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Lunenfeld-Tanenbaum Research Institute
Mount Sinai Hospital
Joseph & Wolf Lebovic Health Complex
600 University
Toronto, Ontario
M5G 1X5
Tel.: 416-586-4800 ext.8471
► Web of Science Researcher ID
F-8856-2013
Dr. Frank Sicheri
SENIOR INVESTIGATOR
Structural biologist Dr. Frank Sicheri is widely regarded as one of Canada's pre-eminent scientists in his field. He has made outstanding contributions to our understanding of the structure and function of signalling proteins, many of which are implicated in disease. His research is focused on cancer, but he has a number of projects involving molecules involved in viral infection, inflammation, and diabetes. His discoveries are critical to the development of new drugs that target these diseases.
In particular, Dr. Sicheri studies two families of signalling proteins called protein kinases and ubiquitin ligases. The human genome encodes approximately 500 protein kinases and over 600 ubiquitin ligases. These molecules act as switches within cells that regulate all biological processes. Malfunction of these proteins, which can happen as a result of genetic mutation or damage from a virus, gives rise to cellular dysfunctions that underlie numerous diseases. One common example is cancer, in which malfunctioning kinases and ubiquitin ligases cause cells to grow and multiply uncontrollably.
Scientists have found that the activity of protein kinases can be inhibited with specific drug-like molecules. As a result kinases have become an important focus by pharmaceutical companies in the development of new drugs. Drugs which inhibit specific kinases are already being used successfully to treat chronic myeloid leukemia (Gleevec), and some forms of lung cancer (Iressa). In contrast, the therapeutic potential of ubiquitin ligases as drug targets is largely untapped.
To date however, only a fraction of the protein kinases and ubiquitin ligases encoded in the human genome has been explored. Dr. Sicheri's research is directed at improving our understanding of how these proteins work by viewing them at atomic level resolution to unlock their potential as drug targets for disease. He has made key discoveries including most notably, uncovering the basis by which the RAF family kinases drive tumour formation and potential therapeutic strategies to reverse their adverse effects.
At a Glance
Dr. Frank Sicheri investigates the cellular basis of cancer, viral infection, inflammation and diabetes.
He studies the structure and function of two families of enzymes called protein kinases and ubiquitin ligases. The human genome encodes approximately 500 protein kinases and over 600 ubiquitin ligases, many of which are implicated in human disease.
He uses technologies called X-ray crystallography, nuclear magnetic resonance, and cryo electron microscopy to determine the structure of proteins at atomic resolution.
His research aims to facilitate the development of drugs to treat human disease.
Major Research Activities
Dr. Sicheri's lab is interested in the structure and function of protein kinase signaling molecules. His laboratory employs x-ray crystallography, nuclear magnetic resonance and cryo electron microscopy to determine the detailed structure of individual protein domains and their assembly into higher-order complexes. Structures that the Sicheri lab is working on include the protein kinases IRE1, RAF, NUAK2, MST1, and LATS1, and the ubiquitin ligases Cdc34 and Fbw7.
