Role of NALP3 Inflammasome in Tumorigenesis of Mesothelioma
Born and raised in the capital city of Ghana, Accra, my curiosity finally led me to science where I could ask the questions ‘why, where, how and what’ on a daily basis and follow the path to the probable answers. This quest earned me a Bachelor of Science (2003) as well as a Master of Philosophy (2011) degree in Biochemistry from the University of Ghana. During my training for my Master’s degree, I had the wonderful opportunity to do my thesis project here at UVM in the then Shukla/Mossman lab. Cell signaling and cancer biology are part of my central focus in the Shukla lab. I am currently studying the tumorigenesis of malignant mesothelioma and the role inflammation (specifically inflammatory cascades) plays in this fatal cancer. When I am not in the lab, I like to explore Vermont and the surrounding areas with my friends.
Exposure of human peritoneal mesothelial cells to asbestos results in the release of mature IL-1Î² processed by the NALP3 inlfammasome. This is believed to be one of the mechanisms through which asbestos causes chronic inflammation. Chronic inflammation has been shown to be involved in tumorigenesis and fibrosis. Thus the NALP3 inflammasome may play a role in these processes in patients exposed to asbestos. To help understand how asbestos exposure leads to asbestosis and in some cases the rare cancer, mesothelioma, I will be looking at the regulation of asbestos-induced mesothelial to fibroblastic transition (MFT/EMT) by the NALP3 inflammasome as well as regulation of the inflammasome itself using in vitro and in vivo models.
Thompson J and Shukla A. Asbestos risks: past and present (editorial). Air Water Borne Dis 2(1), 2013 (Editorial)
Jill Miller, Joyce Thompson and A. Shukla. Asbestos-Induced Oxidative Stress in Lung Pathogenesis. In, Laher I (ed.), Systems Biology of Free Radicals and Anti-Oxidants, DOI 10.1007/978-3-642-30018-9_201, # Springer-Verlag Berlin Heidelberg 2013. (Book chapter).
Hillegass JM, Miller JM, MacPherson MB, Catherine Westbom, Sayan M, Thompson JK, Macura SL, Perkins TN, Beuschel SL, Alexeeva V, Pass HI, Steele C, Mossman BT, and Shukla A: Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells. Particle and Fiber Toxicology, 10:39, 2013 doi:10.1186/1743-8977-10-39.
Joyce K. Thompson, Catherine Westbom and A Shukla, Malignant mesothelioma: development to therapy. J. Cell. Biochem., 115(1):1-7 2014 (invited review).
Jill M. Miller, Joyce K. Thompson, Maximilian B. MacPherson, Stacie L. Beuschel, Catherine M. Westbom, Mutlay Sayan, and Arti Shukla; Curcumin: A Double Hit on Malignant Mesothelioma (2014) Cancer Prevention Journal (Epub ahead of print).
Sayan M, Shukla A, MacPherson MB, Macura SL, Hillegass JM, Perkins TN, Thompson JK, Beuschel SL, Miller JM, Mossman BT (2014) Extracellular signal-regulated kinase 5 and cyclic AMP response element binding protein are novel pathways inhibited by vandetanib (ZD6474) and doxorubicin in mesotheliomas. Am J Respir Cell Mol Biol 51(5): 595-603.
Thompson JK, Westbom CM, MacPherson MB, Mossman BT, Heintz NH, Spiess P, Shukla A (2014) Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation. Part Fibre Toxicol 11: 24.
Miller JM, Thompson JK, MacPherson MB, Beuschel SL, Westbom CM, Sayan M, Shukla A (2014) Curcumin: a double hit on malignant mesothelioma. Cancer Prev Res (Phila) 7(3): 330-40.
Thompson JK, Westbom CM, Shukla A (2014) Malignant mesothelioma: development to therapy. J Cell Biochem 115(1): 1-7.
Hillegass JM, Miller JM, MacPherson MB, Westbom CM, Sayan M, Thompson JK, Macura SL, Perkins TN, Beuschel SL, Alexeeva V, Pass HI, Steele C, Mossman BT, Shukla A (2013) Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells. Part Fibre Toxicol 10: 39.
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