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Mei-Zhen Cui
Professor
Biomedical and Diagnostic Sciences

Research Interests

  • Smooth muscle cell gene expression
  • Signal transduction
  • Mechanism of cardiovascular disease

The central objective of the research in our laboratory is to understand the molecular mechanism underlying vascular diseases specifically atherosclerosis and thrombosis. We have found that thrombin activates protein kinase D (PKD) invascular smooth muscle cells. Our results revealed a novel function of PKC d in mediating thrombin-induced PKD activation and identified PKD as a new component in thrombin-induced intracellular signaling pathway in smooth muscle cells. Tissue factor, the initiator of the coagulation cascade, is expressed by cells in atherosclerotic lesions. Our data have shown that lysophosphatidic acid (LPA), a component of oxidized lipoproteins and an agent released by activated platelets, markedly induces tissue factor messenger RNA, tissue factor protein, and tissue factor activity in vascular smooth muscle cells. Activation of MEKs and ERKs mediates LPA-induced TF expression. Our results suggest that elevated LPA could be a thrombogenic risk factor. We are studying the regulation of tissue factor expression by components of oxidized low density lipoproteins and attempting to define the role of oxidized lipids in atherosclerosis and thrombosis.

Education

  • B.S., Jilin University, Changchun, China, 1982, Chemistry
  • M.S., Jilin University, Changchun, China, 1985, Biochemistry
  • Ph.D., Tokyo Institute of Technology, Japan, 1990, Molecular Biology

Professional Experience

  • Postdoctoral Fellow, The Scripps Research Institute, California, 1990-1994, Vascular Biology.
  • Research Associate, Cleveland Clinic Foundation, Ohio, 1995-1999, Vascular Biology.

Teaching & Training

  • Graduate Course CEM 609: Mechanisms of Disease
  • Training graduate students and postdoctoral fellows

Research Interests

  • Phospholipids/growth factors
  • Smooth muscle cell proliferation and migration
  • Endothelial cell dysfunction
  • Foam cell formation
  • Macrophage migration
  • Gene expression
  • Signal transduction
  • Matricellular protein function

The research goal of my laboratory is to understand molecular mechanisms underlying vascular diseases, such as atherosclerosis, restenosis and thrombosis. The focus of our research is to investigate vascular diseases caused by aberrant signaling mechanisms, including extracellular molecule interaction with cell membrane receptors, signal transduction pathways, gene expression and protein modification. We integrate molecular, cellular and genetic approaches to discover the mechanisms that control the progression of atherothrombotic vascular disease.

Selected Awards/Honors and Positions

  • 1998 -Scientist Development Award from the American Heart Association
  • 2002 -Pfizer Basic Research Award
  • 2004 -Philip Morris Research Award
  • 2006 -The University of Tennessee Chancellor’s Award for Research and Creative Achievement
  • 2013 -Editorial Board, Journal of Biological Chemistry

Selected Recent Publications

  • Hao, F., Tan, M., Xu, X., and Cui, M.-Z., Histamine Induces Egr-1 Expression in Human Aortic Endothelial Cells via the H1 Receptor-mediated Protein Kinase Cd-Dependent ERK Activation Pathway, J. Biol. Chem, 2008, 283(40): 26928–26936.
  • Tan, M., Hao, F., Xu, X., Chisolm, G. and Cui, M.-Z., Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocytic THP-1 cell migration, Arterioscler Thromb Vasc Biol., 2009, 29:1376-1382.
  • Hao, F. Tan, M. Wu, D. Xu, X. and Cui, M.-Z., Lysophosphatidic acid induction of interleukin 6 secretion from aortic smooth muscle cells via LPA1 regulated, PKC dependent and p38alpha mediated pathway, American Journal of Physiology-Heart and Circulatory Physiology, 2010, 298(3):H974-83.
  • Wang, Kan; Cai, Lei; Hao, Feng; Xu, Xuemin; Cui, M.-Z.; Wang, Shanfeng, Distinct Cell Responses to Substrates Consisting of Poly(ε-caprolactone) and Poly(propylene fumarate) in the Presence or Absence of Crosslinks. Biomacromolecules, 2010,11(10):2748-59.
  • Cui, M.-Z., (review) Lysophosphatidic acid effects on atherosclerosis and thrombosis. Clinical Lipidology, 2011, 6(4), 413-426.
  • Takuya, I., Zhang, F., Sun, L., Hao, F., Schmitz, C., Xu, X. and Cui, M.-Z., Lysophosphatidic Acid Induces Early Growth Response-1 (Egr-1) Protein Expression via Protein Kinase Cδ-regulated Extracellular Signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) Activation in Vascular Smooth Muscle Cells. J. Biol. Chem. 2012, 287: 22635-22642.
  • Zeng L, Li T, Xu DC, Liu J, Cui M.-Z, Fu X, Xu X. Death Receptor 6 Induces Apoptosis Not through Thype I or Type II Pathways, but via a Unique Mitochondria-dependent Pathway by Interacting with Bax Protein. J. Biol. Chem. 2012, 287(34):29125-33.
  • Mao, G, Cui M.-Z, Li, T, Jin, Y, Xu, X. Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment. J. Neurochem. 2012,123(5):837-44.
  • Hao, F., Wu, D. Xu, X. and Cui, M.-Z.,Histamine induces activation of protein kinase D that mediates tissue factor expression and activity in human aortic smooth muscle cells. American Journal of Physiology-Heart and Circulatory Physiology, 2012, 303(11):H1344-52.
  • Shi, J., Dong, Y., Cui, M.-Z. and Xu, X., Lysophosphatidic acid induces increased BACE1 expression and Abeta formation, Accepted for publication on Biochim Biophys Acta- Molecular Basis of Disease, 2013, 1832(1):29-38.
  • Li, Ting, Zeng, L., Gao, W., Cui, M.-Z., Fu, X. and Xu, X. PSAP induces a unique Apaf-1 and Smac-dependent mitochondrial apoptotic pathway independent of Bcl-2 family proteins. Biochim Biophys Acta- Molecular Basis of Disease. 2013, 1832(3):453-74.
  • Wu, DD, Zhang, F, Hao, F, Chun, J, Xu, X and Cui, M.-Z., Matricellular Protein Cyr61 Bridges Lysophosphatidic Acid and Integrin Pathways Leading to Cell Migration, J. Biol. Chem. 2014, 289(9): 5774-5783.
  • Kimura, TE, Hindmarch, CC, Hewer, RC, Cui, M.-Z., Newby, AC and Bond, M., Inhibition of Egr1 expression underlies the anti-mitogenic effects of cAMP in vascular smooth muscle cells, J Mol Cell Cardiol. 2014, Jul;72:9-19.
  • Zhang, F., Hao, F., An, D., Zeng, L., Wang, Y., Xu, X., and Cui, M.-Z., Matricellular Protein Cyr61 Is a Key Mediator of Platelet-derived Growth Factor-induced Cell Migration, J. Biol. Chem. 2015, 290(13): 8232–8242.
  • Zeng, L., Hu, C., Zhang, F., Xu, DC., Cui, M. Z., and Xu, X., FLIP and PSAP Mediate Presenilin 1-induced γ-secretase dependent and independent apoptosis respectively. J Biol Chem. 2015, 24;290(30):18269-80.
  • Cui, M. Z., (Editorial Focus) Potential therapeutics for myocardial ischemia-reperfusion injury. Focus on "Induction of cardioprotection by small netrin-1 derived peptides". American Journal of Physiology - Cell Physiology. 2015 Jul 15;309(2):C97-9.