My research is focused on signal transduction pathways in cancer cells, and ways of treating cancer based on these pathways. The Ras pathway has been my primary interest. My lab is attempting to understand how oncogenic Ras alters cell growth and survival in cancer cells, and in cells from patients suffering from neurofibromatosis. The latter disease is caused by loss of a negative regulator of Ras of the Ras GAP family, a family of enzymes that was discovered in my lab. Loss of the neurofibromin protein leads to hyperactivation of Ras in cells of neural crest origin: as a result patients expressing defective neurofibromin suffer from learning defects, multiple benign lesions and an increased risk of certain cancers. We are using a combination of yeast genetics and biochemistry to understand more about the function of neurofibromin and how it is regulated, as well as new ways of treating this terrible disease.
My lab has also analyzed the wnt signaling pathway, the RB pathway and the p53 pathway. I am particularly interested in the role of the RB protein in cell differentiation and proliferation and the consequences of RB loss in breast cancer. We have analyzed ways in which the RB pathway is regulated in cancer cells, and have investigated the role of CDKs in cell proliferation. Also in the area of breast cancer research, we are investigating mechanisms of metastasis and of resistance to targeted therapies.
My interest in p53 is based on my proposal to use adenoviruses to kill cancer cells selectively based on loss of p53 in these cells. The lab is actively working on this principle and on ways of making viral therapy more effective, including ways of re-targeting adenovirus to cancer cells and a detailed analysis of RNA export and heat-shock related responses in cancer cells and cells infected with adenovirus.