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Nikolai N. Modyanov Ph.D., D.Sc, Professor in the Department of Physiology and Pharmacology
Dr. Modyanov received his PhD in from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry , Moscow, Russia in 1973, where he subsequently was doing research for 25 years. Professor Modyanov was a Head of Laboratory of Membrane Biochemistry since1986. In 1994 he joined the University of Toledo College of Medicine as Professor of Pharmacology.
For more than 30 years Dr.Modyanov's research was focused on the molecular aspects of ion transport across biological membranes, and primarily on the structure-function relationship of the ion-transporting ATPases that are receptors for cardiotonic drugs (Na,K-ATPase) and antiulcer drugs (H,K-ATPase).
New direction of his research resulted in discovery of the unique BetaM proteins encoded by ATP1B4 genes, members of X,K-ATPase gene family. He determined that ATP1B4 genes represent a rare instance of orthologous vertebrate gene co-option that created fundamental changes in the physiological roles and functional properties of the encoded proteins. In lower vertebrates BetaM is a subunit of Na,K-ATPase. In placental mammals BetaM-proteins lost their ancestral functions and acquired entirely new functions as proteins in the inner nuclear membrane of heart and skeletal muscle, which regulate gene expression and signal transduction acting specifically during a critical period of perinatal development and adult muscle regeneration.
These findings clearly indicate that placental mammals should have a hitherto unknown physiologically important necessity, which did require evolutionary forces to trigger co-option of the X-chromosome gene ATP1B4 and fundamental changes in the functional properties of the BetaM proteins.
To better understand the physiological role of the mammalian BetaM, Dr.Modyanov developed Atp1b4 knockout mouse model and determined that BetaM deficiency sharply decreased level of expression of a major myogenic regulatory factor MyoD and slow down mouse general body development and growth. Moreover, the survival rate of Atp1b4-/Y males and homozygous Atp1b4-/- females is significantly lower than that of male wild type and heterozygous female littermates, respectively.
Most importantly, Atp1b4 knockout males, which survived to adulthood, upon feeding by a high-fat diet showed far less weight gain, are resistant to diet-induced obesity, exhibit enhanced insulin sensitivity and improved glucose tolerance compared with wild type littermates. Studies on the molecular basis of these beneficial effects of BetaM ablation on dietary fat metabolism are now in progress.
Dr.Modyanov has authored 144 peer-reviewed articles. His current research is supported by CeDER.