Member SpotlightsCardiovascular Studies: The Role of Intracellular Calcium in Hypoxic Pulmonary Vasoconstriction (HPV) Rakesh Rathore, Ph.D. One of the newest members to The Science Advisory Board.  Rakesh Rathore, Ph.D., is a Research Associate at Albany Medical Center's Department of Cardiovascular Sciences in the US. Rathore draws from a highly varied background of experiences. While completing his Masters degree in India, he worked at the Cancer Hospital & Research Institute. As a Ph.D student at G.B. Pant University of Agriculture & Technology, he worked with, "the molecular biology of legume plants, especially the development of legume transgenics for insect resistance and nutritional quality improvement." Rathore received the prestigious Council of Scientific and Industrial Research (CSIR) fellowship and also worked at the National Research Center on Plant Biotechnology, New Delhi, during his Ph.D. His doctoral work was presented at the International Crop Science Congress, Germany, and the International Congress of Plant Molecular Biology, Canada. Rathore's academic background in molecular cell biology and biochemistry would later support his interest in a specific molecular area: calcium channels and signaling in smooth muscle. Current society memberships include the American Heart Association/American Stroke Association, American Biophysical Society, and American Association for the Advancement of Science. Describe the work you conducted in molecular research prior to joining Albany Medical Center. I received a Postdoctoral fellowship from Carl Trygger Foundation, Sweden to join the Membrane Protein group (Prof. Ake Strid/Prof. Pal Nyren) at Gothenburg University, Sweden. My project was focused on the membrane protein pyrophosphatase, and I was able to use genetic engineering to construct a fusion protein between the highly hydrophobic pyrophosphatase for the development of pH sensors inside and outside the membrane. Through that work experience, I learned many of the intricacies of membrane protein biochemistry and molecular biology. I also got incredible opportunities to present my work in various conferences and training/courses, including the Department of Bioscience, Karolinska Institute, Stockholm, Sweden; International Centre for Genetic Engineering & Biotechnology (ICGEB), Trieste, Italy, and the European Science Foundation at Estonian Bio Center. Describe your current occupation and the research focus of your lab. Currently, I am working as a Research Associate in the Department of Cardiovascular Sciences at Albany Medical Center, NY, in the field of molecular cell biology & biochemistry, specifically calcium signaling. I am also involved in teaching a Advanced System Physiology/Smooth Muscle Lab course to graduate students from Rensselaer Polytechnic Institute, Troy, NY. Due to my interest in smooth muscle cell signal transduction (a rapidly progressing field) and to further extend my protein biochemistry and molecular biology expertise, I joined Prof. Wang's research lab. [This lab] is focused on calcium signaling in smooth muscle, and is at the Department of Cardiovascular Sciences, Albany Medical Center. Our lab is focused on Ca2+ signaling, which is generated and controlled by intracellular Ca2+ release channels and plasmalemmal Ca2+-permeable channels. Our main research interests are to define: 1) the cellular and molecular mechanisms that regulate intracellular Ca2+ release and plasmalemmal Ca2+ influx, 2) the roles of intracellular Ca2+ as a signal in cellular responses, and 3) the cellular and molecular processes coupling Ca2+ signaling to Ca2+-activated ion channels, particularly in smooth muscle cells under physiological and pathological conditions. We pursue these goals using laser scanning confocal microscopes, wide-field calcium imaging, patch clamps, biochemical, molecular, and genetic (gene overexpression and knockout) approaches. My current projects are mainly focused on the role of intracellular Ca2+ release in the development of hypoxia-induced pulmonary vasoconstriction and associated pulmonary hypertension in smooth muscle cells. In these research projects, we attempt to determine: 1) how hypoxia induces Ca2+ release from intracellular stores and 2) what primary oxygen sensors and key signal transducing elements are in hypoxic Ca2+ release. Specifically, we are focused on the roles of ryanodine receptors, inositol triphosphate receptors, FK506 binding protein 12 & 12.6, mitochondria, NADPH oxidase, reactive oxygen species, redox potential and protein kinase C, in hypoxic Ca2+ release in pulmonary artery myocytes. What progress have you made in your investigations? I successfully demonstrated the biochemical role of PKC-epsilon in HPV, which is activated by mitochondria-derived reactive oxygen species in pulmonary arteries, and also determined the role of Type-3 Ryanodine Receptor in mediating hypoxia and contraction in pulmonary artery smooth muscles. I am also working on NADPH oxidase and other signaling molecules to understand further the complicated calcium signaling pathways in smooth muscle cells. Are you studying calcium in areas other than its relation to hypoxia? My other research interests are focused on the regulation and functions of calcium influx and calcium release in cerebral and airway smooth muscles. We are investigating the role of ion channels in type-1 diabetic cerebral artery smooth muscle cells and role of intracellular calcium release and sensitivity in airway hyper-responsiveness. Initially, your research studies involved the molecular biology of plants, and this changed to the molecular biology of smooth muscle. What are your reasons for pursuing calcium signaling? Calcium signaling research is one of the most important cellular signaling mechanisms implicated in the regulation of biological function. I believe that the findings from our work will not only extend our understanding of cellular and molecular mechanisms underlying the physiological functions of vascular and airway smooth muscles, but also the development of hypertension, diabetes, asthma & other diseases, and it may bring new powerful therapies to treat these diseases. What are your thoughts on the progress of your career thus far and where do you see yourself in the future? So far, my career has been, more or less, as planned. I am very satisfied with my current work as it may bring a better understanding of cellular and molecular mechanisms for the development of hypertension, diabetes, and asthma. As far as my career success is concerned, what the future brings is still very open and largely depends on my future best efforts in the scientific journey. I would like to get grants and a faculty position. If possible I will try to collaborate/work together with industry for technology development & make a few novel discoveries along the way of my scientific career. To discuss calcium signaling research and other topics with fellow Science Adivisory Board members, please visit our community forum. Rathore's personal home page with scientific links can be found at www.rakeshrathore.com. The following are publications and presentations authored and co-authored by Rathore that are relevant to this Member Spotlight. Publications Ling Dong, Yun-Min Zheng,Dee Van Riper, Rakesh Rathore,Qing-Hua Liu, Harold A. Singer, Yong-Xiao Wang. Functional and molecular evidence for impairment of calcium–activated potassium channels in type-1 diabetic cerebral artery smooth muscle cells.J Cereb Blood Flow Metab,(advance online publication, August 8, 2007; doi:10.1038/sj.jcbfm.9600536) Rakesh Rathore,Yun-min Zheng, Xiao-Qiang Li, Qing-Song Wang, Qing-Hua Liu, Roman R. Ginnan, Harold A. Singer, Ye-Shih Ho and Yong-Xiao Wang. Mitochondrial ROS-PKCepsilon signaling axis is uniquely involved in hypoxic increase in [Ca2+]i in pulmonary artery smooth muscle cells.Biochem Biophys Res Commun, 351(3):784-790.2006. Yun-Min Zheng, Qing-Song Wang, Rakesh Rathore, Wan-Hui Zhang, Joseph E. Mazurkiewicz, Vincenzo Sorrentino, Harold A. Singer, Michael I. Kotlikoff, and Yong-Xiao Wang.Type-3 Ryanodine Receptors Mediate Hypoxia-, but Not Neurotransmitter-induced Calcium Release and Contraction in Pulmonary Artery Smooth Muscle Cells. J. Gen. Physiol. 125: 427-440.2005. Presentations Rakesh Rathore, Yun-Min Zheng, Yong-Xiao Wang.Title: Hypoxia activates NADPH oxidase through mitochondrial ROS–PKCepsilon signaling axis in pulmonary artery smooth muscle cells,51 th Annual Meeting of Biophysical Society, Baltimore, Maryland, March 3-7,2007. Qing-Hua Liu, Rakesh Rathore, Yun-Min Zheng, Yong-Xiao Wang. Title: Role of Intracellular Calcium Release and Sensitivity in Airway Hyperresponsiveness,51 th Annual Meeting of Biophysical Society, Baltimore, Maryland, March 3-7,2007. Ling Dong, Yun-Min Zheng, Rakesh Rathore, Dee Van Riper, Qing-Hua Liu, Yong-Xiao Wang.Title: Functional and molecular evidence for the impaired activity of calcium-activated potassium channels in diabetic cerebral artery smooth muscle cells,51 th Annual Meeting of Biophysical Society, Baltimore, Maryland, March 3-7,2007. Rakesh Rathore, Yun-Min Zheng, Harold A Singer & Yong-Xiao Wang.Title: Acute hypoxia activates PKCepsilon in pulmonary arteries through mitochondria-derived reactive oxygen species,50 th Annual Meeting of Biophysical Society, Salt lake city, Utah, Feb 18-22,2006. Yun-Min Zheng, Rakesh Rathore, Qing song Wang, Harold A. Singer,Vincenzo Sorrentino, Michael I. Kotlikoff and Yong-Xiao Wang. Title: Functional Role of Ryanodine receptors in Pulmonary Artery Smooth Muscle Cells, 48 th Annual Meeting of Biophysical Society, Baltimore, Maryland, Feb 14-18,2004. ### << Previous Next >> [ View All Member Spotlights ] |
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