Center for Cell Signaling
phone 713.500.2481; fax 713.500.2498
Ferid
Murad, M.D., Ph.D.
Professor & Director
Ka Bian, M.D., Ph.D. - Assistant Professor
Nathan S. Bryan, Ph.D. - Assistant Professor
Alexander Y. Kots, Ph.D. - Instructor
Emil Martin, Ph.D. - Assistant Professor
Kalpana Mujoo, Ph.D. - Assistant Professor
Iraida Sharina, Ph.D. - Research Instructor
Since Murad’s early research training with Nobel Laureate Earl Sutherland and Theodore Rall with adenylyl cyclase and cyclic AMP, he has been interested and focused on cellular signaling pathways utilizing second messenger systems. He has contributed to molecular mechanisms of hormone and drug action extensively in the areas of adenylyl and guanylyl cyclases and the cyclic nucleotides cyclic AMP and cyclic GMP. His interests with cyclic GMP led him to discover the early biological effects of nitric oxide. Since his first publications with NO in 1977 and 1978, there have been more than 80,000 publications in the field of NO research. His research team has contributed in many of these areas.
His current research focus remains in the area of NO and cyclic GMP. His laboratory has been the first to purify and characterize most of the isoforms of guanylyl cyclase and nitric oxide synthase and clone the cDNA’s for many of these enzymes. His laboratory was the first to determine that soluble guanylyl cyclase is the NO receptor and is a hetero dimer and that particulate guanylyl cyclases are receptors for various peptides and toxins. They have determined the genomic structure and organization for the soluble guanylyl cyclase alpha and beta subunits, chromosomal localization; the promoters, and alternate splicing isoforms. They have developed a conditional sGC knock out mouse model and some of the features of the phenotype. They have developed numerous mutants of sGC in order to determine the mechanism of NO activation and to serve as molecular targets to identify novel activators and inhibitors of the enzyme. These studies have led to spectral studies (visible, UV, infrared, Raman and EPR) of large quantities of human recombinant enzyme. Yeast 2-hybrid screening has resulted in a large library of positive clones with proteins that interact with either the alpha or beta subunits of sGC. The significance of most of these proteins is currently under investigation.
Novel inhibitors of cyclases that they discovered are being examined for treating bacterial toxin diarrheas and inflammatory bowel disease. Topical NO donors (prodrugs) have been examined in burn and wound healing models in mice and rats. This work has led to a series of cosmetic products that are on the market in Asia.
A major program currently in the laboratory is to examine the role of NO and cyclic GMP in mouse and human embryonic stem cell differentiation and cancer cell lines. Novel biomarkers for use in cancer diagnosis and therapy are also being examined.
A round worm factor from Trichinella spiralis has been discovered in their laboratory that suppresses NOS-2 expression in tissues as a novel approach to inflammatory disorders.
The cardiovascular effects of dietary nitrite are also being examined in the Center. We believe that nitrite can function as a precursor or prodrug to be converted to NO and activate sGC and/or post traditionally modify proteins.
We have identified numerous proteins that are nitrated on their tyrosyl residues resulting in altered structural or catalytic activity and have established that reactive oxygen species (ROS) and redox pathways participate in these processes.
The Murad Research Center in Shanghai since 2003 has been examining selected herbal extracts (Traditional Chinese Medicine or TCM’s) for their mechanisms of action on vascular, platelet and cell culture preparations that may entail the NO/cGMP signaling systems. A number of extracts have been identified that relax vascular preparations in an endothelial dependent or independent manner. This program is located in the Shanghai University of TCM and is supported by funding from the University and the Chinese Government. At some point some of the novel and promising samples will be tested in the IMM on various biochemical parameters. The Houston program is supported with multiple grants from the NIH, the Defense Department, NASA, several foundations and the University of Texas.