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MUHC researcher links self-defeating gene to lethal infections

Caspase-12 is a molecule with a death-wish. Found only in people of African descent, this protein shuts down our body’s immune system, opening the door to potentially lethal infections. In a groundbreaking new study published in the prestigious journal Nature this week, the team that first discovered the role of caspase-12 in humans has now uncovered the mechanism by which it sabotages us, allowing researchers to develop methods to counter its damaging effects.

Caspase-12 is found in around 20% of people of African descent, but was entirely lost from all other ethnicities around 60,000 years ago. "It’s a mystery why only African populations retained this enzyme," says Dr. Maya Saleh, a medical scientist in the Critical Care Division at the MUHC and assistant professor in the Department of Medicine at McGill University. "It’s possible that in Africa the protein could once have had a protective function fighting autoimmune diseases or perhaps parasites, like malaria; today caspase-12 provides no benefit to those who carry it, and often leaves the body more vulnerable to life-threatening infections and sepsis (’septic shock’). "Only by investigating the mechanisms by which caspase-12 works can we hope to inhibit its destructive effects," says Dr. Saleh.

Dr. Saleh and a research team from Merck and the La Jolla Institute for Allergy and Immunology in San Diego conducted laboratory experiments using mice deficient in the caspase-12 gene. "We discovered that caspase-12 blocks the body’s inflammatory response to infection by blocking the activity of another useful enzyme," says Dr. Saleh. "It’s kind of like the bad leading the good astray." Dr. Saleh’s discovery is a major step forward and will allow researchers to develop treatments that may help strengthen the immune system of those people unfortunate enough to have the caspase-12 gene product.

This research was funded by a fellowship from the Canadian Institutes for Health Research (CIHR), the MUHC and McGill University to Dr. Saleh.

The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, a university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 500 researchers, nearly 1000 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. For further details visit:

The McGill University Health Centre (MUHC) is a comprehensive academic health institution with an international reputation for excellence in clinical programs, research and teaching. The MUHC is a merger of five teaching hospitals affiliated with the Faculty of Medicine at McGill University--the Montreal Children’s, Montreal General, Royal Victoria, and Montreal Neurological Hospitals, as well as the Montreal Chest Institute. Building on the tradition of medical leadership of the founding hospitals, the goal of the MUHC is to provide patient care based on the most advanced knowledge in the health care field, and to contribute to the development of new knowledge.

Ian Popple | MUHC
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