Grant: Operating Grant

Patients suffering from a disease called Peutz-Jeghers Syndrome (PJS) have a high risk (>90%) of developing tumors, mainly in the stomach and intestine. Tumors can also develop at various other sites, including lung, breast, pancreas, uterus, ovary, cervix and testis. Most PJS patients have mutations in a gene called LKB1, indicating that this is the gene that causes the disease and therefore that the normal function of LKB1 is to prevent the formation of tumors. However, how LKB1 performs this function is unknown. The goal of this research proposal is to understand how LKB1 functions in normal cells, to gain insights into its role during tumor formation. To do this, I am using a small worm called C. elegans. The advantage of using C. elegans as a model is that it is very easy to manipulate and its cells behave like human cells; therefore understanding a gene's function in this animal can help us to understand what it does in humans. I am using modern cell biology, molecular biology and genetic tools to identify and characterize novel genes that can function with LKB1 to control the division of normal cells. This work will contribute to define the precise role of LKB1 in cell division. Because all of the genes that we study are conserved in humans, the discoveries that we make will help to understand how these genes function in human cells. As mutations in LKB1 are associated with a high risk of developing cancer, this work will also allow a better understanding of the molecular and cellular events that lead to the formation of tumors upon loss of LKB1 activity in PJS patients.