Scientist profiles A-F
Sunnybrook Research Institute
2075 Bayview Ave., Room S2 36
Administrative Assistant: Sue Santillo
Phone: 416-480-6100, ext. 5504
- B.Sc., 1992, immunology, human biology and microbiology, University of Toronto, Canada
- PhD, 1999, immunology, U of T
- Postdoctoral fellowship, 2003, molecular and cell biology, University of California (Berkeley), U.S.
Appointments and Affiliations:
- Senior scientist, Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute
- Associate professor, department of immunology, U of T
- Fellow, Trinity College, U of T
- Natural killer cell and innate lymphoid cell biology
- Self-nonself discrimination in innate immunity
The innate immune system represents a front line of defense against cancer, infectious disease, and other pathogenic conditions. Natural killer (NK) cells are a subset of innate lymphoid cells (ILC) that play a key role in innate immune surveillance. Natural killer cells can detect and eliminate transformed, infected, transplanted, antibody-opsinized and ‘stressed’ cells. How NK cells achieve self-nonself discrimination requires an understanding of the molecular interactions they use to sense what is harmless or dangerous, and how these molecules assist in the decision to ignore or respond to a target cell under surveillance. Our lab primarily investigates major histocompatibility complex (MHC)-independent receptor-ligand interactions involving the NKR-P1:Clr (Klrb1:Clec2) recognition system. This paired recognition system includes both stimulatory (NKR-P1A/C/F) and inhibitory (NKR-P1B/D/G) receptors that recognize up- and downregulated Clr ligands on target cells. In addition, we recently developed an in vitro cell line model of ILC function (MNK-1/3, which resemble ILC1/3, respectively). This model allows for rapid analysis of gain- and loss-of-function genetics directly in ILC by gene overexpression, editing and deletion. The overall goal of the lab is to advance understanding of how receptor-ligand interactions and transcription factor networks affect innate immunity to cancer, infection and transplantation.
Dr. Carlyle studies the role of NK/ILC in self-nonself discrimination by innate immunity. Natural killer and ILC cell biology are central to cancer immunology in three ways:
- NK cells can recognize and destroy tumour cells directly.
- NK cells can sense and eliminate host cells infected with viruses, which frequently harbour or activate cancer-causing oncogenes.
- NK cells are clinically important in rejection of bone marrow transplants, a therapeutic intervention used in combination with chemotherapy and radiotherapy in the treatment of blood-borne cancers such as lymphomas.
In addition, NK cell biology directly impacts infectious disease research, as NK cells play an important role in the early immune response to foreign pathogens, especially viruses and intracellular bacteria. In fact, pathogens such as cytomegalovirus (CMV) have evolved intricate mechanisms to subvert NK cell recognition and innate immunity. The study of host-pathogen interactions can elucidate novel mechanisms of host innate immune recognition. Finally, insight into the role of NK cells in self-nonself discrimination can be gleaned from genetic studies involving models of allo- and xeno-transplantation.
To date, Dr. Carlyle has outlined roles for MHC-dependent (Ly49:MHC-I) and MHC-independent (NKR-P1:Clr) interactions in fighting cancer, infectious disease, transplantation and genotoxic stress. The lab studies the structure, function and regulation of NK/ILC receptor-ligand interactions, how pathogens can evade detection by NK cells, and how NK recognition affects rejection of bone marrow transplants. This knowledge could lead to therapies in cancer treatment, control of infectious disease, transplantation biology and perhaps autoimmunity.
Related News and Stories:
- Researchers find viral molecule that restrains immune cells: Critical discovery shows how viruses bypass the body's natural defenses (March 23, 2017)
- National agency recognizes scientific excellence at Sunnybrook Research Institute: Scientists score high with multimillion-dollar funding investment (Oct. 13, 2015)
- Bankrolling natural killers: Dr. James Carlyle scores big in recent round of funding announcements (Aug. 27, 2008)