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Dennis K. Watson, Ph.D.

Dennis K. Watson, Ph.D.

Professor, Department of Pathology & Laboratory Medicine
Professor, Department of Biochemistry and Molecular Biology
Associate Director for Education and Training, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC

Business Address:
Department of Pathology and Laboratory Medicine
The James E. Clyburn Research Center
Medical University of South Carolina
68 President Street
Charleston, SC 29425

Office: BEB BE406
Laboratory: BEB BE432

Office Phone: (843) 876-2376
Laboratory Phone: (843) 876-2379
Fax: (843) 876-2375

Visit Dr. Watson's Laboratory

EDUCATION:

BS 1972 University of Southern California
Ph.D. 1980 Johns Hopkins University

RESEARCH INTERESTS:

Malignancies can result from mutations in oncogenes or tumor suppressor genes, including genes that encode for transcription factors. Such aberrations result in the disruption of signal-transduction pathways that insure proper functioning of cellular processes. Disruption in the normal functions of trans-acting factors can lead to cancer as well as abnormal development. My research is focused in two areas: (1) Molecular biology of gene regulation. To define the functional role of the ETS gene family of transcription factors during cellular proliferation and differentiation and transformation. (2) Molecular genetics of cancer. To identify and functionally characterize genes critical for carcinogenic transformation, metastasis, and progression.

SELECTED PUBLICATIONS:

  1. Spyropoulos, D.D., Pharr, P., Lavenburg, K.R., Jackers, P., Papas, T.S., Ogawa, M. and Watson, D.K.: Hemorrhage, impaired hematocytopenia and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor. Mol and Cell Biol. 20:5643-52, 2000.
  2. Kawada, H., Ito, T., Pharr, P.N., Spyropoulos, D.D., Watson, D.K. and Ogawa, M.: Defective megakaryopoiesis and abnormal erythroid development in Fli-1 gene targeted mice. Int. J. Hematol. 73:463-8, 2001.
  3. Feldman, R.J., Sementchenko, V.I., Gayed, M., Fraig, M.M. and Watson, D.K.: Pdef expression in human breast cancer is correlated with invasive potential and altered gene expression, Cancer Research: 63: 4626-4631, 2003.
  4. Yordy, J. S., Li, R., Sementchenko, V. I., Pei, H., Muise-Helmericks. R. C. and Watson, D. K.: SP100 Expression Modulates ETS1 Transcriptional Activity and Inhibits Cell Invasion, Oncogene 23: 6654-6665, 2004.
  5. Jackers, P., Szalai, G., Moussa, O., and Watson, D.K. Ets-dependent regulation of target gene expression during megakaryopoiesis, J. Biol. Chem, 279: 52183-52190, 2004.
  6. Masuya, M., Moussa, O., Abe, T., Deguchi, T., Higuchi, T., Spyropoulos, D. D., Watson, D. K., Ogawa, M.: Dysregulation of granulocyte, monocyte, erythrocyte and NK cell in Fli-1 gene targeted mice, Blood, 105: 95-102, 2005.
  7. Yordy, J.S., Moussa, O., Pei, H., Chaussabel, D., Li, R., and Watson, D.K., SP100 inhibits ETS1 activity in primary Endothelial cells, Oncogene 24: 916-931, 2005.
  8. Fraser, M.M., Watson, P.M., Fraig, M., Kelley, J.R., Nelsen, P., Boylan, A., Cole, D.J. and Watson, D.K.: CaSm mediated transformation is associated with alterations in mRNA stability and gene expression. Cancer Research 65: 6228-6236, 2005.
  9. Pei, H., Li, C., Adereth, Y., Hsu, T., Watson, D. K. and Li, R. Caspase-1 is a direct target gene of ETS1 and plays a role in ETS1-induced apoptosis, Cancer Research, 65: 7205-7213, 2005.
  10. Seth, A. and Watson, D.K.: Ets Transcription Factors and their Emerging Roles in Human Cancer, European J. Cancer, 41:2462-2478, 2005.
  11. Moussa O. M., Yordy, J. S., Abou-Elenin H., Sinha, D., Bissada, N. K., Halushka, P.V., Ghoneim, M. A. and Watson, D. K.: Prognostic and Functional Significance of Thromboxane A2 Synthase Gene Overexpression In Invasive Bladder Cancer, Cancer Research 65: 11581-11587, 2005.
  12. Yan, Y., Rubinchik, S., Wood, A.L., Gillanders, W.E., dong, J-Y., Watson, D.K., and Cole, D.J.: Bystander effect contributes to the antitumor efficacy of CaSm antisense gene therapy in a preclinical model of advanced pancreatic cancer, Molecular Therapy 13, 357-365, 2006.
  13. Moussa, O. M., Abou-Enein, H., Bissada, N. K., Keane, T., Ghoneim, M. A., Watson, D.K.: Evaluation of survivin reverse transcriptase polymerase chain reaction (rt-pcr) for non-invasive detection of bladder cancer, J. Urology 175: 2312-2316, 2006.
  14. Forough, R., Weylie, B., Collins, C., Parker, J.L., Zhu, J., Barhoumi, R. and Watson, D.K.: Transcription factor Ets-1 regulates fibroblast growth factor-1 (FGF-1) mediated angiogenesis in vivo: Role of Ets-1 in regulation of PI3K/AKT/MMP-1 pathway, Journal of Vascular Research, 43:327–337, 2006.
  15. Pang, L., Xue, H.-H., Szalai, G., Wang, X., Wang, Y., Watson, D.K., Leonard, W.J., Blobel, G., and Poncz, M.: Maturation stage-specific regulation of megakaryocytic genes by pointed-Domain Ets proteins, Blood, 108:2198-2206, 2006. (Epub)
  16. Szalai, G., LaRue, A. C., and Watson, D.K.: Molecular mechanisms of megakaryopoiesis, Cellular and Molecular Life Sciences (CMLS), 63:2460-2476, 2006. (Epub)
  17. Turner, D., Moussa, O., Sauane, M., Fisher, P.B., and Watson, D.K.: PDEF is a mediator of metastatic potential through the inhibition of migration and invasion in breast cancer, Cancer Research 67: 1618-25, 2007. (Epub)
  18. Watson, D. K., Abate-Shen, C., and Gelmann, E.: Molecular Pathogenesis of Prostate Cancer, American Society of Clinical Oncology 2007 Education Book, 43rd ASCO Annual Meeting, 267-271, 2007.
  19. Higuchi. T., Bartel, F., Masuya, M., Deguchi, T., Henderson, K., Li, R., Muise-Helmericks, R., Ogawa, M., Kern, M., Watson, D.K., and Spyropoulos, D. D.: Thymomegaly, Microsplenia and defective homeostatic proliferation of peripheral lymphocytes p51-Ets1 Isoform-Specific Null Mice, Molecular and Cellular Biology 27: 3353–3366, 2007. (Epub)
  20. Markiewicz, M., Asano, Y., Znoyko, S., Gong, Y., Watson, D. K., and Trojanowska, M.: Distinct effects of gonadectomy in male and female mice on collagen fibrillogenesis in mouse skin, Journal of Dermatological Science, 47:217-226, 2007. (Epub)
  21. Turner, D. P., Findlay, V. J., Moussa, O., and Watson, D. K.: Defining ETS Transcription Regulatory Networks and their Contribution to Breast Cancer Progression Journal of Cellular Biochemistry, 102: 549-559, 2007. (Epub)
  22. Moussa, O., Riker, M., Klein, J., Fraig, M., Halushka, P. V. and Watson, D. K.: Inhibition of Thromboxane Synthase Activity Modulates Bladder Cancer Cell Responses to Chemotherapeutic Agents, Oncogene, 27: 55-62, 2008 (Epub)
  23. Turner, D.P. and Watson, D.K.: ETS Transcription Factors - Oncogenes and Tumor Suppressor Genes that Drive Prostate Cancer, Expert Review of Anticancer Therapy, 8: 33-42, 2008. (Epub)
  24. Watson, P. M., Miller, S. W., Fraig, M.M., Cole, D.J., Watson, D.K., and Boylan, A.M. CaSm (LSm-1) over-expression found in lung cancer and mesothelioma is required for transformed phenotypes, American Journal of Respiratory Cell and Molecular Biology, 38:671-678, 2008
  25. Moussa, O., Ashton, A., Fraig, M., Garrett-Mayer, E., Ghoneim, M. A., Halushka, P. V., and Watson, D. K.: Thromboxane (TP) beta receptors in human bladder cancer: Role in pathogenesis and prognosis in bladder cancer, Cancer Research, 68: 4097-104, 2008
  26. Zhang, X.K., Moussa, O., LaRue, A., Bradshaw, S., Molano, I., Spyropoulos, D.D., Gilkeson, G., Watson, D.K.: The Fli-1 Transcription Factor Modulates Marginal Zone B Cell and Follicular B Cell Development in Mice, J. Immunology 181: 1644–1654, 2008.
  27. Turner, D.P, Findlay, V.J., Kirven, A.D., Moussa, O, and Watson, D.K.: Global gene expression analysis identifies PDEF transcriptional networks regulating cancer cell migration during metastatic progression, Molecular Biology of the Cell 19: 3745-3757, 2008.
  28. Findlay, V. J., Moussa, O., Turner, D. P., and Watson, D. K.: MicroRNA-mediated inhibition of PDEF mRNA translation affects PDEF regulatory networks in human breast cancer, Cancer Research, 68:8499–506, 2008. PMID: 18922924; PMC: 2680499; NIHMSID # 65608; PMCID: PMC2680499.
  29. Asano, Y., Markiewicz M, Kubo M, Znoyko S, Szalai G, Watson D.K., and Trojanowska M.: C-terminal Domain of transcription factor Fli1 mediates repression of fibrillar collagen genes in mouse skin, Molecular and Cellular Biology, 29: 425–434, 2009. PMID: 19001092; PMC: 2612518
  30. Elkareh, J., Periyasamy, S., Shidyak, A., Vetteth, S., Schroeder, J., Raju, V., Hariri, I., El-Okdi, N., Gupta, S., Fedorova, L., Liu, J., Fedorova, O., Kahaleh, M., Xie, Z., Malhotra, D., Watson, D. K., Bagrov, A., and Shapiro, J.: Marinobufagenin Induces Increases in Procollagen Expression in a Process Involving Protein Kinase C and Fli-1: Implications for Uremic Cardiomyopathy, Am J Physiol Renal Physiol 296: F1219–F1226, 2009. PMID: 19261738; PMC: 2681369
  31. Kruse, E. A., Loughran, S. J., Baldwin, T. M., Josefsson, E. C., Ellis, S., Watson, D. K., Nurden, P., Metcalf, D., Hilton, D. J., Alexander, W. S., and Kile, B. T.: Dual Requirement for Fli-1 and Erg in Hematopoietic Stem Cells and the Megakaryocyte Lineage, PNAS 106: 13814-13819. PMID: 19666492; PMC: 2728977
  32. Sera, Y., LaRue, A. C., Moussa, O., Mehrotra, M., Duncan, J. D., Williams, C. R., Nishimoto, E., Schulte, B. A., Watson, P. M., Watson, D. K., and Ogawa, M.: Hematopoietic Stem Cell Origin of Adipocytes, Experimental Hematology 37:1108–1120; PMID: 19576951; NIHMS141763
  33. Moussa, O., Turner, D., Feldman, R. J., Sementchenko, V. I., McCarragher, B., Desouki, M. M., Fraig, M., and Watson, D.K.: PDEF is a negative regulator of colon cancer cellular growth and migration, J Cellular Biochemistry, 108:1389–1398, 2009; PMID: 19830706
  34. Shirai, K., Sera, Y., Bulkeley, W., Mehrotra, M., Moussa, O., LaRue, A.C., Watson, D. K., Stuart, R. K., Lazarchick, J. and Ogawa, M.: Hematopoietic Stem Cell Origin of Human Fibroblasts: Cell Culture Studies of Female Recipients of Gender Mismatch Stem Cell Transplantation and a Patient with Chronic Myelogenous Leukemia, Experimental Hematology 37:1464–1471, 2009. PMID: 19786066
  35. Asano, Y., Stawski, L., Hant, F., Highland, K., Silver, R., Szalai, G., Watson, D. K., Trojanowska, M.: Endothelial Fli1 deficiency impairs vascular homeostasis – a role in scleroderma vasculopathy, Amer J Pathology 176: 1983-1998, 2010. PMID: 20228226; PMC 2843486
  36. Watson, D. K., Turner, D. P., Scheiber, M. N., Findlay, V. J., and Watson, P. M.: ETS transcription factor expression and conversion during prostate and breast cancer progression, Open Cancer Journal 3: 24-39, 2010.
  37. Watson, P. M. and Watson, D. K.: Alternative splicing in prostate and breast cancer, Open Cancer Journal, 3: 62-73, 2010.
  38. Ogawa, M., LaRue, A. C., Watson, P. M. and Watson, D. K.: Hematopoietic Stem Cell (HSC) Origin of Mesenchymal Cells, International Journal of Hematology, 91:353–359, 2010 PMID: 20336396
  39. Ogawa, M., LaRue, A. C., Watson, P. M. and Watson, D. K.: Hematopoietic Stem Cell Origin of Connective Tissues, Experimental Hematology 38:540–547, 2010. PMID: 20412832
  40. Moussa, O., LaRue, A. C., Abangan, Jr., R. S., Williams, C. R., Zhang, X. K., Masuya, M., Gong, Y. Z., Spyropoulos, D. D., Ogawa, M., Gilkeson, G., and Watson, D. K.: Thrombocytopenia in mice lacking the carboxy-terminal regulatory Domain of the Ets transcription factor Fli1, Molecular and Cellular Biology 30: 5194-5206, 2010.
  41. Mathenia, J., Reyes-Cortes, E., Molano, I., Ruiz, P., Watson, D. K., Gilkeson, G. S., Zhang, X. K.: Impact of Fli-1 transcription factor on lupus disease development in NZM2410 mice, Clinical and Experimental Immunology 162: 362–371, 2010.
  42. Findlay, V. J., Turner, D. P., Yordy, J. S., McCarragher, B., Shriver, M. R., Szalai, G., Watson, P. M., LaRue, A. C., Moussa, O, and Watson, D. K.: The negative regulation of Slug by PDEF inhibits breast cancer cell migration and invasion, Genes & Cancer 2: 120-129, 2011. NIHMS # 293542. PMCID: PMC3111250
  43. Camp, E.R., Findlay, V.J., Vaena, S.G., Walsh, J., Lewin, D.N., Turner, D.P., Cole, D.J., Watson, D.K.: Slug expression enhances tumor formation in a non-invasive rectal cancer pre-clinical model, Journal of Surgical Research 170: 56-63, 2011. PMID: 21470622
  44. Turner, D. P., Findlay, V, J., Moussa, O., Sementchenko, V. I., Watson, P. M., LaRue, A. C., Desouki, M. M., Fraig, M., Watson, D. K.: Mechanisms and functional consequences of PDEF protein expression loss during prostate cancer progression, The Prostate, 71:1723-1735, 2011. PMID: 21446014 NIHMS # 277888.
  45. Kornblau, S. M., Qiu, Y. H., Zhang, N., Coombes, K. C., and Watson, D. K.: Abnormal Expression of Friend Leukemia Virus Integration 1 Protein Is an Adverse Prognostic Factor in Acute Myeloid Leukemia, Blood 11 58: 604-5612, 2011.
  46. Moussa, O., Ciupek, A., Watson, D. K., and Halushka, P. V.: Urinary Thromboxane B2 and Thromboxane Receptors in Bladder Cancer: Opportunity for detection and monitoring, Prostaglandins & Other Lipid Mediators 96: 41-44, 2011.
  47. Little, E., Wang, C., Watson, P. M., Watson, D. K., Cole, D. J., Camp, E. R.: Novel Immunocompetent Murine Models Representing Advanced Local and Metastatic Pancreatic Cancer, Journal of Surgical Research, in press.
  48. Rossa, C. Jr., Sommer, G., Spolidorio, L. C., Rosenzweig, S. A., Watson, D. K., and Kirkwood, K. L.: Loss of SOCS3 is an early event in HNSCC. Altered subcellular localization as a possible mechanism involved in proliferation, migration and invasion. PLoS one 7: e45197, 2012.
  49. Suzuki, E., Karam, E., Williams, S., Watson, D. K., Gilkeson, G., Zhang, X. K.: Fli-1 transcription Factor Affects Glomerulonephritis Development by Regulating Expression of MCP-1 in Endothelial Cells in the Kidney, Clinical Immunology, 145, 201–208, 2012. PMID: 23108091; PMCID: PMC3501541
  50. Qin, Z., Dai, L., Defee M., Findlay, V. J., Watson, D. K., Toole, B. P., Cameron, J., Peruzzi, F., Kirkwood, K.L., Parsons, C. KSHV suppression of DUSP1 facilitates cellular pathogenesis following de novo infection, Journal of Virology 87: 621–635, 2012. PMID: 23097457

PAPERS IN PRESS:

  1. Suzuki, E., Williams, S. Gilkeson, G., Watson, D. K. and Zhang, X. K: The Transcription Factor Fli-1 Regulates Monocytes, Macrophages, and Dendritic Cell Development in Mice, Immunology, in press.
  2. Findlay, V. J., LaRue, A. C., Turner, D. P., Watson, P. M. and Watson, D. K. Understanding the Role of ETS-mediated Gene Regulation in Complex Biological Processes, Advances in Cancer Research, in press.



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