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Last Updated: 7/20/2005
| William B Coleman, Ph.D.
Associate Professor |
Research Interests
The research in our laboratory involves several major projects related to the molecular pathogenesis of cancer, including (i) identification, isolation, and characterization of human liver tumor suppressor genes, (ii) investigation of the methylation-dependent epigenetic regulation of BRCA1 in sporadic and hereditary breast cancers, and (iii) investigations into molecular discrimination of multiple synchronous primary lung cancers.
Recent Accomplishments and Honors
Accomplishments:
We have identified three candidate liver tumor suppressor genes from human 11p11.2, have shown that these genes may be regulated by DNA methylation, and have linked the function of this tumor suppressor activity to the upregulation of other tumor suppressor genes, including WT1.
We have shown that approximately 30-35% of sporadic breast cancers lack expression of BRCA1 protein, possibly indicating a role for this gene in the genesis of these cancers. Continuing studies are examining the possibility that this loss of normal protein expression is due to methylation-dependent epigenetic regulation of the BRCA1 gene.
We have characterized the DNA methylation pattern of the BRCA1 tumor suppressor gene in suspected hereditary breast cancers from patients that lack mutations in BRCA1 or BRCA2. This observation forms the basis for examination of the possibility that a constitutional methylation defect results in a lack of normal expression of this and other genes that confer cancer susceptibility.
We have employed microsatellite PCR to examine allelic variability among multiple primary tumors in patients with head and neck and lung cancer, and in patients with multiple lung tumors, and have shown that the resulting genetic fingerprints facilitate determination of relatedness and lineage relationships. In this manner, we have shone conclusively that patients with smoking-related cancers tend to have multiple independently arising primary tumors, suggesting that these cancers are related to a field cancerization effect in the carcinogen-exposed epithelium.
Honors:
Joe W. Grisham Award for Excellence in Graduate Student Teaching, Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, June 2000
Joe W. Grisham Award for Excellence in Graduate Student Teaching, Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, June 2002
Distinguished Alumnus Award, Wingate University, Wingate, NC, October 2002
Publications
Ricketts, S.L., Garcia, N.F., Betz, B.L., and Coleman, W.B. (2002) Identification of candidate liver tumor suppressor genes from human 11p11.2-p12. Genes Chromosomes Cancer 33:47-59.
Rider, M.A., Butz, G.M., Ricketts, S.L., Newberry, S.T., Grisham, J.W., and Coleman, W.B. (2002) Suppression of tumorigenicity in rat liver tumor cells by human chromosome 13: Evidence against the involvement of pRb and BRCA2. Int. J. Oncol. 20:235-245.
Coleman, W.B and Tsongalis, G.J. (2002) Cancer epidemiology: Incidence and etiology of human neoplasms. In: The Molecular Basis of Human Cancer, W.B. Coleman and G.J. Tsongalis (eds.), Humana Press, Totowa, NJ, pp. 3-22.
Coleman, W.B and Tsongalis, G.J. (2002) The role of genomic instability in the development of human cancer. In: The Molecular Basis of Human Cancer, W.B. Coleman and G.J. Tsongalis (eds.), Humana Press, Totowa, NJ, pp. 115-142.
Ricketts, S.L., Carter, J.C., and Coleman, W.B. (2003) Analysis of known genes from human 11p11.2 identifies three candidate liver tumor suppressors. Mol. Carcinogenesis 36:90-99.
Jahn, J.E., Ricketts, S.L., and Coleman, W.B. (2003) Identification of candidate liver tumor suppressor genes from human 11p11.2 by transcription mapping of microcell hybrid cell lines. Int. J. Oncol. 22:1303-1310.
Furmaga, W.B., Ryan, J.L., Coleman, W.B., Cole, S.R., and Tsongalis, G.J. (2003) Alu profiling of primary and metastatic nonsmall cell lung cancer. Exp. Mol. Pathol. 74:224-229.
Coleman, W.B. (2003) Mechanisms of human hepatocarcinogenesis. Current Molecular Medicine 3:573-588.
Best, D.H., Butz, G.M., Moller, K., Coleman, W.B., and Thomas, D.B. (2004) Molecular analysis of an immature ovarian teratoma. with gliomatosis peritonei and recurrence suggests independence of multiple tumors. Int. J. Oncol. 25:17-25.
Coleman, W.B. (2004) Cancer bioinformatics: Addressing the challenges of integrated post-genomic cancer research. Cancer Invest. 22:169-171.
Coleman, W.B. (2005) Mechanisms of human hepatocarcinogenesis: An overview. In: Handbook of Immunohistochemistry and in situ Hybridization of Human Carcinomas. Volume 3: Molecular Pathology, Colorectal Carcinoma, and Prostate carcinoma. M.A. Hayat (ed.), Elsevier Science Press, Philadelphia, (In Press).
Coleman, W.B. (2005) Molecular mechanisms in human carcinogenesis. In: Cancer: Cell Structures, Carcinogens and Tumor Pathogenesis, L.P. Bignold (ed.), Birkhauser Publishing, Basal, (In Press).
Coleman, W.B and Tsongalis, G.J. (2005) Molecular pathogenesis of human cancer. In: Molecular Diagnostics, Second Edition, W.B. Coleman and G.J. Tsongalis (eds.), Humana Press, Totowa, NJ, (In Press).
Tsongalis, G.J. and Coleman, W.B. (2005) Clinical genotyping: Rapid interrogation of single nucleotide polymorphisms and mutations in the clinical laboratory. Clin. Chim. Acta (In Press).
E-mail: wbcolemn@med.unc.edu
Telephone: 919 966-2699
FAX: 919 966-5046
Address: Room 515 Brinkhous-Bullitt Building Chapel Hill, NC 27599-7525
URL: http://www.pathology.unc.edu/common/coleman.htm
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