The majority of my research career has been on understanding the role of the Ras oncogenes in malignancy and in this regard we were able to identify a novel member of the Ras family, M-Ras (Kimmelman et al., 1997). We went on to dissect the critical signal transduction pathways that were responsible for mediating its functions of promoting cellular survival and differentiation (Kimmelman et al., 2000; Kimmelman et al., 2002). This focus on Ras continued during my most recent efforts in studying pancreatic adenocarcinoma, a cancer that is nearly universally driven by a mutation in the Kras oncogene (Hezel and Kimmelman et al., 2006). In recent work, we have identified novel oncogenes in pancreatic cancer using a combination of genomic and functional approaches and have linked these genes to the invasive phenotype of this deadly. Additionally, we have established an inducible model of pancreatic adenocarcinoma that is phenotypically identical to the human disease. This model, driven by an inducible Kras oncogene will provide a platform for pre-clinical therapeutic testing as well as for in depth interrogation of the biology of the disease. We are currently utilizing this model to understand the role of Kras in terms of tumor initiation and maintenance.
A major focus of the lab is to identify defects in mitotic checkpoints and DNA repair pathways that can be exploited for therapeutic gain. Related to this, we are actively studying pathways involved in pancreatic cancer cell survival and metabolism to identify novel vantage points of attack.
Clinically, I am also a practicing radiation oncologist with a focus on gastrointestinal malignancies (20% of my time). During this time I am involved in supervising and teaching Radiation Oncology Residents as well as medical students that rotate through our department. I am also a faculty advisor for a resident run translational science group.