mmmph! that's a bit of work!
mmmph! that's a bit of work!
I am currently working at the Department of Pediatrics at the Yale University in New Haven, CT, as a post-doctoral fellow. I completed my doctoral studies from the Neurochemistry Lab, Department of Psychiatry in Freiburg, Germany. I graduated from the Indian Institute of Technology (IIT), Bombay, in Biotechnology.
Research
My research interests lie in the field of Neurosciences, at the molecular level. At Yale, I am involved in the studies involving white matter formation in the brain, and consequences of stress conditions such as hypoxia, using mouse models and primary cell cultures. As part of my PhD at Freiburg, I was working on the signal transduction mechanisms involved in Neurodegenerative Disorders. A brief summary of my past work -
I have studied and established the apoptotic pathway in human neuroblastoma cell-line SK-N-SH using a relatively new molecule, TaClo, that is generated in vivo through a condensation of the hypnotic chloral hydrate with the biological amine tryptamine. I have shown that TaClo is pro-apoptotic through the formation of reactive oxygen species that result in cytochrome c release, caspase activation and DNA fragmentation. Currently we are looking for the role of nuclear protein kinases and p53 or its homologues in TaClo-induced apoptosis. Also, we are trying to look for any possible neuroprotective strategies that could be applied to this system which, we presume, is a good model to study neuronal apoptosis in relation to neurodegenerative disorders. We are extending our observations to other model systems of interest, like amyloid-induced neuronal apoptosis in Alzheimer's disease.
I have looked into the probable roles where Protein Kinase C (PKC) could be involved in neuroinflammatory or neurodegenerative disorders. In primary astrocytes, I identified the activation of PKC with lipopolysaccharide (LPS), interleukin 1ß or amyloid, which we find detrimental to the downstream regulation of cyclooxygenases and its receptors (EP). I have also identified the down-regulation of PKC by serotonin (5-HT) and adenosine in astrocytoma cells that leads to interleukin 6 synthesis. This methodology has been extended to other models in the lab where PKC was identified as a candidate enzyme whose inhibition could be neuroprotective; for example, inhibition of substance P induced interleukin 6 synthesis by sodium valproate in astrocytoma cells, or inhibition of LPS-induced cytokine synthesis in human monocytes by the plant extract Harpagophytum.
Other transduction enzymes I have been studying involve phospholipases (PLA2) and sphingomyelinases (SMase) for their involvement in neuroinflammatory pathways.
I am studying the central role of microglia in neuroinflammation that become activated in various neurodegenerative disorders like Alzheimer's or Parkinson's; using particular emphasis on inflammatory cytokines such as prostaglandin's and molecules such as nitric oxide and their regulatory enzymes cyclo-oxygenases (COX 1,2) and nitric oxide synthetase (iNOS) as well as upstream (PLA2, SMase, PKC, ERK, p38) and downstream (proteasomes, NF-kB) targets. We are studying this system through insults like LPS or radiation and neuroprotective strategies using growth factors like NGF or herbal extracts like Hypericum extracts.