Role of NALP3 Inflammasome in Tumorigenesis of Mesothelioma
In the Shukla lab, we study signaling pathways involved in malignant mesothelioma tumorigenesis/progression and how these can be exploited for the development of new chemotherapeutics and co-therapies. My work focuses on the regulation of the inflammasome in response to asbestos and the role such regulation plays in MM tumorigenesis and progression. I like to explore the natural beauty in the Lake Champlain area and the rest of Vermont in my free time.
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).
Thompson JK, Westbom CM, MacPherson MB, Mossman BT, Heintz NH, Spiess P, Shukla A Asbestos modulates thioredoxin-thioredoxin interacting protein interaction to regulate inflammasome activation Part Fibre Toxicol. 2014 May 20;11:24.
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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