Research Interests
Our laboratory is broadly interested in elucidating mechanisms of growth and differentiation. We are particularly interested in the identification and functional characterization of genes influencing an individual's innate susceptibility to the development of colorectal cancer (CRC) and in the biological role of the Erbb/Egfr gene family.
In western societies, familial forms of CRC account for less than 10% of cancer cases. The vast majority of the remaining cases of arise sporadically in individuals thought to have an environmentally-influenced genetic predetermined susceptibility. Using the azoxymethane (AOM) carcinogen mouse model, we are pursuing a series of experiments to address the mode by which resistance/susceptibility to sporadic CRC is determined and to identify the genes that are involved in the process. The global approach we are taking to cancer modifiers is to use genetics for modifier detection and regional mapping. Concurrently, we are gathering detailed molecular and proteomic data about the changes occurring during tumorigenesis as normal colonic epithelium progresses to adenomas and eventually to carcinomas.
In vitro studies have identified numerous molecules that appear to be important for CRC development. One of these is the epidermal growth factor receptor (Egfr) which has long been circumstantially linked to CRC development. Using the Apc model of intestinal neoplasia and the Egfr hypomorphic allele in mice, we have definitively shown the dependence of early tumor expansion on normal Egfr signaling in vivo. We are currently investigating the mechanism by which Egfr acts to allow early initiated intestinal tumors to become established.

Recent Accomplishments and Honors
V Foundation Scholar
March of Dimes Basil O'Conner Award

Training
PhD (Genetics), Texas A&M University
Post-doc, Case Western Reserve Univeristy

Publications
Roberts RB, Threadgill DW. 2004. Modeling the entire patient: predicting side-effects of targeted therapies with the genetically engineered mouse. Cancer Cell 5:115-120.

Strunk K, Amann V, Threadgill DW. 2004. Phenotypic variation resulting from a deficiency of epidermal growth factor receptor in mice is caused by extensive genetic heterogeneity that can be molecularly partitioned. Genetics, In press.

Lee D, Cross SH, Strunk KE, Morgan J, Jackson IJ, Threadgill DW. 2004. Wa5 is encoded by a novel ENU-induced anti-morph allele of the epidermal growth factor receptor. Mammalian Genome, In press.

Lee D, Pearsall RS, Das S, Dey SK, Godfrey VL,Threadgill DW. 2004. Epiregulin is not essential for development of intestinal tumors but is required for protection from intestinal damage. Gastroenterology, In press.

E-mail: dwt@med.unc.edu
Telephone: 919-843-6472
FAX: 919-966-3292
Address: MBRB, Room 4340 Chapel Hill, NC
URL: http://www.mouselab.org

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