“Prof. Kimchi is all that an Israel Prize laureate ought to be – innovating, brilliant, someone who breaks new ground and overturns conventions,” Israel’s Education Minister Naftali Bennett tweeted upon announcing that Prof. Adi Kimchi of Weizmann Institute of Science’s Molecular Genetics Department would be awarded the 2019 Israel Prize for Life Sciences. “For years, she has worked to advance women in science and strengthen the standing of Israel’s academia in the world,” he added.
Kimchi’s work has focused on the fateful decision numerous cells face in the course of fetal development and in a variety of diseases: to die or not to die. “Kimchi is one of the pioneers in deciphering the mechanism of programmed cell death in mammals,” the Prize committee wrote. “She has developed pioneering approaches to deciphering, in human cells, this complex pathway, which directly affects normal development, as well as cancer. Her work has revealed innovative systemic molecular mechanisms for understanding the process of cell death at the level of protein production and disintegration.”
Prior to the 1990s, most of what was known about genes responsible for programmed cell death had come from studies of invertebrates. Kimchi developed an original approach to identifying such genes in mammalian cells. She showed that by exposing cells to stressful conditions in a laboratory dish and randomly neutralizing certain messenger molecules called mRNAs, it’s possible to identify genes playing key roles in programmed cell death. This research formed the basis for a pioneering “gene hunting” method and enabled Prof. Kimchi herself to identify a group of key cell death genes called DAPs, the best known of which is the tumor suppressor DAP-kinase. The discovery of DAPs, picked up by hundreds of research teams, is today considered one of the major milestones in programmed cell death research.
Kimchi’s team further discovered that in cancer, the tumor suppressor DAP-kinase sometimes stops working not because it contains mutations, but because it is “silenced” via an epigenetic mechanism: the attachment of a small chemical tag, a methyl group, to its promoter region. In follow-up studies conducted at cancer centers around the world, DAP-kinase was found to be silenced in this manner in a variety of leukemias, lymphomas and solid cancerous tumors. Moreover, the discovery of the epigenetic silencing method itself led to the development of diagnostic and prognostic markers commonly used in the clinical management of cancer.
Years of research into DAPs led Kimchi not only to identify new biochemical pathways of cell death but also to make new revelations about autophagy, a cellular recycling process that maintains body tissues in good order. She was among the first scientists to suggest that cells may deal with emergency situations via an interplay between programmed cell death and autophagy mechanisms, and came up with the idea of “double agent” proteins that can take part in both these processes. These studies led to a systemic way of looking at the more than a hundred cell death and autophagy proteins known today. They have also facilitated the search for vulnerable spots in complex protein networks that may be targeted in order to block or accelerate cell death, depending on therapeutic needs.
In addition to noting Prof. Kimchi’s scientific achievements, the Prize committee also acknowledged her “long-standing contribution to promoting young scientists and women in science.” She has been active in advancing this cause throughout her scientific career and in the past served as Weizmann Institute’s President’s Advisor for Advancing Women in Science.
Prof. Adi Kimchi's research is supported by the Helen and Martin Kimmel Institute for Stem Cell Research. Prof. Kimchi is the incumbent of the Helena Rubinstein Professorial Chair in Cancer Research.