The judging committee of the 2016 Wolf Prize in Medicine unanimously decided that the prize will be awarded in two equal parts to two researchers: Professor Ronald Kahn, Harvard University,
For his pioneering contributions in the characterization of insulin action and its disruption in diseases. and Professor Lewis Cantley, Cornell University, for discovering the phosphoinositide-3 kinases and understanding their role in physiological conditions and diseases.
The judging committee of the 2016 Wolf Prize in Medicine unanimously decided that the prize will be awarded in two equal parts to two researchers: Professor Ronald Kahn, Harvard University, USA
For his pioneering contributions in the characterization of insulin action and its disruption in diseases. and Professor Lewis Cantley, Cornell University, USA for discovering the phosphoinositide-3 Kinases and understanding their role in physiological conditions and diseases.
Understanding the mechanism of insulin action and the processes that cause cell resistance to insulin are critical to cracking the pathogenesis of type 2 diabetes. Professor Ronald Kahn is a pioneer and leader in this field and contributed many original and important findings to the understanding of the field. His discovery, according to which the insulin receptor transmits signals through the activation of its own tyrosine kinase, was the first step in understanding the chain of responses in the cell to insulin. Later, the first target protein activated by the insulin receptor, called IRS-1, was identified and cloned in his laboratory. Kahn showed how the phosphorylation of IRS-1 leads to the activation of the enzyme (PI3K) phosphoinositide-3 Kinase and other signal transduction proteins, including many serine-threonine kinases, which Create an extensive network of cell signals through which the metabolic activities of insulin are mediated These served as a basis for understanding the pathogenesis of insulin resistance. At the same time, Kahn's clinical studies showed that insulin resistance precedes and leads to type 2 diabetes.
Later, Kahn's group created murine models of insulin receptor deficiency in various tissues using a conditional gene expression neutralization technique. These models have greatly contributed to understanding the action of insulin in classic target tissues of the hormone, such as liver and muscle, as well as in tissues that were believed to be less exposed to insulin resistance, such as brain and pancreas. Thus, for example, Kahn showed that in the liver different signals coming from the insulin receptor lead to differential effects in the metabolism of carbohydrates and lipids. He also discovered unique interrelationships between the body's resistance to insulin and the function of beta cells in the pancreas. These findings served as a springboard for many more human studies that outlined the current understanding of the pathogenesis of pre-diabetes and type 2 diabetes.
Over the years, Dr. Kahn has mentored an impressive number of research students and scientists who have greatly contributed to the current understanding of insulin's signaling actions.
Professor Lewis Canteli is known for his important contributions to the understanding of the signaling of growth factors, cellular metabolism, and their causal relationship to the development of cancerous tumors.
More than twenty-five years ago, Canteli discovered a key protein in signal transmission pathways called phosphoinositide-3 Kinase (PI3K). The discovery was based on a critical finding, showing that a protein that binds to the viral middle T oncogene in the polyoma virus phosphorylates phosphoinositides at position 3. This initial discovery by Cantli, which quickly turned out to be central to the signaling of tumor factor receptors and oncoproteins, led to a series of other discoveries by other researchers, many of them In collaboration with Cantli, one of them is related to the finding that the group Proteins carrying a segment with homology to the plekstrin protein, among them a key protein known as PKB, bind the phosphorylated lipid, phosphoinositide-3-phosphate, in the cell membrane, and thus their enzymatic action is activated. This action is essential and mediates the catalytic activity of growth factors in the cell. These are important findings , in addition to discoveries from other research groups, established the circumstantial relationship between the PI3K pathway and cancer. Although genetic defects in these pathways are very common in human cancers, for example, mutations in PI3K have been found in 30% of breast malignancies. Cantli's work has directly led to the development of new approaches to cancer treatment and the approval of several drugs that target this pathway. For the treatment of B-cell lymphoma patients, as well as for the development of drugs for other types of cancer, which are under evaluation clinical.
Another important aspect of Dr. Canteli's discoveries refers to the central role of PI3K in the mechanism of action of insulin. His group showed that PI3K mediates the response to insulin, the uptake of glucose and its metabolism in the cell, a discovery of great importance in the field of insulin action and diabetes. These findings led to an understanding of the control of Glucose levels under physiological conditions by insulin, and how this activity is impaired in type 2 diabetes XNUMX.
In later work, Dr. Canteli discovered that, unlike normal cells, cancer cells use the embryonic version of the glycolytic enzyme pyruvate kinase to channel the products of glucose metabolism into metabolites that catalyze efficient cell growth, instead of generating ATP. Canteli's group also contributed to the understanding of the control of Pathways activated by the kinases LKB1/AMPK, which has been proven to be central In Cancer Biology, Glucose Metabolism and Diabetes.
For all these, they will be awarded the Wolf Prize in Medicine for 2016.
