FACULTY LIST
 Michael Michalkiewicz, D.V.M., Ph.D.
Associate Professor
Phone: (414) 456-4835
Email: mmichalk@mcw.edu
D.V.M. University of Wroclaw, Poland, 1975
Ph.D. Warsaw University, Poland, 1981
In my lab, we investigate coding and non-coding regions of the genome responsible for complex diseases, including hypertension, diabetes, and renal failure. For these studies we generate transgenic rat models to validate candidate genes and sequence variants identified by a spectrum of genetic and genomics tests (consomic, expression arrays) as being causal factors underlying complex diseases. In a transgenic rescue approach utilizing a long stretch of DNA (BAC), we have validated a novel Gimap5 (Ian5) gene involved in lymphopenia and are now investigating the involvement of this gene product in the pathogenesis of lymphopenia and type 1 diabetes.
To determine the physiological function of a novel neuropeptide Y gene expressed in the autonomic nervous system, we generated transgenic rats that overexpress this gene in the nervous system, and have demonstrated that endogenous neuropeptide Y exerts potent sympatholytic, hypotensive, and anxiolytic functions. Using these transgenic rats, we are now exploring the mechanism of the hypotensive and cardioprotective function of this peptidergic neurotransmitter.
With the aim of increasing the efficiency of transgenic rat production, we applied a novel lentiviral vector technology and generated lentiviral GFP transgenic rat (green rat). Lentitransgenic method is being used now in our laboratory to develop effective siRNA lentivectors for transgenic gene knockdown in the rat.
Recent Publications:
Michalkiewicz M, Zhao G, Jia Z, Michalkiewicz T, Racadio MJ. Central neuropeptide Y signaling ameliorates L-NAME hypertension in the rat through a Y1 receptor mechanism. Hypertension. 2005;45:780-5.
Michalkiewicz M, Michalkiewicz T, Ettinger RA, Rutledge EA, Fuller JM, Moralejo DH, Van Yserloo B, MacMurray AJ, Kwitek AE, Jacob HJ, Lander ES, Lernmark A. Transgenic rescue demonstrates involvement of the Ian5 gene in T cell development in the rat. Physiol Genomics. 2004;19:228-32.
Michalkiewicz M, Knestaut KM, Bytchkova EY, Michalkiewicz T. Response: Hypotension and Reduced Catecholamines in Neuropeptide Y Transgenic Rats. Hypertension. 41:1056-1062, 2003.
Lee EW, Michalkiewicz M, Kitlinska J, Kalezic I, Switalska H, Yoo P, Sangkharat A, Ji H, Li L, Michalkiewicz T, Ljubisavljevic M, Johansson H, Grant DS, Zukowska Z. Neuropeptide Y induces ischemic angiogenesis and restores function of ischemic skeletal muscles. J Clin Invest. 2003 111:1853-62.
Michalkiewicz M, Michalkiewicz T, Kreulen DL, McDougall SJ. Increased blood pressure responses in neuropeptide Y transgenic rats. Am J Physiol Regul Integr Comp Physiol. 2001 281:R417-26.
Thorsell A, Michalkiewicz M, Dumont Y, Quirion R, Caberlotto L, Rimondini R, Mathe AA, Heilig M. Behavioral insensitivity to restraint stress, absent fear suppression of behavior and impaired spatial learning in transgenic rats with hippocampal neuropeptide Y overexpression.
Proc Natl Acad Sci. 2000;97:12852-7.
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