent blood loss. However, if 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. Blocked blood flow causes heart attacks, strokes and related thrombotic disorders, which kill more people each year in the US than any other disease. While there are a number of platelet-inhibiting drugs on the market, all have bleeding as a major side effect. To identify improved anti-platelet targets for drug development, we used a novel screening approach to identify a new enzyme in platelets called AADACL1. AADACL1 inhibition dampens platelet aggregation potentially with an improved profile. We are therefore investigating the molecular mechanism of this enzyme in platelets and in models of thrombosis.

SELECTED PUBLICATIONS

  • Black JL, Harrell JC, Leisner TM, Fellmeth MJ, George SD, Reinhold D, Baker NM, Jones CD, Der CJ, Perou CM, Parise LV. (2015) CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer.  Breast Cancer Res Treat. 152(2):337-46
  • 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 (2013)  Chemoproteomic Discovery of AADACL1 as a Novel Regulator of Human Platelet Activation, Chemistry and Biology, 20(9):1125-34
  • Leisner TM, Moran, C., Holly SP, Parise LV (2013) CIB1 prevents nuclear GAPDH accumulation and non-apoptotic tumor cell death via AKT and ERK signaling. Oncogene, 32:4017-27
  • Leisner T.M., Liu, M., Jaffer, Z.M., Chernoff J., Parise L.V. (2005) Essential role of CIB1 in regulating PAK1 activation and cell migration. J Cell Biol, 170:465-76.
  • Gentry H.R., Singer A.U., Betts L., Ferrara J.D., Yang C., Sondek J. and Parise L.V. (2005) Structure and biochemical characterization of CIB1 delineates a new family of EF-hand containing proteins. J Biol Chem, 280: 8407-8415.

Link to all pubs

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