Franklin & Marshall College

 A model system to study the tumor suppressor APC and its role in Wnt regulation

To properly orchestrate the dramatic events that occur during development, it is essential that cells communicate with their neighbors through the use of cell signaling pathways.  While many of these signaling pathways play critical roles in the development of an organism, inappropriate activation of these pathways frequently results in cancer.

The Wnt signaling pathway is one such pathway that contributes to both normal development and cancer.  Wnt signaling plays essential roles in development such as defining cell fate decisions.  However, loss-of-function mutations in an important molecular player of the Wnt pathway called Adenomatous Polyposis Coli (APC) inappropriately activate the pathway and frequently lead to cancer.  In fact, mutations in APC are responsible for most cases of the inherited colon cancer syndrome, familial adenomatous polyposis, and overall are responsible for greater than 80% of all colon cancer cases.  Therefore, understanding APC’s function in Wnt signaling is crucial to understanding how it contributes to cancer.

It is now clear that APC participates in Wnt signaling by contributing to a multi-protein complex, called the “destruction complex.”  Despite intense interest in APC and Wnt signaling in general, the molecular role of APC in the destruction complex remains unknown.  My current work uses both fruit flies and cultured colon cancer cell lines to explore APC’s mechanism of action.  Potential projects in the lab include:

• defining the pieces of APC that are essential for its function in Wnt signaling
• identifying novel protein partners that work with APC
• investigating how APC interacts with known members of the destruction complex. 

These projects will address current models of APC function, and may ultimately help other researchers design better therapeutics to treat colon cancer.  I am looking for motivated, enthusiastic students to join my research group, and encourage students interested in conducting independent research in my lab to contact me.