Our laboratory work examines the interface between cancer and developmental biology.
Our projects take advantage of mouse and cell culture-based models and a wide range of cell, molecular, and histological tools to understand how the Rb and p53 pathways influence aspects of cell and organ development – as a window into their anti-cancer effects.
In recent years, it has become increasingly clear that cancerous cells co-opt developmental mechanisms to achieve their full malignant potential. Their enhanced abilities includes the capacity to proliferate, migrate from one site to another, survive in harsh environments (for example, without being attached to a substrate or basement membrane or in hypoxic conditions), and foster angiogenesis.
Because a developing cell or organism uses these same mechanisms, the processes are under tight genetic control in the normal setting. Indeed, many of the so-called “tumor suppressor genes” found in the mammalian genome are most likely present because of the roles they play during development. By better understanding some of these pathways and the actions of individual tumor suppressor proteins in cell differentiation or tissue development, we can gain new insight into how the same proteins also impede cancer development or progression.
Rb and p53 tumor suppressor pathways
We focus on two key tumor suppressor pathways centered on the Retinoblastoma gene product, Rb, and the p53 tumor suppressor. Rb was once viewed rather simply as a “brake” for cell cycle progression from G1 to S phase of the cell cycle. Now, we know that it influences a wide range of processes in mouse embryo development by actions both intrinsic and extrinsic to cells.
The p53 tumor suppressor represents the working end of a genetic and biochemical pathway that senses and responds to a variety of oncogenic stressors – like ionizing radiation, UV radiation, or oncogene expression – to influence the expression or activity of other proteins driving such processes as DNA damage repair, cell cycle arrest, or apoptosis.