Dr. Frank Sicheri

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.