Department of Life Sciences
Old Westbury Campus
Theobald Hall, room 425
Ph.D. Molecular Pharmacology, Division of Biological Sciences, Albert Einstein College of Medicine, Bronx, New York, USA
M.S. Molecular Pharmacology, Division of Biological Sciences, Albert Einstein College of Medicine, Bronx, New York, USA
At the Clinical Research Centre in Harrow, England I was involved in the purification of thyroxine binding globulin and the development of radioimmunoassay for thyroid hormones.
In the laboratory of Dr Stanley Ulick at the Veterans Administration Hospital, NY, USA, I was involved in the discovery of a new steroid (18-oxocortisol) and in its synthesis and purification. I was also interested in identifying new steroids that would antagonize of the actions of aldosterone.
As a Research Associate at Albert Einstein College of Medicine, Bronx. New York, USA I cloned two protein kinase C (PKC) isoforms and a novel protein Kinase (PKL) from, Caenorhabditis elegans. I discovered that both of the C.elegans genes corresponding to PKC-1 and PKC-2 have multiple promoters.
Protein Kinase C substrates and pathways:
I am studying protein phosphorylation and signal transduction. The protein kinase C (PKC) family of enzymes regulates many processes, including growth, secretion, differentiation, and neuronal function by phosphorylating downstream targets such as ion channels and transcription factors. Neurotransmitters, hormones and growth factors bind G-protein-coupled receptors or receptor tyrosine kinases leading to the stimulation of phospholipases. Phospholipase C generates diacylglycerol (DAG) and together with Ca2+ activates classical (c) PKCs.. Aberrant activation of PKC is linked to tumor promotion. A number of diseases are associated with mutations within PKC genes or misexpression of PKC, for example, ataxia in humans, heart failure in mouse and Parkinsonian syndrome in rat. A great deal is known regarding structures, activation mechanisms and substrates, however information about in vivo regulation, downstream effectors and the physiological roles of individual PKC isoforms is more limited.
I am using a genetic, proteomic and biochemical approach to identify upstream and downstream components of the PKC pathway. I cloned two protein kinase C (PKC) isoforms and a novel protein Kinase (PKL) from the free living nematode worm, Caenorhabditis elegans. Most biological pathways and genes that are found in humans are present in C. elegans, for example the aging and apoptosis (cell death) pathways were discovered in this worm. I have discovered that the only classical isoform in C.elegans, PKC-2 is essential for normal thermotactic behavioral responses in the worm. My studies have allowed me to determine that PKC-2 is regulated by a cyclic nucleotide gated calcium channel. Using Differential gel electrophotesis (DIGE), I have identified proteins that have shifted mobilities in nematodes that over express PKC-2, indicating alterations in phosphorylation or other post-translational modifications. Characterization of these potential PKC-2 substrates is underway.
My studies may lead to the development of new therapeutic agents. My research involves biochemical, microbiological and molecular biological techniques (e.g. cloning, PCR, protein expression), cell biology, and genetics.