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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

Teaching & Training

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

Professional Experience

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

Professional Societies

  • American Society for Biochemistry and Molecular Biology
  • American Heart Association
  • American Physiological Society

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.
  • Mao, G., Dong, Y., Tan, J., Cui, M. Z. and Xu, X.  Both the N-terminal fragment and the protein-protein interaction domain (PDZ domain) are required for the pro-apoptotic activity of presenilin-associated protein PSAP, Biochim Biophys Acta-gen subjects, 2008, 1780(4):696-708. 
  • Tan, J., Mao, G., Cui M.-Z., Kang, S.C., Lamb, B., Wong, B.S., Sy, M.S., Xu, X. Effects of gamma-secretase cleavage-region mutations on APP processing and Abeta formation: interpretation with sequential cleavage and alpha-helical model. J. Neurochem., 2008, 107, 722-733.
  • 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.
  • Mao, G., Tan, J., Cui, M.-Z. Chui, D. and Xu, X. The GxxxG Motif in the Transmembrane Domain of AβPP Plays an Essential Role in the Interaction of CTFbeta with the γ-secretase Complex and the Formation of Ab. Journal of Alzheimer’s Disease, 2009, 18(1):167-76
  • Tan, J., Mao, G., Cui, M.-Z. Lamb, B., Sy, M.-S. and Xu, X. Residues at P2-P1 positions of epsilon- and zeta-cleavage sites are important in formation of beta amyloid peptide. Neurobiology of Disease. 2009, 36(3):453-60
  • 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.