Dr. Roderick McInnes

Director, Lady Davis Research Institute, Jewish General Hospital, Montreal; Alva Chair in Human Genetics, McGill University
Researcher of the month: 
Apr 2011

Since a fateful weekend caring for a patient dying of cystic fibrosis during his internship at Dalhousie University, Dr. Roderick McInnes hasn’t become one of the world’s leading medical geneticists by shying away from difficult questions.

In fact, having dedicated more than 30 years of his life to trying to understand and treat genetic diseases, he has been at the forefront of what is arguably the most dramatic period in the history of genetic research by taking on some of the most difficult questions in neuroscience including, in inherited neurodegenerations, why do neurons implicated in these diseases suddenly die after decades of normal function? 

The question is important because it is essentially the question regarding all inherited brain degenerations, whether it is inherited forms of Alzheimer’s or Parkinson’s disease, or retinal degenerations. These diseases are all characterized by a loss of neurons, the fundamental units for information transmission in the central nervous system.

“The retinal degenerations are like having Alzheimer’s disease of the retina,” explains Dr. McInnes. “If we knew what was going on between the birth of the mutant neuron, and its death decades later, we’d probably know how to stop the progression of these diseases.”

Dr. McInnes and his research team, previously at the Hospital for Sick Children at the University of Toronto and now at McGill’s Lady Davis Research Institute, have focused on using mice models to identify the molecular mechanisms that contribute to, or protect against the death photoreceptors in inherited retinal degenerations.  Photoreceptors are the light sensitive neurons in the retina that “catch” photons and in turn send nerve impulses to the brain, thereby telling the brain that you’ve seen something. When a mutation in a gene damages the photoreceptors in a retinal degeneration, the result is blindness.  

Surprising discoveries with major implications

Scientists working in the field of neurodegeneration had always assumed that in these diseases, the mutation led to a faster death of the cells due to accelerated wear and tear, compared to normal aging neurons. However, Dr. McInnes and his colleagues unexpectedly discovered that, at least in retinal degenerations, the cells don’t die of cumulative damage.

“In the retinal degenerations, we found that the risk of death is constant, rather than increasing with time” he explains. “Mutant retinal cells start dying right away, and the rate of death depends on the particular mutation.”
In addition to exploring retinal degenerations, Dr. McInnes has also identified several of the major genes that regulate eye development.  If these genes don’t function normally, the eye can be small – a condition called microphthalmia and abnormal in appearance, or it can appear normal but with defective connections between retinal neurons, resulting in blindness in either case. 

The discovery of genes that control connections between retinal neurons led Dr. McInnes to the surprising discovery of two “Neto” proteins which, as it turns out, play an important role in the brain’s synapses, or highly specialized sites of communication between the brain’s multitude of individual neurons. The strength of the communication at each synapse changes in response to neuronal activity – a process called synaptic plasticity – allowing networks of neurons to adapt and learn. 

“How synaptic plasticity occurs is a major question in neurobiology,” explains Dr. McInnes. “Our breakdown of the role of Netos in the brain adds to our understanding of a surprisingly broad range of fundamental neuronal processes.”

Amazingly, the Neto research team found that they could correct the learning and memory defects in mice lacking one of the Neto proteins with a drug. This remarkable finding established the principle that an inherited learning defect can be rescued with drugs, and that the learning defect wasn’t “hard-wired”.  “Hopefully”, says Dr. McInnes, “future research may make it possible to treat some human learning disorders, not just the one we induced in mice, with drugs as well”.

An ambassador of collaboration

Dr. McInnes is quick to point out that the eight-year Neto project was led by a talented graduate student, David Ng, and was accomplished via critical collaborations with other renowned researchers in Toronto, including neurophysiologist Michael Salter at the Hospital for Sick Children (SickKids) and John Roder, a neuroscientist at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital.

Dr. McInnes has, in fact, a well-earned reputation for forging common ground among fundamental researchers and clinicians, his dedication and enthusiasm for health research, his professional and inclusive approach, as well as his stalwart commitment to the field.  This has earned him many honours, including a 2008 appointment to the Order of Ontario and, in 2009, to the Order of Canada. Dr. McInnes is also a Fellow of the Royal Society of Canada and of the Canadian Academy of Health Sciences. He was the inaugural Scientific Director of the Institute of Genetics at the Canadian Institutes of Health Research (CIHR), and in 2010, the President of the American Society of Human Genetics.

His mission "to make a difference in a field that matters" hasn’t changed since his days as an intern at Dalhousie University, and Dr. McInnes is more committed than ever to helping other researchers reach their full potential.

“We simply must have faith, as individuals and as a society, in our ability to tackle big problems,” insists Dr. McInnes.  “Even though the feasibility of a project may be uncertain, humanity is fantastically inventive.”

Dr. McInnes’ research is currently funded by CIHR, a Tier 1 Canada Research Chair, and the Macula Vision Research Foundation of the US.

For further information, please contact Ms. Isabelle Fougnies using the Email contact form