In the early stages of my career, I discovered that the oncogenic potential of animal retroviruses depends on their Long Terminal Repeat (LTR), and I proposed the insertional mutagenesis model of oncogenesis. Following the validation of this model, my laboratory pioneered the use of insertional mutagenesis as a tool for the discovery of genes involved in the initiation and phenotypic progression of cancer. The list of genes we identified includes Akt, Tpl2, Gfi1, Gfi1B, KDM2B and others. The scope and the impact of this work are illustrated by the central role played by the kinase encoded by one of these genes (Akt) in Biology and Medicine. Following the initial characterization of Akt, we made the observation that the activity of the Akt kinase is regulated by PI-3-Kinase-generated D3-phosphorylated phosphoinositides, which function by binding to the Akt PH domain. This observation was followed by more than 100,000 publications to-date, linking the PI-3K/Akt pathway to cellular and organismal biology. Molecules identified via this research as regulators and targets of this pathway are among some of the most promising molecular targets for cancer and other human diseases to-date.

Currently, my laboratory uses the three Akt isoforms and some of their targets, Tpl2 and the histone demethylase KDM2B as probes to explore how signaling pathways regulate epigenetics, RNA processing, metabolism and immunity. Our goal is to use the results of these and other similar studies and systems methodologies, to interpret extend and exploit the information on the biology of human cancer, which is rapidly accumulating with the advent of new technologies. This goal is consistent with the philosophy that guided my lab through the years, which recognizes the value of the combination of systems-based strategies and in depth reductionist analyses.

Comments are closed, but trackbacks and pingbacks are open.