For delineating the fundamental mechanisms by which Ras oncogenes regulate cellular proliferation, survival, metabolism, and signaling, and for defining Ras-mediated modulation of these processes in pancreatic cancer initiation and progression.
A quintessential figure in cancer research, Dr. Bar-Sagi has significantly contributed to the understanding of the mechanisms driving pancreatic cancer development and progression. She is credited for demonstrating the role of Ras oncogenes in regulating cell proliferation, survival, metabolism, and signaling, and for providing fundamental insights into how Ras-mediated induction of these processes is responsible for carcinogenesis. Additionally, her RAS microinjection studies led to the observation of membrane ruffling, which subsequently provided the first direct link between RAS and macropinocytosis.
Dr. Bar-Sagi’s research has highlighted the crucial role of this endocytic process in tumor cell survival, specifically in pancreatic cancer cells harboring homozygous RAS mutations. She proved that extracellular proteins are capable of being internalized via micropinocytosis, then undergo proteolytic degradation, in turn providing the necessary amino acids to stimulate central carbon metabolism. These findings have since established macropinocytosis as an essential pro-survival mechanism for tumor cells and a biological mechanism with the potential to be exploited to facilitate drug delivery to cancer cells.
More recently, her work has demonstrated that mutant KRAS tumor cells contain increased numbers of protective stress granules and that this upregulation is dependent on the production of 15-d-PGJ2, a secreted lipid that provides a protective phenotype to neighboring tumor cells that do not contain KRAS mutations, rendering them resistant to chemotherapeutic therapies. This research continues to advance the understanding of pancreatic cancer biology and tumor fitness and has encouraged numerous research efforts devoted to the diagnosis and treatment of pancreatic cancer.
2018 AACR-Women in Cancer Research Charlotte Friend Memorial Lectureship
2016-2019 Board of Directors, AACR
2016 Outstanding Investigator Award, National Cancer Institute
2013- Present Board of Scientific Advisors, National Cancer Institute
2013 Lola & John Grace Distinguished Lectures in Cancer Research, Foundation ISREC, Lausanne, Switzerland
2009- Present Deputy Editor, Oncogene
2008-2010 Elected Chair, Scientific Advisory Board, Pancreatic Cancer Action Network
2006-2011 Board of Scientific Counselors, National Cancer Institute
1996-2006 Merit Award, National Cancer Institute