Randall F. Holcombe
Hematology/Oncology, School of Medicine
Phone: (714) 456-5153
Email: rholcomb@uci.edu
http://www.faculty.uci.edu/profile.cfm?faculty_id=5192
Randall Holcombe
Dr. Holcombe is a clinician scientist who is conducting research related to Wnt signaling in colon cancer. Aspects of this signal transduction pathway were being studied at UCI in Drosophila by Dr. Larry Marsh and in vitro in mammalian systems by Dr. Marian Waterman. Dr. Holcombe directed a collaborative program, which provided a translational, disease-oriented focus to Dr. Marsh and Waterman’s ongoing programs along with initiating an independent line of investigation in his laboratory. Their research has focused on non-APC components of the Wnt pathway and their alterations, and importance, in the pathogenesis of colon cancer. They were the first to define the critical importance of LEF1 in colon cancer and they defined the expression of Wnt ligands and frizzled receptors in both normal and malignant colonic mucosa. They also defined the role of Wnt signaling in the homeostasis of colonic stem cells and the regulation of expression of novel components of the pathway in the human colon. These studies suggest that components of the Wnt pathway may be utilized as diagnostic or prognostic markers in colon cancer. These studies will provide a foundation of knowledge necessary for the development of Wnt pathway-targeted therapeutic interventions.
Translational studies in Dr. Holcombe’s laboratory have also expanded to the investigation of Wnt signaling in other malignancies including melanoma and breast cancer.
Selected Publications:
Gatcliffe, T. A., Monk, B. J., Planutis, K., and Holcombe, R. F. (2007). Wnt signaling in ovarian tumorigenesis. Int J Gynecol Cancer.
Planutis, K., Planutiene, M., Moyer, M. P., Nguyen, A. V., Perez, C. A., and Holcombe, R. F. (2007). Regulation of norrin receptor frizzled-4 by Wnt2 in colon-derived cells. BMC Cell Biol 8, 12.
You, X. J., Bryant, P. J., Jurnak, F., and Holcombe, R. F. (2007). Expression of Wnt pathway components frizzled and disheveled in colon cancer arising in patients with inflammatory bowel disease. Oncol Rep 18(3), 691-4.
Zell, J. A., McEligot, A. J., Ziogas, A., Holcombe, R. F., and Anton-Culver, H. (2007). Differential effects of wine consumption on colorectal cancer outcomes based on family history of the disease. Nutr Cancer 59(1), 36-45.
You, J., Nguyen, A. V., Albers, C. G., Lin, F., and Holcombe, R. F. (2008). Wnt pathway-related gene expression in inflammatory bowel disease. Dig Dis Sci 53(4), 1013-9.
Chang, K. J., Lee, J. G., Holcombe, R. F., Kuo, J., Muthusamy, R., and Wu, M. L. (2008). Endoscopic ultrasound delivery of an antitumor agent to treat a case of pancreatic cancer. Nat Clin Pract Gastroenterol Hepatol 5(2), 107-11. |
