Dr. Frank Sicheri — The Samuel Lunenfeld Research Institute

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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 a number of molecules, 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 and diabetes. His discoveries are critical to the development of new drugs that target these diseases.

In particular, Dr. Sicheri studies a family of enzymes called protein kinases. The human genome encodes approximately 500 protein kinases. These molecules act as switches within cells that regulate numerous biological processes. Malfunction of protein kinases – 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 cause cells to grow and multiply uncontrollably.

Scientists have found that the activity of protein kinases can be inhibited with specific 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 (Gleevac), and some forms of lung cancer (Iressa).

To date however, only a fraction of the protein kinases encoded in the human genome have been explored. Dr. Sicheri’s research is directed at improving our understanding of how protein kinases work, and at defining the structure and function of new kinases in order to unlock their potential as drug targets for disease. He has made a number of important discoveries in this area, including solving the structure of a kinase known to be active in colon cancer, and another that suppresses tumour formation.

Samuel Lunenfeld
Research Institute
Mount Sinai Hospital
Joseph & Wolf Lebovic Health Complex
600 University Avenue
Toronto Ontario M5G 1X5

Tel: 416-586-4800 ext.8471
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Jul 15, 2009 04:50 PM

At a Glance

Dr. Frank Sicheri is a ‘structural biologist’ who investigates the cellular basis of cancer, viral infection and diabetes.
Namely, he studies the structure and function of a family of enzymes called protein kinases. The human genome encodes approximately 500 of these special enzymes.
He uses a technology called protein crystallography – that uses high-powered x-rays to determine the structure of the proteins.
His research aims to lead to the development of anti-cancer drugs.

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 to determine the detailed structure of individual protein domains and their assembly into higherorder complexes. Structures that the Sicheri lab is working on are the catalytic domain of the Eph receptor tyrosine kinase, the SCF E3 ubiquitin ligase, the RNA dependent protein kinase PKR, the polo family kinase Sak and the protooncogene Akt.

Recent Publications

Mao DYL, Neculai D, Downey M, Orlicky S, Haffani Y, Ceccarelli DF, Ho JSL, Szilard RK, Zhang W, Ho CS, Wan L, Fares C, Rumpel S, Kurinov I, Durocher D, Sicheri F. Atomic structure of the KEOPS complex: an ancient protein kinase-containing molecular machine. (2008) Molecular Cell, 32, 259-75.

Lee K, Dey M, Neculai D, Cao C, Dever TE, Sicheri F. Structure of the Dual Enzyme Ire1 Reveals the Basis of Catalysis and Regulation in Nonconventional RNA Splicing. (2008) Cell, 132, 89-100.

Tang X, Orlicky S, Lin Z, Willems A, Neculai D, Ceccarelli DF, Mercurio F, Shilton BH, Sicheri F*, Tyers M*. Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination. (2007) Cell, 129, 1165-1176. *co-corresponding authors

► Lunenfeld Research Repository

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