My laboratory focuses how autophagy contributes to both epithelial homeostasis and cancer using both in vitro and in vivo models. Currently, our three main goals are: 1) determine the role of autophagy in epithelial cell survival and oncogenic transformation; 2) delineate the role of autophagy in tissue homeostasis and tumor formation in vivo; 3) dissect the biochemical functions of the molecules that control autophagy (called ATGs) to ultimately exploit this process for therapeutic benefit.

Ongoing Research:

Detachment-induced autophagy in epithelial cell survival and oncogenic transformation : Using both loss-of-function and gain-of-function strategies directed against ATGs, we are studying how autophagy influences epithelial cell survival during extracellular matrix detachment (anoikis), lumen formation in 3D glandular structures, and anchorage independent growth. We also use these experimental systems to investigate how autophagy influences oncogenic transformation by determining: 1) how well-known oncogene pathways regulate autophagy, and 2) whether changes in autophagy contribute to the cancer-promoting properties of these pathways.

Role of autophagy in tissue homeostasis and cancer progression in vivo: Over the longer term, my laboratory wishes to delineate how autophagy influences tissue homeostasis and cancer progression in mouse cancer models. We are currently creating mice containing conditional null mutant alleles of ATGs, allowing us to delete these genes in a tissue specific manner. We plan to use these mice to assess the role of autophagy in cancer progression by crossing with established mouse models of cancer.

Biochemical functions of ATGs: Despite widespread interest in exploiting autophagy for therapeutic purposes, we have much to learn about this process in mammalian cells and tissues. Autophagy is a tightly regulated by highly conserved gene products called ATGs. We are examining how these ATGs function in mammalian autophagy using cell biological and biochemical approaches.