The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Internal Medicine-Cardiology
In one line of studies we investigate the molecular mechanisms responsible for the conversion of exogenous nitric oxide signal into intracellular messenger molecule cGMP. This conversion is performed by NO receptor, a cytosolic soluble guanylyl cyclase (sGC). Using recombinantly expressed human sGC we investigate the molecular events leading to sGC by nitric oxide. In addition to NO-dependent regulation, we also explore alternative NO-independent methods of sGC regulation, including regulation by cellular thiols, nucleotides, interacting proteins and protein kinases. Mechanisms of action of pharmacological agents known to modulate sGC function in cells and whole organisms are investigated. We have recently identified a number of naturally occurring compounds which activate sGC not only in vitro, but also regulate sGC function in vivo, e.g. induce sGC-mediated relaxation of vascular smooth muscles, regulation of blood pressure. We are currently exploring this as a potential method of NO-independent modulation of sGC physiological function, especially in cardiovascular health.
In another line of investigation we study the regulation of gene transcription by cGMP. Microarray gene expression profiles were employed to identify genes responsive to variation in intracellular cGMP concentrations. Of particular interest are the genes regulated independently on cGMP-dependent protein kinase.
A tutorial in my laboratory would provide experience with various techniques in biochemistry, cell biology and pharmacology. The laboratory make extensive use of systems of recombinant protein expression (insect cell, bacteria, mammalian cell lines), protein purification, enzymology, molecular biological techniques (e.g. cloning, PCR, RT-PCR, RNA isolation, q-RT-PCR). A tutorial would provide intensive exposure to these methods and techniques as well as to the biology of NO/cGMP signaling pathway.
Education & Training
Ph.D. - Russian Academy of Sciences/Columbia University - 1993