Scholar Profile

L. Charles Murtaugh

Assistant Professor
Department of Human Genetics
University of Utah
15 N. 2030 E. Rm. 2100
Salt Lake City, UT 84103
Voice: 801-581-5958
Email: murtaugh@genetics.utah.edu
Personal Homepage
2006 Searle Scholar

Research Interests

The pancreas is the site of two devastating diseases: type I diabetes, caused by autoimmune destruction of insulin-producing beta (b) cells, and pancreatic cancer, one of the deadliest human tumors. The former involves the endocrine islets of Langerhans, which comprise several hormone-producing cell types; the latter is thought to arise from the exocrine compartment, which normally produces digestive enzymes. By studying the development of these tissues, I hope to shed light on disease treatment and prevention.

I have begun my work by investigating the role of intercellular signaling pathways in the pancreas. Using conditional gene activation and deletion in mice, I have shown that the Notch and Wnt/b-catenin pathways play critical and distinct roles in the developing pancreas. Notch acts to arrest the differentiation of pancreatic progenitor cells, much as it does in the central nervous system. Further work in my laboratory will examine the role played in the pancreas by upstream activators and downstream targets of the pathway. Outside the pancreas, including the colon and central nervous system, a similar role in inhibiting differentiation has been ascribed to the Wnt/b-catenin pathway. However, abrogating this pathway in the pancreas does not result in premature differentiation; instead, endocrine development is relatively normal while exocrine cells are almost completely absent. Thus, the major role for this pathway appears to be in promoting exocrine development; I am interested in determining precisely when and how it acts, and whether it mediates a choice between endocrine and exocrine cell fates.

Human pancreatic tumors and precancerous lesions exhibit upregulation of Notch pathway components, as do analogous lesions in mouse models of the disease. By preventing the differentiation of precancerous cells, Notch may functionally synergize with other cancer-promoting signals. I am now testing whether Notch activation will accelerate disease progression in a mouse model of the disease. The Wnt/b-catenin pathway is hyperactive in colon and other cancers, but has been described as downregulated in pancreatic cancer. By preventing exocrine differentiation, Wnt/b-catenin downregulation might facilitate the expansion of precancerous cells. I am currently testing the effects of b-catenin activation or inhibition in the context of mouse pancreatic cancer lesions. In the future, I am interested in more directly examining the role of these and other developmental pathways in human pancreatic cancer, in primary tumor samples as well as cell lines.