Iraida Sharina, Ph.D.
Research Instructor;
Center for Cell Signaling
phone 713.500.2480;
fax 713.500.2447
Iraida.G.Sharina@uth.tmc.edu
The main research interests of Dr. Sharina are directed towards unraveling the multiple physiological oles of NO-dependent cGMP signaling.
Dr. Sharina earned her Masters Degree in Organic Chemistry and Chemical Engineering from the Department of Organic Chemistry of Moscow Institute of Fine Chemical Technology. She received her Ph. D in Molecular Biology from the Institute of Molecular Genetics of Russian Academy of Science in Moscow, where she was the recipient of Soros Foundation Stipend for Young Investigators. In 1995 Dr. Sharina pursued her post-doctoral training at Albert Einstein College of Medicine. There, in the laboratory of the Director of AECOM Cancer Research Center Dr. David I. Goldman she was conducting structure functional studies of Reduced Folate Carrier, the major determinant of anti-folate resistance in cancer. In 1999 she joined the laboratory of Dr. Ferid Murad in the Department of Integrative Biology and Pharmacology at the University of Texas Medical School at Houston. There she received the Jump Start Award for Young Investigators and was promoted to Instructor position in 2002. In June of 2006 Dr. Sharina joined the Institute of Molecular Medicine as Instructor in the Center for Cell Signaling. She is also a faculty member of the Department of Integrative Biology and Pharmacology at the Medical School.
Dr. Sharina’s current research efforts are directed towards a better understanding of the multiple physiological roles of heterodimeric Soluble Guanylyl Cyclase (sGC). sGC is the main receptor for Nitric Oxide (NO), a signaling molecule with numerous physiological functions, including relaxation of vascular smooth muscle, inhibition of platelet aggregation, neurotranmission and modulation of cellular differentiation. While the role for sGC in the vasculature was first identified 20 years ago, understanding of the physiological significance of NO-sGC-cGMP signaling remains incomplete. To unravel the function of sGC in various tissues Dr. Sharina developed a conditional sGC gene targeted mouse. This approach allows to overcome the problems associated with the complexity of the nitric oxide/sGC signaling (lack of selective sGC inhibitors; redundancy of several sGC isoforms; cGMP-dependent and -independent actions of NO). Studies utilizing this unique model to uncover sGC function in myocardial and regenerative tissues are currently underway.
Dr. Sharina also investigates transcriptional and post-transcriptional mechanisms of sGC expression. sGC expression is subject to hormonal and cytokine regulation. Changes in sGC expressional level and activity influence cardiovascular homeostasis, hypertension and is changed during bacterimia, septic shock or cytokine-dependent treatment of cancer. Analysis of mechanisms and identification of regulators that control and coordinate the expression of different sGC subunits in the normal and pathological conditions is the main goal of this study. Recently, Dr. Sharina isolated new splice variants of one of the major subunits sGC. Functional studies demonstrate that these splice isoforms are not only differentially expressed in human tissues and embryonic stem cells, but also directly influence the activity and possibly the function of sGC enzyme.
Selected publications:
Nedospasov A.A., Sharina I.G. " Synthesis of N(S)-alcoxyethyl-substituted aminonaphthalensulfonamides by opening the azyridene cycle." Synthetic Letters 1993, 8, 661-662
Rongbao Zhao, Sharina I.G. and I. David Goldman, “Pattern of mutations that results in loss of reduced folate carrier function under antifolate selective pressure augmented by chemical mutagenesis.” Mol Pharmacol. 1999, 56(1):68-76
Sharina I.G., Krumenacker J.S., Martin E. and Murad F., “Genomic organization of alpha1 and beta1 subunits of the mammalian soluble guaylyl cyclase genes” Proc Natl Acad Sci U S A, 2000, 97(20):10878-10883
Iraida G. Sharina, Rongbao Zhao, Solomon Babani, Yanghua Wang and I. David Goldman, “Mutational analysis of the functional role of conserved arginine and lysine residues in transmembrane domains of murine reduced folate carrier”. Mol Pharmacol, 2001, 59(5):1022-1028
Iraida G. Sharina, Rongbao Zhao, Yanghua Wang, Solomon Babani and I. David Goldman, “The role of the C-terminus and the long cytoplasmic loop in reduced folate carrier function”. Biochem. Pharm, 2002, 63:1717-1724
Martin E, Sharina I, Kots A, Murad F. A constitutively activated mutant of human soluble guanylyl cyclase (sGC): implication for the mechanism of sGC activation. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9208-13.
Sharina IG, Martin E, Thomas A, Uray KL, Murad F. CCAAT-binding factor regulates expression of the beta1 subunit of soluble guanylyl cyclase gene in the BE2 human neuroblastoma cell line. Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11523-8.
Martin E., Sharina I, Seminara A.R., Krumenaker J. and Murad F. Nitric oxide cell signaling mediated by GMP. In Nitric Oxide Cell signaling and Gene Expression. (2005).
Patents:
Nedospasov A.A. and Sharina I.G. (1993) "Substituted aminonaphthalensulfon-amide as intermediate products in synthesis of detection groups used for enzyme analysis and methods of their synthesis". Russian patent N 4949863/04.
Nedospasov A.A. and Sharina I.G. (1993) " Aminonaphthalensulfonamide as detection groups for chomatographic analysis of enzymes and methods of their synthesis." Russian patent N 4949862/04.
Nedospasov A.A. and Sharina I.G. (1993) "Substituted naphthalen(dimethilen)-sulfonamides as an intermediate product in synthesis of naphthalensulfonamide with an alcoxiethyl radical in sulfonamide group and methods of their synthesis”. Russian patent N 4950036/04.
Nedospasov A.A. and Sharina I.G. (1993) "5-arginilaminonaphthalen -1-(alcoxiethyl) sulfonamide as a substrate for ANSA-analysis of enzymes with proteolytic activity". Russian patent N 2000297.
Unated States Patent UTSH:252US (2000): Ferid Murad, Iraida Sharina, J.S. Krumenaker and E. Martin. “Genomic organization of mouse and human sGC”.