Department: Pharmacology, Physiology &Toxicology
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.
- Selected to be a co-chair of the “Tumor Microenvironment and Metastasis” Special Interest Group in the American Society of Investigative Pathology. (http://www.asip.org/SIGs/TMM/), 2015
- Dean Award for Excellence in Basic Science Research, Marshall University School of medicine, 2013
- John and Francis Rucker Outstanding Graduate Faculty Award, Marshall University, 2011
- ASPET-Astellas Award in translational Pharmacology, 2009
- Marshall University Distinguished Artists and Scientists Award (MU-DASA), 2009
Chapters In Scholarly Books
Pillai, S., Dasgupta, P. and Chellappan S.P. (2015) Chromatin immunoprecipitation assays: analyzing transcription factor binding and histone modifications in vivo. Methods Mol. Biol. 1288, 4129-4146.
Lau, J. K., Brown, K.C., Dom, A.M. and Dasgupta, P. (2012) Capsaicin: Potential Applications in Cancer Therapy. In: NUTRITION AND CANCER, Ed. P.P. Claudio and R.M. Niles, 15-25, Bentham Press Inc., London, United Kingdom.
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.
Chen, J., Chen, A.Y., Huang, H., Ye, X., Rollyson, W.D., Perry, H.E., Brown, K.C., Rojanasakul, Y., Rankin, G.O., Dasgupta, P., Chen, Y.C. (2015) The flavonoid nobiletin inhibits tumor growth and angiogenesis of ovarian cancers via the Akt pathway. Int. J. Oncology 46, 6, 2629-2638.
Rollyson, W.D., Stover, C.A., Brown, K.C, Perry, H.E., Stevenson, C.D., McNees, C.A., Ball, J.G., Valentovic, M.A. and Dasgupta, P. (2014) Bioavailability of capsaicin and its implications for drug delivery. Controlled Release 196, 8, 96-105.
Lau, J.K., Brown, K.C., Dom, A.M., Witte, T.R., Thornhill, B.A., Crabtree, C.M., Perry, H.E., Brown, J.M., Ball, J.G., Creel, R.G., Damron, C.L., Rollyson, W.D., Stevenson, C.D., Hardman, W.E., Valentovic, M.A., Carpenter, A.B. and Dasgupta, P. (2014) Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway. Apoptosis.19:1190-201
Brown, K.C., Perry, H. E., Lau, J.K., Jones, D.V., Pulliam, J.F., Thornhill, B.A., Crabtree, C.M., Luo, H., Chen, Y.C. and Dasgupta, P. (2013). Nicotine induces the upregulation of the alpha7-nicotinic receptor (α7-nAChR) in human squamous cell lung cancer cells via the Sp1/GATA pathway. J. Biol. Chem. 288, :33049-59
Lau, J.K., Brown, K.C., Thornhill, B.A., Crabtree, C.M., Dom, A.M., Witte, T.R., Hardman, W.E., McNees, C.A., Stover, C.A., Luo, H., Chen, Y.C., Carpenter, A.B., Dasgupta, P. (2013) Inhibition of cholinergic signaling causes apoptosis in human bronchioalveolar carcinoma. Cancer Research, 74, 1328-1339.
Santanam, N., Thornhill, B.A., Lau, J.K., Crabtree, C.M., Cook, C.R., Brown, K.C., Dasgupta P. (2012) Nicotinic acetylcholine receptor signaling in atherogenesis. Atherosclerosis, 225, 264-273.
Brown, K.C., Lau, J.K., Luo, H., Crabtree, C.M., Shah, Y.H., Shiflett, B.S., Marcelo, A.J., Proper, N.A., Hardman, W.E., Egleton, R.D., Chen, Y.C., Mangiarua, E.I., Dasgupta P. (2012) MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway. Angiogenesis, 15, 99-114.
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.
Kathleen C. Brown – Research Technician
Haley E. Perry – Research Technician
Austin Akers – Undergraduate student
Mathew Noel Eskew – Undergraduate student
John Hurley – M.S. Medical Sciences student