Research Interests: Signal transduction in relation to gene regulation in infectious agents, functional genomics, reversible protein phosphorylation, structure-function analysis of protein kinases, phosphatases, and their physiological substrates. The main focus of our research is to study host-pathogen interaction using a combination of classical biochemistry and modern molecular biology. The host cells are of human origin, whereas the pathogens cover three major kinds: viral, bacterial, and protozoal. We have also pioneered the use of RNA interference as a major tool in this area of research. The viral pathogens include negative-strand RNA viruses with special emphasis on respiratory syncytial virus (RSV), a major pediatric pathogen, causing "croup" in little children. Our studies have helped define the transcription complex of the virus, and established an essential role of the viral phosphoprotein (P) in the RNA-dependent RNA polymerase activity. We have also shown that cellular actin is essential for RSV transcription. Recent studies in the lab focus on: (a) the role of actin and other cytoskeletal proteins (such as profilin) in RSV life cycle and host-RSV signaling; (b) the mechanism of regulation of apoptosis in RSV-infected lung cells; and (c) the mechanism of activation of NF-kappa B, a host transcription factor, by RSV. In addition, we investigate the hypothesis that RSV also infects the human eye, causing allergy eye, and eventually gaining entry into the respiratory tract. We have initiated studies on a clinically important bacterium, Porphyromonas gingivalis, which causes periodontal disease worldwide. The various aspects of infection of gum epithelium and fibroblasts with P. gingivalis are being pursued. The third major interest is to study the fundamental aspects of protein kinases and phosphatases in Apicomplexan parasites, exemplified by Plasmodium falciparum and Toxoplasma gondii, protozoan parasites that cause malaria and toxoplasmosis, respectively. We have discovered a number of kinases and phosphatases in the malarial parasite that were found to be critical regulators of parasitic development and physiology. Further studies of these enzymes and their genes, and identification of their physiological function would provide necessary insights into the mechanisms of signal transduction in this eukaryotic protozoan. Current research is supported mainly by the National Institutes of Health (www.nih.gov). Representative Publications: Adams B, Musiyenko A, Kumar R, Barik S. A novel class of dual-family immunophilins. J Biol Chem. 2005; [Epub ahead of print] Kumar R, Adams B, Musiyenko A, Shulyayeva O, Barik S. The
FK506-binding protein of the malaria parasite, Plasmodium falciparum, is
a FK506-sensitive chaperone
with FK506-independent calcineurin-inhibitory activity. Mol Biochem Parasitol.
2005;141(2):163-73. Bitko V, Musiyenko A, Shulyayeva O, Barik S. Inhibition of respiratory viruses by nasally administered siRNA. Nat Med. 2005;11(1):50-5. Barik S. Development of gene-specific double-stranded RNA drugs. Ann Med. 2004;36(7):540-51. Barik S. When proteome meets genome: the alpha helix and the beta strand of proteins are eschewed by mRNA splice junctions and may define the minimal indivisible modules of protein architecture. J Biosci. 2004;29(3):261-73. Bitko V, Garmon NE, Cao T, Estrada B, Oakes JE, Lausch RN, Barik S. Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection. BMC Microbiol. 2004;4(1):28. Kumar R, Musiyenko A, Oldenburg A, Adams B, Barik S. Post-translational generation of constitutively active cores from larger phosphatases in the malaria parasite, Plasmodium falciparum: implications for proteomics. BMC Mol Biol. 2004;5(1):6. Maggon K, Barik S. New drugs and treatment for respiratory syncytial virus. Rev Med Virol. 2004;14(3):149-68. Barik S. Control of nonsegmented negative-strand RNA virus replication by siRNA. Virus Res. 2004;102(1):27-35. Kumar R, Musiyenko A, Cioffi E, Oldenburg A, Adams B, Bitko V, Krishna SS, Barik S. A zinc-binding dual-specificity YVH1 phosphatase in the malaria parasite, Plasmodium falciparum, and its interaction with the nuclear protein, pescadillo. Mol Biochem Parasitol. 2004;133(2):297-310. Kumar R, Musiyenko A, Barik S. The heat shock protein 90 of Plasmodium falciparum and antimalarial activity of its inhibitor, geldanamycin. Malar J. 2003;2(1):30. Bitko V, Oldenburg A, Garmon NE, Barik S. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus. BMC Microbiol. 2003;3(1):9. Kumar R, Adams B, Oldenburg A, Musiyenko A, Barik S. Characterisation
and expression of a PP1 serine/threonine protein phosphatase (PfPP1) from
the malaria
parasite, Plasmodium falciparum: demonstration of its essential role using
RNA interference. Malar J. 2002;1(1):5. Dobson S, Kar B, Kumar R, Adams B, Barik S. A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum. BMC Microbiol. 2001;1(1):31. Bitko V, Barik S. An endoplasmic reticulum-specific stress-activated caspase (caspase-12) is implicated in the apoptosis of A549 epithelial cells by respiratory syncytial virus. J Cell Biochem. 2001;80(3):441-54. Burke E, Mahoney NM, Almo SC, Barik S. Profilin is required for optimal actin-dependent transcription of respiratory syncytial virus genome RNA. J Virol. 2000 Jan;74(2):669-75.
 
The URL for this page is http://southmed.usouthal.edu/com/biochem/barik.html
|
