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The University of Tennessee

The College of Veterinary Medicine

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Howard K. Plummer, III, Ph.D.


Assistant Professor
Department of Pathobiology
College of Veterinary Medicine
The University of Tennessee
2407 River Drive
Knoxville, TN 37996-4542
Phone: (865) 974-8207
FAX: (865) 974-5616
Email

Research Emphasis

Molecular characterization of nicotinic acetylcholine receptors, beta-adrenergic receptors and potassium channels in small cell lung cancer, pulmonary adenocarcinoma, and breast cancer.

Education

  • B.S. Central Michigan University, Mt. Pleasant, MI, 1980.
  • M.A. Western Michigan University, Kalamazoo, MI, 1984.
  • Ph.D. Bowling Green State University, Bowling Green, OH, 1989.

Professional Experience

  • Postdoctoral Fellow,Department of Neurobiology, Anatomy and Cell Science, University of Pittsburgh, Pittsburgh, PA, 1990-1992. Studied role of protein kinase A and its inhibitors on growth and steroid production in Y-1 mouse adrenal cells.
  • Postdoctoral Fellow, Division of Hematology/Oncology, Medical College of Virginia, Richmond, VA, 1992-1995. Characterized expression levels of myc and kit oncogenes in various small cell lung cancer cell lines. Identified and defined the promoter region of the c-kit proto-oncogene in small cell lung cancer and leukemia cell lines.
  • Postdoctoral Fellow,Department of Medicine, Indiana University, Indianapolis, IN, 1995-1996. Investigated silencer element found in some cell lines containing Bcr/Abl oncogene involved in chronic myelogenous leukemia.
  • Postdoctoral Fellow, Department of Pathology, University of Tennessee, Knoxville, TN, 1997-2001. Molecular characterization of nicotinic acetylcholine receptors in small cell lung cancer cells and ß-adrenergicreceptors in adenocarcinoma cell lines using RT-PCR.
  • Assistant Professor,Department of Pathology, University of Tennessee, Knoxville, TN, 2001-present.

Teaching

  • Train and teach technicians and graduate students in molecular laboratory techniques and cell culture.
  • CEM 609: Mechanisms of Disease
  • Ph.D. graduate student in lab: Michael Hance, August 2005-present

Research Interests

Breast cancer is the leading cancer in women and smoking and regular alcohol consumption are risk factors. Studies in human cancer cell lines or in animal models have shown that the growth of a type of cancer called adenocarcinoma in the lungs, pancreas and colon are under control of a cell surface receptor in the beta-adrenergic system. The beta-adrenergic system is part of the sympathetic nervous system, and beta-blockers are used in humans for the treatment of hypertension and angina. Data from our laboratory has indicated that similar to these cancers in other organs, growth of a subset of human breast cancers is under control of this same beta-adrenergic cell surface receptor-cellular signaling system. A recent report in the literature indicated high levels of a potassium channel (GIRK1) in primary breast carcinomas. We have identified a functional link between the beta-adrenergic receptor pathway and the GIRK1 potassium channel in human breast cancer cell lines. Data from our laboratory has indicated a carcinogen found in tobacco smoke 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) stimulates this system in breast cancer cells. Reports from the literatur ehave indicated that ethanol stimulates the GIRK channels in other cell types. The research in my laboratory explores the molecular role of this channel and its interaction with beta-adrenergic signaling pathways, including effects of ethanol and tobacco carcinogens on these pathways. A second research project in my laboratory expands the GIRK/beta-adrenergic studies into small cell lung cancer (SCLC). We have determined that GIRK mRNA and protein are expressed small celllung cancer SCLC cell lines, and treatment of SCLC cell line NCI-H69 with beta-adrenergic antagonist ICI1l8,55l led to slight decreases of GIRKI mRNA expression levels. Treatment of NCI-H69 with β-adrenergic agonist isoproterenol decreased growth rates in these cells. We feel that this data may indicate that stimulation of GIRK channels and/or stimulation of beta-adrenergic signaling may activate similar signaling pathwaysin both SCLC and breast cancer, but lead to different results. This research was recently published by BMC Cancer. The tobacco carcinogen NNK also has been found to stimulate nicotinic acetylcholine receptors in SCLC. Another research project in my laboratory will be to define how nicotine and NNK effect expression of nicotinic receptors in lung cancer. We have determined that the α7 nicotinic receptor is ubiquitously expressed in human lung cells, and the over expression of this receptor may be involved in the effects of tobacco carcinogens in the lungs. A paper based on our work withthe α7 nicotinic receptor was recently published in Respiratory Research. In addition, preliminary data indicates that treatment of small cell lung cancer cell lines with beta-adrenergic agonists grown at high CO 2 levels (%) inhibits proliferation of small cell lung cancer cell lines. This data could indicate alink between use of beta-adrenergic agonists and antagonists and chronic obstructive pulmonary disease due to the fact that this disease is characterized by high levels of CO2 in localized areas of the lung. External grant funding: "GIRK channels, beta-adrenergic signaling and breast cancer" Philip Morris External Research Program, July I, 2004 - June 30, 2007

Professional Societies

  • American Association for Cancer Research
  • American Society for Cell Biology.

Publications

  • Plummer III, H.K., Dhar, M., Cekanova, M. and Schuller, H.M. 2005. Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung cancer celllines. BMC Cancer 5: 104. (10 pages).
  • Plummer III, H.K., Dhar, M. and Schuller, H.M. 2005. Expression of the α7 nicotinic acetylcholine receptor in human lungcells. Respiratory Research 6: 29. (9 pages).
  • Plummer III, H.K., Yu, Q., Cakir, Y. and Schuller, H.M. 2004. Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines. BMC Cancer 4: 93.(11 pages).
  • Song, P., Wei, J., PlummerIII, H. and Wang, H-C. R. 2004. Potentiated capase-3 i nRas-transformed 10T1/2 cells. Biochemical and Biophysical Research Communications 322: 557-564.
  • Heckman, CA., Urban, J.M., Cayer, M.,Li, Y., Boudreau, N., Barnes, J., Plummer III, H.K., Hall,C., Kozma, R. and Lim, L. 2004. Novel p2l-activated kinase-dependent protrusions characteristically formed at the edge of transformed cells. Experimental Cell Research 295:432-447.
  • Mei, J., Hu, H., McEntee, M.,Plummer III, H., Song, P., and Wang, H-C.R. 2003. Transformation of noncancerous human breast epithelial cell line MCF10A by the tobacco-specific carcinogen NNK. Breast Cancer Research and Treatment 79:95-105.
  • Schuller, H.M., Plummer III,H.K., and Jull, B.A. 2003. Receptor mediated effects of nicotine and its nitrosated derivative NNK on pulmonary neuroendocrine cells. Anatomical Record 270: 51-58.
  • Cakir, Y., Plummer III, H.K.,Tithof, P.K., and Schuller, H.M. 2002. Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines. International Journal of Oncology 21:153-157.
  • Jull, B.A., Plummer III, H.K.,and Schuller, H.M. 2001. Nicotinic receptor-mediated activation by the tobacco-specific nitrosamine NNK of a Raf-1/MAP kinase pathway, resulting in phosphorylation of c-myc in human small cell lung carcinoma cells and pulmonary neuroendocrine cells. Journal Cancer Research and Clinical Oncology 127:707-717.
  • Schuller, H.M., Plummer III,H.K., Bochsler, P.N., Dudrick, P., and Harris, R.E. 2001. Co-expression of b-adrenergic receptors and cyclooxygenase 2 in pulmonary adenocarcinoma. International Journal of Oncology 19: 445-449.
  • Heckman, C.A., Plummer III,H.K., and Mukherjee, R. 2000. Enhancement of the transformed shape phenotype by microtubule inhibitors and reversal by an inhibitor combination. International Journal of Oncology16:709-723.
  • Schuller, H.M., Jull, B.A., Sheppard, B.J., and Plummer, H.K. 2000. Interaction of tobacco-specific toxicants with the neuronal a7 nicotinic acetylcoline receptor and itsassociated mitogenic signal transduction pathway: potential role in lung carcinogenesis and pediatric lung disorders. European Journal of Pharmacology 393: 265-277.
  • Plummer III, H.K., Sheppard, B.J. and Schuller, H.M. 2000. Interaction of tobacco-specific toxicants with nicotinic cholinergic regulation of fetal pulmonary neuroendocrine cells: Implications for pediatric lung disease. Experimental Lung Research 26: 121-135.
  • Sheppard, B.J., Williams, M., Plummer, H.K. and Schuller, H.M. 2000. Activation of voltage-operated Ca2+-channels in human small cell lung carcinoma by the tobacco-specific nitrosamine4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. International Journal of Oncology 16: 513-518.
  • Schuller, H.M., Tithof, P.K., Williams, M. and Plummer III, H. 1999. The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone is aß-adrenergic agonist and stimulates DNA synthesis in lung adenocarcinoma via ß-adrenergic receptor-mediated release of arachidonic acid. Cancer Research 59: 4510-4515.
  • Park, G.H., Plummer III, H.K.and Krystal, G.W. 1998. ive Sp1 binding is critical for maximal activity of the human C-Kit promoter. Blood 11:4138-4149.
  • Heckman, C.A., Plummer III,H.K. and Runyeon, C.S. 1996. Persistent effects of phorbol12-myristate 13-acetate: possible implication of vesicle traffic. Journal of Cellular Physiology 166: 217-230.
  • Plummer III, H., Catlett, J.,Leftwich, J., Armstrong, B., Carlson, P., Huff, T. and Krystal, G.1993. c-myc expression correlates with suppression of C-Kitproto-oncogene expression in small cell lung cancer cell lines. Cancer Research 53: 4337-4342.
  • Murray, S.A., Plummer III,H.K., Leonard II, E.E. and Deshmukh, P. 1993. Regulation of the 12-o -tetradecanoyl-phorbol-13-acetate-induced inhibition of intercellular communication. Anatatomical Record 235:1-11.
  • Plummer III, H.K., Dillard, C.Y. and Murray, S.A. 1992. Hoechst 33342 for microfluorimetric measurement of adrenocortical tumor cell proliferation. InVitro Cellular & Developmental Biology 28A: 4-6.
  • McCauley, J., Farkus, Z., Prasad,S.J., Plummer III, H. and Murray, S.A. 1991. Cyclosporine A and FK 506 induced inhibition of renal epithelial cell proliferation. Transplant Proceedings 23: 2829-2830.
  • Plummer III, H.K. and Heckman,C.A. 1990. Transient expression of the transformed phenotype stimulated by 12-o -tetradecanoyl phorbol-13 acetate.Experimental Cell Research 188: 66-74.

Post-doc Fellows

  • Dr. Qiang Yu, January - November 2003