Department: Pharmacology, Physiology &Toxicology
Research Cluster: Cancer Biology; Neuroscience and Developmental Biology; Toxicology and Environmental Health Sciences
Office: BBSC 435-J | Laboratory: BBSC 416
Phone: (304) 696-3612 | Fax: (304) 696-7391
Studies in my laboratory examine how components of tobacco can promote the progression of lung cancer. Nicotine is the major active and addictive component of cigarette smoke. Our research focuses on how nicotine can facilitate the growth and progression of lung cancers. Although nicotine is not a carcinogen, my studies indicate that it can induce proliferation, angiogenesis and metastasis of lung cancers. Additionally, it can also protect lung cancer cells against chemotherapeutic drug-induced apoptosis. These actions of nicotine are mediated by high affinity nicotinic acetylcholine receptors on lung cancer cells. My lab tries to decipher the signaling pathways by which nicotine promotes the growth and survival of lung tumors. On a more basic level, we try to analyze the physiological function of these neuronal receptors in the lung.
Some of the questions we address are:
- Role of nicotinic receptors in growth of human small cell lung cancer
- Ability of nicotine to increase the expression of nicotinic receptors in lung cancer
- The potential anti-cancer activity of nicotinic receptor antagonists.
We plan to extend these studies to animal models and examine the molecular pathways, which contribute to this process. The transient receptor potential V (TRPV) family of receptors mediates the biological activities of capsaicin. Our future studies will attempt to identify novel ligands for TRPV receptors and test their anti-cancer activity.
Chapters In Scholarly Books
Lau, J. K., Brown, K.C., Dom, A.M. and Dasgupta, P. (2011) Capsaicin: Potential Applications in Cancer Therapy. In: NUTRITION AND CANCER, Ed. P.P Claudio, Bentham Press Inc., London, United Kingdom (in press).
Pillai, S., Dasgupta, P., Chellappan, S.P. (2009) Chromatin immunoprecipitation assays: analyzing transcription factor binding and histone modifications in vivo. In: CHROMATIN PROTOCOLS Ed. SP Chellappan, Methods Mol. Biol., 523, 323-329. Humana Press Inc., NJ, USA.
Dasgupta, P. and Chellappan, S. (2007) Chromatin immunoprecipitation assays: Molecular Analysis of chromatin modification and gene regulation, In: CANCER GENOMICS AND PROTEOMICS Ed. Paul Fischer, Methods Mol. Biol., 383, 135-152. Humana Press Inc., NJ, USA.
Dasgupta, P., Rizwani, W., Pillai, S., Davis, R., Banerjee, S., Hug, K., Lloyd, M., Coppola, D., Haura, E. and Chellappan, S.P. (2011) ARRB1-mediated regulation of E2F target genes in nicotine-induced growth of lung tumors.Journal of National Cancer Institute, 103, 4, 317-33.
Dom, A.M., Buckley, A.W., Brown, K.C., Egleton, R.D., Marcelo, A.J., Proper, N.M., Weller, D.E., Shah, Y.H., Lau, J.K., and Dasgupta, P. (2011) Nicotine promotes retinal angiogenesis via α7-nicotinic receptor and a MMP-2/9 dependent pathway. Investigative Ophthalmology and Visual Science 52, 7, 4428-4438.
Brown, K.C., Witte, T.R., Hardman, W.E., Luo, H., Chen, Y.C., Carpenter, A.B., Lau, J.K. and Dasgupta, P.(2010) Capsaicin displays anti-proliferative activity against human small cell lung cancer in cell culture and nude mice models via the E2F pathway. PLoS ONE, 5, 4, e102343.
Egleton, R. D., Brown, K.C. and Dasgupta, P. (2009) Angiogenic Activity of Nicotinic Acetylcholine Receptors: Implications in Tobacco-related Vascular Diseases. Pharmacology & Therapeutics 121, 2, 205-223.
Dasgupta, P., Rizwani, W., Pillai, S., Kinkade, R., Rastogi, S., Banerjee, S., Kovacs, M., Carless, M., Kim, E., Haura, E., Coppola, D. and Chellappan, S. (2009) Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines. International J. Cancer 124, 1, 36-45.
Egelton, R.D., Brown, K.C., Dasgupta, P. (2008) Nicotinic Acetylcholine Receptors: Multiple Roles in Proliferation and Inhibition of Apoptosis Trends Pharmacol Sci, 29, 151-158.
Kinkade, R., Dasgupta, P., Carie, A., Pernazza, D., Carless, M., Pillai, S., Lawrence, N., Sebti, S.M., Chellappan, S. (2008) A small molecule disruptor of Rb/Raf-1 interaction inhibits cell proliferation, angiogenesis, and growth of human tumor xenografts in nude mice. Cancer Res., 68, 3810-3818.
Dasgupta, P., Rastogi, S., Joshi, B., Pillai, S., Ordonez, D., Morris, M., Haura, E. and Chellappan, S. (2006) Nicotine induces cell proliferation by b-arrestin mediated activation of Src and Rb-Raf-1 pathway. J. Clin. Invest., 116, 2208-17.
Dasgupta, P., Kinkade, R., Joshi, B., DeCook, C., Haura, E. and Chellappan, S. (2006) Nicotine inhibits apoptosis induced by chemotherapeutic drugs by upregulating XIAP and survivin. Proc. Natl. Acad. Sci., USA, 103, 6332-7.
Rastogi, S., Joshi, B., Dasgupta, P*., Morris, M., Wright, K. and Chellappan, S. (2006) Prohibitin facilitates cellular senescence by recruiting specific co-repressors to inhibit E2F-target genes. Mol. Cell. Biol. 26, 4161-71. *equal second author
Dasgupta, P., Padmanabhan, J. and Chellappan, S. (2006) Rb function in the apoptosis and senescence of non-neuronal and neuronal cells: Role in Oncogenesis. Curr. Mol. Medicine 6, 719-29.
Kinkade, R., Dasgupta, P. and Chellappan, S. (2006) The ABCs of Targeting Raf: Novel approaches to Cancer Therapy. Current Cancer Therapy Reviews 2, 305-14.
Dasgupta, P. and Chellappan, S. (2006). Nicotine-mediated cell proliferation and angiogenesis: New Twists to an Old Story. Cell Cycle 5, 2324-28.
Kathleen C. Brown
Brent A. Thornhill
Chirag Patel, Medical Sciences student
Cathryn Stevenson, Medical Sciences student