Administrative Assistant: Meredith Maloney
Phone: 416-480-6100, ext. 7897
Email: meredith.maloney@sunnybrook.ca

Education:

• B.Sc., 1992, Immunology and Microbiology, Trinity College, University of Toronto, Canada
• PhD, 1999, Immunology, University of Toronto, Canada
• PDF, 2003, Molecular and Cell Biology, University of California (Berkley), USA

Appointments and Affiliations:

• Scientist, molecular and cellular biology - Odette cancer research program, Sunnybrook Research Institute
• Assistant professor, department of immunology, University of Toronto
• Fellow and senator, Trinity College, University of Toronto

Research Focus:

• Natural killer cell biology
• Self-nonself discrimination in innate immunity

Research Summary:

The innate immune system represents a front line of defense against neoplasms, infectious disease and other pathogenic conditions. Natural killer (NK) cells are innate immune lymphocytes that play a key role in innate immune surveillance. NK cells can detect and destroy cancer cells, cells infected with bacteria and viruses, tissue transplants and other target cells. Understanding how NK cells mediate target cell recognition at the molecular level is a fundamental question of NK cell biology. Intrinsic to this understanding is a knowledge of how the mature NK cell repertoire is generated and shaped during NK cell development, how NK cells use surface receptors to sense what is harmless or dangerous and how receptor–ligand interactions assist NK cells in the decision to ignore or kill a potential target cell.

Dr. Carlyle studies the role of NK cells in self–nonself discrimination by the innate immune system. NK cell biology is central to cancer immunology in three ways:

1. NK cells can recognize and destroy tumour cells directly
2. NK cells can sense and eliminate host cells infected with viruses, which frequently harbour or activate cancer-causing oncogenes
3. NK cells are clinically important in rejection of bone marrow transplants, a therapeutic intervention used in combination with chemo/radio-therapy in the treatment of blood-borne cancers such as lymphomas

In addition, NK cell biology impacts pure infectious disease research, as NK cells play an important early role in the immune response to foreign pathogens, especially viruses and intracellular bacteria. In fact, many pathogens have evolved intricate means of subverting NK recognition and innate immunity.

Finally, insight into the role of NK cells in self–nonself discrimination can be gleaned from genetic studies involving models of allo/xeno-transplantation.

To date, Dr. Carlyle has outlined roles for MHC-dependent (Ly49:MHC I) and MHC-independent (NKR-P1B:Clr-b) interactions in fighting cancer and infectious disease. He is currently studying the structure, function and control of NK receptor and ligand expression, how pathogens can evade detection by NK cells and how NK recognition impacts rejection of bone marrow transplants. This knowledge could lead to therapies in cancer treatment, control of infectious disease, transplantation biology and perhaps autoimmunity.

Selected Publications:

See current publications list at PubMed

Related News and Stories:

• Young, Bright and Honoured: Three Sunnybrook students receive Vanier Awards (June 26, 2009)
• Backrolling Natural Killers: Dr. James Carlyle scores big in recent round of funding announcements (August 27, 2008)
• Unique Interaction in Immunity to Infection, Study Shows (April 26, 2007)

Related Links:

• U of T profile - department of immunology