Shampa Chatterjee

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Research Associate Professor of Physiology
Department: Physiology

Contact information
Institute for Environmental Medicine,
1 John Morgan
Philadelphia, PA 19104
Office: 215 898 9101 (Off)
Fax: 215 898 0868
PhD (Chemistry)
Indian Institute of Technology, Bombay, India, 1997.
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Description of Research Expertise

Cells are continuously exposed to mechanical forces from our environment. Irrespective of whether these are externally applied or arising from physiological “events”, mechanical forces trigger changes in intracellular biochemical signaling and gene expression, eventually leading to cell differentiation, migration and apoptosis.

A major focus of my research is toward understanding the cellular, specifically endothelial, response to mechanical stimulation. We study endothelial responses in the context of stop of flow, as would occur with obstructive pathologies such as blood clots, surgical procedures etc. As interrupted blood flow also results in compromised oxygen supply, we have chosen an isolated lung model where oxygen delivery is maintained during the period that flow is stopped; this enables us to study the mechanical aspects of flow alone. Using isolated lungs and cells in vitro, we have reported that stop of blood flow triggers a signaling cascade that causes reactive oxygen species (ROS) production; subsequent downstream signals drive cell proliferation and revascularization. We believe that revascularization is an attempt to restore the impeded flow.

The sensing of stop of flow or mechanotransduction occurs via mechanosensors. Work from our lab showed that several elements on the endothelial cell surface participate in mechanotransduction with stop of flow. We thus posit a “mechanosome” hypothesis for endothelial mechanotransduction. Mechanosomes comprising of caveolae, platelet endothelial cell adhesion molecule (PECAM-1), vascular endothelial growth factor receptor (VEGFR2), vascular endothelial cadherin (VE-cadherin) and possibly other elements are quiescent under flow (OFF mechanosome) but with stop of flow the mechanosome network interacts with other signaling cascades (ON mechanosome). The physiological response to stop of flow is cell proliferation and angiogenesis. We observe that the stop of flow signal is transduced via ROS and transcription factors (HIF-1α, NFB, AP-1) into a revascularization response. Currently we are engaged in understanding various aspects of sensing and physiological responses.

Another of our research interests lies in understanding the role of endothelium in driving pathologies such as lung inflammation. The onset of lung inflammation is characterized by activation and recruitment of neutrophils from systemic circulation into the lung. Crucial to this entire process is the initial association of neutrophils with endothelial cells, which reportedly occurs via low affinity adhesion molecules such as vascular cell adhesion molecule-1 (VCAM)and intercellular adhesion molecule-1 (ICAM-1). To visualize CAMs in inflamed lungs, we employ quantum dot (QD) technology, which coupled with fluorescence imaging techniques is a powerful tool that allows for detection of various proteins in situ and in vivo. QDs are conjugated to anti-VCAM and these probes are then used to “watch” for adhesion molecule expression in endothelium in vivo. In addition to monitoring our target molecules, this technology allows us to studying signaling events in situ and in vivo.

Description of Itmat Expertise

Inflammation, endothelial cells, lung signaling

Selected Publications

Elizabeth Browning, Hui Wang, Nankang Hong, Kevin Yu, Donald G. Buerk, Kristine DeBolt, Daniel Gonder, Elena M. Sorokina, Puja Patel, Diva D. De Leon, Sheldon I. Feinstein, Aron B. Fisher and Shampa Chatterjee : Mechanotransduction drives post ischemic revascularization through KATP channel closure and production of reactive oxygen species. Antioxidants and Redox Signaling 20(6): 872-886, February 2014.

Rebecca L. Orndorff, Nankang Hong, Kevin Yu, Sheldon I. Feinstein, Blaine J. Zern, Aron B. Fisher, Vladimir R. Muzykantov, Shampa Chatterjee: NOX2 in lung inflammation: Quantum dot based in situ imaging of NOX2 mediated expression of vascular cell adhesion molecule-1 (VCAM) American Journal of Physiol. Lung Cell and Mol Physiol. 306: L260-268, January 2014.

John Noel, Hui Wang, Nankang Hong, Jian-Qin Tao, Kevin Yu, Elena M. Sorokina, Kristine DeBolt, Michelle Heayn, Victor Rizzo, Horace Delisser, Aron B. Fisher and Shampa Chatterjee: PECAM-1 and caveolae form the mechanosensing complex necessary for NOX2 activation and angiogenic signaling with stopped flow in pulmonary endothelium Am J Physiology : Lung Cell Mol Physiol 305: L805-818, October 2013.

Noel, J and S. Chatterjee : Shear Stress and Vascular Inflammation; A study in the Lung. In Inflammation, Molecular Pathophysiology, Nutritional and Therapeutic Interventions. Eds, Roy, S, Sen C. K. and Roychowdhury, S. (eds.). Taylor and Francis, Florence, KY, Page: 229, 2012.

Lee I, Dodia C, Chatterjee S, Feinstein SI, Fisher AB. : Protection against LPS-induced acute lung injury by a mechanism based inhibitor of NADPH-oxidase (Type 2). Am J Physiol Lung Cell Mol Physiol. 306(7): L635-644, April 2014.

Shampa Chatterjee and Aron Fisher: Mechanotransduction: Forces, Sensors and Redox Signaling. Antioxidants and Redox Signaling 20(6): 868-871, February 2014.

Shampa Chatterjee and Aron Fisher: Mechanotransduction in the Endothelium: Role of membrane proteins and reactive oxygen species in sensing, transduction and transmission of the signal with altered blood flow Antioxidants and Redox Signaling 20(6): 899-913, February 2014.

Lee I, Dodia C, Chatterjee S, Zagorski J, Mesaros C, Blair IA, Feinstein SI, Jain M, Fisher AB.: A novel nontoxic inhibitor of the activation of NADPH oxidase reduces reactive oxygen species production in mouse lung. J Pharmacol Exp Ther. 345(2): 284-296, March 2013.

Chatterjee, S, Browning, E.A., Hong, N., DeBolt, K., Sorokina, E., Liu, W. and Aron B. Fisher: Membrane depolarization is the trigger for PI3Kinase/Akt activation and leads to the generation of reactive oxygen species. American Journal of Physiology: Heart and Circ Physiology 302(1): H105-14, January 2012.

Chatterjee S, Feinstein SI, Dodia C, Sorokina E, Lien YC, Nguyen S, Debolt K, Speicher D, Fisher AB. : Peroxiredoxin 6 phosphorylation and subsequent phospholipase A2 activity are required for agonist-mediated activation of NADPH oxidase in mouse pulmonary microvascular endothelium and alveolar macrophages. J Biol Chem. Am Society for Biochemistry and Molecular Biology, 286: 11696-706, 2011.

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Last updated: 05/19/2015
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