Dr. Srinivasa Karnam
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Contact Information
Department of Physiology and Biophysics Virginia Commonwealth University P.O. Box 980551 Richmond, Virginia 23298-0551 Tel: 804-828-0029 Fax: 804-828-7382 email: skarnam@vcu.edu |
S. Murthy Karnam (publishing as Karnam S. Murthy) received his undergraduate degree in Biology in 1977, a Masters degree in Zoology in 1979 and Ph.D. degree in Molecular Physiology in 1983 from Sri Venkateswara University India. After completing his post-doctoral training in the laboratories of Dr. William Benjamin at the State University of New York at Stony Brook and Dr. Gabriel Makhlouf at the Virginia Commonwealth University, he became a faculty member in the Department of Physiology in 1992.
Research
Our work focuses on understanding the molecular basis of signaling mechanisms mediated by G protein-coupled receptors in gastrointestinal smooth muscle. G protein-mediated signaling cascades are key regulators of many physiological processes, including processes of development, differentiation, and smooth muscle activity. In the gastrointestinal tract both excitatory and inhibitory neurotransmitters modulate muscle tone by activation of such G protein cascades. Much of our work on the role of neurotransmitters has focused on how these transmitters affect the contraction and relaxations of smooth muscle that are responsible for peristaltic activity of the gut. We have used the both physiological and molecular approaches extensively to identify the receptors and the signaling pathways coupled to function using isolated smooth muscle myocytes. In some cases G protein-coupled receptors have been cloned and expressed in heterologous expression systems to identify their signaling pathways and to further explore the molecular mechanisms underlying regulation of G protein signaling.
Visceral smooth muscle contraction and relaxation are mediated by phosphorylation and dephosphorylation of the 20-kDa contractile protein myosin light chain (MLC20). Levels of MLC20 phosphorylation are regulated by kinases and phosphatases, which, in turn, are regulated by intracellular signaling molecules such as RhoA, RhoA-kinase, MYPT1 (regulatory subunit of phosphatase) and CPI-17 (endogenous inhibitor of phosphatase) via both Ca2+-dependent and -independent mechanisms. The involvement of various signaling pathways is both receptor- and tissue-specific. Our studies using both biochemical and molecular biological approaches are directed to identify the specific signaling pathways initiated by both excitatory and inhibitory neurotransmitters. Identifying the intracellular mechanisms involved in smooth muscle contraction and relaxation are pertinent to understand the normal function and some of the changes associated with motility disorders.
Our research is also focused on examining the changes in the signal transduction pathways leading to altered motility during inflammation. Studies include identification of changes in the expression and activity of key signaling molecules by both transcriptional and post-translational mechanism. The long-term goal is to uncover novel cytokine targets that regulate G protein function and altered response of the smooth muscle during inflammation.
The collegial environment within our Department has allowed members of our laboratory to develop ongoing collaborations with other faculty within our Department and other Departments at the Virginia Commonwealth University. These collaborations have led to a multifaceted approach aiming to understand the signaling mechanism that control smooth muscle function during peristalsis in health and disease.
We currently use a large number of molecular and cellular techniques and attempt to exploit new methods as they are developed. Some of the techniques we frequently employ include isolation and culture of smooth muscle cells, scanning micrometry for measurement of muscle cell length, radioligand binding assays, ELISA, mRNA and DNA isolation, cloning; quantitative polymerase chain reaction; northern, southern, and western analysis; DNA sequencing; bacterial transformations; transfections.
Our work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases for over 20 years.
Teaching
My teaching activities include graduate, medical, dental and pharmacy students. I lecture on selected topics of muscle and gastrointestinal physiology for first year Medical, Dentistry and Pharmacy students. In addition, I lecture on Cell Signaling in several advanced physiology courses. I also actively participate in the research training of undergraduate, graduate and medical students, as well as post-doctoral research fellows. I am a mentor in several NIH training grants and the MD/PhD training program.
Selected Publications
Original Work
Zhou, H., Huang, J., and Murthy, K.S. Molecular cloning and functional expression of a VIP-specific receptor Am. J. Physiol. Gastrointest. Liver Physiol. 291: G728-G734, 2006. PubMed
Hu, W., Mahavadi, S., Huang, J., Li, F., and Murthy, K.S. Characterization of S1P1 and S1P2 receptor function in smooth muscle by receptor silencing and receptor protection. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G605-G610, 2006. PubMed
Huang, J., Zhou, H., Mahavadi, S., Sriwai, W., and Murthy, K.S. Inhibition of Gaq dependent PLC-b1 activity by PKG and PKA is mediated by phosphorylation of RGS4 and GRK2. Am. J. Physiol. Cell Physiol. 292: C200-C208, 2007. PubMed
Huang, J. Mahavadi, S., Grider, J.R., and Murthy, K.S. Cross-regulation of VPAC2 receptor desensitization by m3 receptors via PKC-mediated phosphorylation of RKIP and inhibition of GRK2. Am. J. Physiol. Gastrointest. Liver Physiol. G867-G874, 2007. PubMed
Sriwai, W., Zhou, H., and Murthy, K.S. Gq-dependent signaling by lysophosphatidic acid receptor LPA3 in gastric smooth muscle: reciprocal regulation of MYPT1 phosphorylation by Rho kinase and cAMP-independent PKA. Biochem. J. 2008; [Epub ahead of print]. PubMed
Reviews
Murthy, K.S. Signaling for contraction and relaxation in signaling of the gut. Annu. Rev. Physiol. 68: 345-374, 2006. PubMed
Additional publications are linked here