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| William K. Funkhouser Jr., M.D., Ph.D.
Associate Professor |  |
Clinical Interests
My service responsibilities include pulmonary, cardiac, pulmonary/cardiac transplantation, ENT, and GU surgical pathology, as well as molecular genetics.
Research Interests
Our laboratory is interested in developing rapid methods of obtaining genotypic and phenotypic data from frozen and formalin-fixed tissues, as well as the subsequent testing of these data as independent predictors of clinical outcome. We are currently interested in
1) mismatch repair gene expression and microsatellite instability in human colorectal adenocarcinomas, 2) correlation of mRNA and protein expression for known prognostic loci in non-small cell lung carcinoma, and 3) generation of stable, reusable solid phase cDNA libraries from laser capture microdissected specimens.
Colorectal carcinoma (CRC):
Lineberger Epidemiology grant funding 1999-2001 has allowed us to pursue study of the association between DNA mismatch repair defects and clinical outcomes in patients with CRC. We have developed immunohistochemical methods for the detection of the human mismatch repair proteins MSH6 and PMS2, and have acquired methods for the detection of the human mismatch repair proteins MSH2 and MLH1. Loss of expression of these proteins is being correlated with DNA microsatellite instability (an indicator of underlying mismatch repair defects) on a blinded sample of 250 UNC patients with sporadic CRC, following which the presence or absence of DNA mismatch repair defects will be correlated with clinical outcome differences.
Non-small cell lung carcinoma (NSCLC):
1) UNC Medical Alumni Endowment Fund grant funding has allowed us to begin to compare NSCLC prognostic gene expression at the RNA and protein levels. This will evolve into larger screening studies using microarray and quantitative PCR technologies, and could translate into methods by which molecular variables can be used to predict metastatic risk in NSCLC patients.
2) Lineberger Epidemiology grant funding 2000-01 has allowed a multidisciplinary group from UNC Pulmonary Medicine (Rivera), UNC Pathology (Funkhouser) and NIEHS Molecular Carcinogenesis (Slebos, Taylor) to continue airway screening (LIFE bronchoscopy) and molecular biology studies of squamous metaplasia and dysplasia in high risk smokers. These studies should translate into mechanisms for earlier detection of carcinoma in situ, and a better understanding of the natural history of airway dysplasia in smokers.
3) In collaboration with the Weissman lab (Pathology), we are initiating screening immunohistochemistry studies for loss of expression of BRG1, BRM, p16, and RB in primary lung carcinomas.
Prostate carcinoma:
GlaxoSmithKline Collaborative Research Program grant funding has funded collaboration with the Smith (Pathology) and Mohler (Surgery) labs, allowing us to initiate studies of the neovasculature of human prostate carcinoma allografts in nude mice.
Training
Vanderbilt University M.D. 1979
California Institute of Technology Ph.D. 1992
Board Certifications
Anatomic Pathology 1996
Publications
Funkhouser WK, Koop BF, Charmley P, Martindale D, Slightom J, Hood LE. Evolution and selection of primate T cell antigen receptor BV8 gene subfamily. Molecular Phylogenetics and Evolution 8:51, 1997.
Creager AJ, Maia DM, Funkhouser WK. Epstein-Barr virus-associated renal smooth-muscle neoplasm. Report of a case with review of the literature. Archives of Pathology and Laboratory Medicine 122:277, 1998.
Funkhouser WK and Warnke RA. Preferential Ig VH4.21 gene segment usage in particular subtypes of B-cell lymphoma detected by antibody 9G4. Human Pathology 29:1317, 1998.
Judson PL, Temple AM, Fowler WC, Novotny DB, and Funkhouser WK. Vaginal adenosarcoma arising from endometriosis. Gynecologic Oncology 76: 123-125, 2000.
Cogswell PC, Guttridge DC, Funkhouser WK, and Baldwin AS. Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. Oncogene 19:1123-1131, 2000.
Funkhouser WK, Kaiser-Rogers K. Significance of, and optimal screening for, HER-2 gene amplification and protein overexpression in breast carcinoma. Annals of Clinical and Laboratory Science 31:349, 2001.
Richardson MW, Funkhouser WK, Senior B, Weston BW. Spindle cell lesions of the head and neck mimicking rhabdomyosarcomas in children (in press, Pediatric Hematology and Oncology, 4 pp., 2001).
Reisman DN, Strobeck MW, Betz BL, Sciariotta J, Funkhouser WK, Yaniv M, Sherman L, Knudsen E, Weissman BE. Concomitant down-regulation of BRM and BRG1 in human tumor cell lines: Differential effects on Rb-mediated growth arrest and CD44 expression. (in press, Oncogene, 12 pp., 2001)
E-mail: Bill_Funkhouser@med.unc.edu
Telephone: (919) 966-7026
FAX: (919) 966-6417
Address: 304 Brinkhous-Bullitt Building, CB# 7525 Chapel Hill, NC
