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Faculty Detail    
Name NATALIA KEDISHVILI
Professor
 
Campus Address KAUL 440B Zip 0024
Phone 205-996-4023
E-mail nkedishvili@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 

Biographical Sketch 
Natalia Y. Kedishvili, Professor of Biochemistry and Molecular Genetics, received her M.S. degree in Biochemistry in 1982, and a Ph.D. degree in Biochemistry in 1987 from the Lomonosov’s Moscow State University, Russia. After completing her postdoctoral fellowship at Indiana University School of Medicine, she was recruited by the University of Missouri-Kansas City, where she developed a research program in retinoid and steroid metabolism. Dr. Kedishvili joined the UAB faculty in 2004.

Research/Clinical Interest
Title
Discovery and characterization of novel enzymes that regulate the conversion of vitamin A to bioactive retinoic acid
Description
Retinoic acid (RA) is a biologically potent small lipophilic molecule derived from vitamin A (retinol). RA regulates the expression of over 530 different genes in various types of cells and tissues through binding to the RAR (α, β and γ) and PPAR (β/δ) nuclear hormone receptors, which act as heterodimers with RXR nuclear transcription factors. Because of its ability to activate or repress gene transcription, RA plays an important role in differentiation and development of fetal and adult tissues; stem cell differentiation; apoptosis; reproductive functions; immune response; and regulation of energy metabolism. Although the biological functions of RA are well characterized, the exact enzymes involved in the biosynthesis of RA from vitamin A or beta-carotene and the mechanisms that regulate the levels of retinoic acid have not yet been fully defined. The major goal of our laboratory is to discover and characterize the missing enzymes that are responsible for RA biosynthesis and regulation of its intracellular levels. To achieve our goals, we employ a wide variety of approaches and techniques such as recombinant protein expression and purification; assays of protein-protein interaction; in vitro assays of enzyme activity and analysis of reaction products using spectrophotometry, high-pressure liquid chromatography and thin-layer chromatography; stable and transient expression of enzymes in eukaryotic, bacterial and insect cell cultures; silencing of individual human genes using RNA interference; and gene knockout animal models.

Selected Publications 
Publication PUBMEDID
Adams MK, Belyaeva OV, Wu L, Kedishvili NY. The Retinaldehyde Reductase Activity of DHRS3 Is Reciprocally Activated by Retinol Dehydrogenase 10 to Control Retinoid Homeostasis. J Biol Chem. 2014 May 23;289(21):14868-80. doi: 10.1074/jbc.M114.552257. Epub 2014 Apr 14.
 
 
Lee, S.A., Belyaeva, O.V., Popov, I.K., Kedishvili, N.Y. Overproduction of bioactive retinoic acid in cells expressing disease-associated mutants of retinol dehydrogenase 12. J. Biol. Chem. 282, 35621-35628, 2007.   
Belyaeva, O.V., Johnson, M.P., Kedishvili, N.Y. Kinetic analysis of human enzyme RDH10 defines the characteristics of a physiologically relevant retinol dehydrogenase. J. Biol. Chem. 283, 20299-20308, 2008, PMCID: PMC2459273.   
Lee, S.A., Belyaeva, O.V., Kedishvili, N.Y. Disease-associated variants of microsomal retinol dehydrogenase 12 (RDH12) are degraded at mutant-specific rates. FEBS Lett. 584, 507-510, 2010.   
Lee, S.A., Belyaeva, O.V., Kedishvili, N.Y. Evidence that proteosome inhibitors and chemical chaperones can rescue the activity of retinol dehydrogenase 12 mutant T49M. Chem. Biol. Interact. 191, 55-59, 2011.   
Lee, S.A., Belyaeva, O.V., Wu, L., Kedishvili, N.Y. Retinol dehydrogenase 10 but not retinol/sterol dehydrogenase(s) regulates the expression of retinoic acid-responsive genes in human transgenic skin raft culture. J. Biol. Chem. 286, 13550-13560, 2011.   
Belyaeva OV, Lee SA, Adams MK, Chang C, Kedishvili NY. Short chain dehydrogenase/reductase rdhe2 is a novel retinol dehydrogenase essential for frog embryonic development. J Biol Chem. 2012 Mar 16;287(12):9061-71. doi: 10.1074/jbc.M111.336727. Epub 2012 Jan 30.
 
 

Keywords
vitamin A, retinoic acid, oxidoreductases, development, differentiation