Prague, Czech Republic 2015: Scott Lowe

LoweSW ZRCPhoto

In 1990, we thought we understood cancer. It was a disease of cell proliferation and migration. Proliferation of mutated cells could be blocked by p53. Failure or mutation of p53 could be documented in half of all cancers. However, other arguments were beginning to appear. In 1991, Stan Korsmeyer published that the Bcl-2 protein, known for its activity in B-cell lymphoma, was reduced in cells that underwent apoptosis; in 1989 Peter Krammer realized that a specific protein, which he called Apo-1, could induce apoptosis in tumor cells; and in 1991 Shige Nagata recognized that the Fas-AntiFas system could induce apoptosis, with the synonymy of Apo-1 and Fas being recognized shortly thereafter. At this time Scott Lowe, working serendipitously with several doctoral mentors, recognized that functional p53 worked not only in the negative sense of preventing mitosis of cells with damaged DNA, it also worked in the positive sense of provoking apoptosis in those damaged cells that nevertheless initiated mitosis. The discovery, first published in 1993, led to a paradigm shift. Cancer was no longer a disease of unregulated cell replication. It also, and perhaps even mostly, was a disease or diseases in which cells failed to heed the normal physiological commands to die.

Since that time, Scott has led the field in research concerning p53 and especially its effect in controlling apoptosis as well as cell senescence. This research has led him to recognize that cells in which specific genes are permanently knocked-out or upregulated often compensate for the defect. He therefore has developed models in which genes can be temporarily and reversibly shut off. Using these models, as well as RNAi and mouse mosaic models, he and his group have pursued those few genes whose activity discourages tumor development. This has become an exciting new model for the study of the appearance of cancers, leading his group to study cancer genomics in samples from human patients. In these and other studies his group keeps generating new insights such as establishing that a therapeutic target could be translational control of cell survival. His laboratory has been the leader in combining cancer genomics, RNAi, and mouse models to undertake the functional annotation of the cancer genome.

Dr. Lowe received his Ph.D. at MIT and moved to Cold Spring Harbor Laboratory, where he remained for 15 years before moving in 2011 to Memorial Sloane Kettering Cancer Center, where he is a Howard Hughes Medical Institute Investigator, and Chair of the Cancer Biology and Genetics Program as well of the Geoffrey Been Cancer Research Center. He has won the AACR Award for outstanding achievement in cancer research, the MSKCC Paul Marks Prize for important contributions to the understanding of cancer, the Colin Thomson Memorial Medal of the International Association for Cancer Research, the Alfred G Knudsen Award of the National Cancer Institute, and many other awards. It is our pleasure and honor to recognize today his contribution to our understanding of how tumors are suppressed through apoptosis.