Kafait U. Malik, D.Sc., Ph.D.
Professor of Pharmacology (Cardidovascular Disease)

Education:

• 1964 D.Sc., Pharmaceutical Technology, University of Zagreb, Zagreb,Yugoslavia (Now Croatia)
• 1966 M.Sc., Ph.D. Pharmacology, University of Sarajevo, Sarajevo,Yugoslavia (Now Bosnia & Hercegovina)
• 1966-1967 Postdoctoral Trainining, Institute of Pharmacology, Faculty of Medicine, Johanes-Gutenberg University of Mainz, West Germany
• 1967-1970 Postdoctoral Training, Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ottawa, Canada

Position:

• Professor of Pharmacology, College of Medicine, University of Tennessee Health Science Center
• Director, NIH Training Grant "Lipid/Lipoprotein Metabolism and Cardiovascular Diseases

Contact Information:

Phone: 901-448-6075
Fax: 901-448-7206
Email: kmalik@utmem.edu

Mailing Address:

Research Keywords:

Pharmacology, Physiology, Molecular Biology, Vascular Biology, Vascular Smooth Muscle, Vascular Smooth Muscle and Endothelial Cells, Vascular Reactivity, Endothelial Dysfunction, Nitric Oxide, Nitric Oxide Synthase, Adrenergic Nervous System, Renin-Angiotensin System, Angiotensin II, Angiotensin Converting Enzyme 2, Growth Factors, Lipids, Phospholipase A2 and D2, Cyclooxygenase, Lipoxygenase, Cytochrome P450 A, B and C, Eicosanoids, Prostanoids, hydroxyeicosatetraenoic acids (HETEs), Epoxyeicosatetraenoic Acids , (EETs), Signal Transduction Mechanisms, Serine-Threonine and Tyrosine Kinases, Vascular Smooth Muscle and Endothelial Cell Proliferation and Hypertrophy, Restenosis, Atherosclerosis, Hypertension and Diabetes

Research Specialty:

Cellular and Molecular Mechanisms Involved in the Action of Norepinephrine, Angiotensin II and Growth Factors on Vascular Reactivity, Vascular and Endothelial Cell Proliferation and Hypertrophy, Restenosis, Atherosclerosis and Hypertension and Diabetes

Research Interests:

The overall objective of our research is to elucidate the cellular and molecular signal transduction mechanisms of growth factors, circulating hormones including angiotensin II (Ang II) and locally generated autacoids (eicosanoids) and adrenergic transmitter norepinephrine (NE) in the regulation of cardiovascular function in health and in the development of hypertension and vasculopathy associated with restenosis, atherosclerosis and diabetes.   Our studies should further our knowledge of the neuro-humoral mechanisms that regulate vascular function and its alteration in vascular diseases.  Moreover, these studies should allow formulating rational approaches for the development of novel therapeutic agents for the treatment of hypertension, arteriosclerosis and restenosis.

We use isolated cultured vascular smooth muscle and endothelial cells, isolated perfused organs (heart, kidney and blood vessels), wire myogrph for measuring vascular reactivity models of hypertension (Ang II- and DOCA-Salt and SHR), balloon injured carotid artery and now we are also transgenic animals for our studies. The laboratory techniques also include the use of HPLC-GC-Mass spectrometric Analysis of Eicosanoids, SDA-PAGE and Western blot analysis, DNA and RNA isolation, purification and quantitation, PCR, RT-PCR, Q-PCR, DNA transfection in cells Plasmid preparation, restriction fragment mapping, Construction of siRNA of various signal molecules, Transfection of reporter vectors as well as over-expression of constitutively active or dominant negative proteins, Co-immunoprecipitation and co-localization techniques, con-focal microscopy, site direct mutagenesis Molecular imaging of protein interactions Immunoassays and protein analysis, insertion of miRNA into adeno-, lenti- and adeno-associated viral vectors and preparation of viruses for transfection in cultured cells and for in vivo use. The signaling molecules studied by ELISA, in vitro kinase assay and Proteomics include, RasGTPas, ERK1/2, MEK, Raf, p38MAPK, c-JNK, PI3 kinase, Akt, JAK-STA, Pyk-2, c-Src, Syk and EGF.

Selected Publications:

• Parmentier, J. H, Muthalif, M. M, Saeed, A. E., Malik. K. U. Phospholipase D activation by norepinephrine is mediated by 12(s)-, 15(s)-, and 20-hydroxyeicosatetraenoic acids generated by stimulation of cytosolic phospholipase A2. J Biol Chem. 276: 15704-15711, 2001.
• Muthalif, M. M., Hefner, Y., Canaan, S., Harper, J., Zhou, H., Parmentier, J.H., Aebersold, R.,Gelb, M. H., and Malik, K. U.  Functional interaction of calcium-/calmodulin-dependent proteinkinase II and cytosolic phospholipase A(2). J Biol Chem. 276 :39653-39660, 2001.
• Parmentier, J. H., Smelcer, P., Pavicevic, Z., Basic, E., Idrizovic, A., Estes, A., Malik, K. U. PKC-zeta mediates norepinephrine-induced phospholipase D activation and cell proliferation in VSMC. Hypertension. 41: 794-800, 2003.
• Yaghini, F. A., Zhang, C., Parmentier, J. H, Estes, A. M, Jafari, N., Schaefer, S. A, Malik, K. U. Contribution of arachidonic acid metabolites derived via cytochrome P4504A to angiotensin II-induced neointimal growth. Hypertension. 45: 1182-1197, 2005.
• Li, F. and Malik, K.U. Angiotensin II-induced Akt activation through the epidermal Growth factor receptor in vascular smooth muscle cells is mediated by phospholipid metabolit derived by activation of phospholipase D. Journal of Pharmacology and Experimental Therapeutics 312: 1043-1054, 2005.
• Yaghini, F. A., Zhang C., Parmentier, J. H., Estes, A., Jafari, N., Schaefer, S. A., and Malik, K. U. Contribution of arachidonic acid metabolite(s) derived via cytochrome P450 4A to angiotensin II-induced neointimal growth. Hypertension 45:1182-1187, 2005.
• Li, F., Zhang, C., Schafer, S., Estes, A. and Malik, K.U. AngII-induced neointimal growth in mediated via cPLA2 and PLD2 activated Akt in balloon-injured rat carotid arteries. American Journal of Physiology American Journal of Physiology, Heart Circulation Physiology 289:H2592 2601, 2005.
• Parmentier, J-H., Zhang, C., Estes, A. and Malik, K.U. Essential role of PKC z in normal and angiotensin II-accelerated neointimal growth after balloon angioplasty. American Journal of Physiology. 291: H1602-1613, 2006.
• Yaghini, A., Li, F. and Malik, K.U. Expression and mechanism of Syk activation by angiotensin II and its implication in protein synthesis in rat vascular smooth muscle cells. Journal of Biological Chemistry 282:16878-16890, 2007.
• Lavrentyev, E. N., Estes, A. M. and Malik, K. U. Mechanism of high glucose induced AngII production in rat vascular smooth muscle cells. Circulation Research 101: 455-464, 2007.