MEMORIAL UNIVERSITY
Disease triggers? Canada Research Chair using genome analytics to fight colorectal cancer, Alzheimer's

Part of an ongoing series of Gazette stories celebrating researchers who received support as part of a major investment by the federal government in science and research on June 14.

Dr. Touati Benoukraf envisions his lab as more than just a research space.

The recently renewed Canada Research Chair in Bioinformatics for Personalized Medicine sees it as a dynamic hub where the worlds of computational sciences, mathematics, medicine and clinical practice intersect.

And it's his job to bring everyone together.

Blueprint of life

Bioinformatics is a subdiscipline that uses computer technology to collect, store, analyze and disseminate biological data and information.

Dr. Benoukraf is particularly interested in data that describe the genome the blueprint of life encoded in our DNA and how mutations and structural variants influence disease.

Dr. Benoukraf is developing bioinformatics tools to generate and analyze DNA sequences and epigenetic processes that can trigger disease. Photo: Rich Blenkinsopp

"With a DNA sequencer, we can generate data on DNA sequences and epigenetic processes that affect the way DNA functions without changing its sequence, which can be induced by external influences including your lifestyle," said Dr. Benoukraf, an associate professor in the Faculty of Medicine. "Over the years, as you age, this accumulation of change can predispose someone to develop a disease. What I am trying to do is make sense of all this data to understand how people are predisposed to develop a disease or how they predispose themselves to it."

Dr. Benoukraf says a person's predisposition to disease is not fated and that most predispositions need a trigger.

"We're dedicated to understanding the mechanisms that activate that transition from predisposition to disease onset," he said.

Currently, he is trying to generate the maximum data possible and integrate that with data already available.

Dr. Benoukraf says that many labs put their data online, so he and his team are developing bioinformatics tools to analyze the data and databases to integrate all of it.

The age of artificial intelligence means they can reveal hidden patterns and insights to uncover new mechanisms and make discoveries.

N.L.-specific mutations

Dr. Benoukraf has chosen to focus on colorectal cancer, as rates are higher in Newfoundland and Labrador than anywhere else in the world.

"I'm involved in the Marathon of Hope Cancer Centres Network through the Atlantic Cancer Consortium and I'm the co-head of a project which aims to sequence 200 local patients with colorectal cancer," he said. "We are trying to map, not only the genetic landscape but also the epigenetic."

Previous studies into colorectal cancer in this province have identified mutations specific to the Newfoundland and Labrador population, but as with every disease, genetics cannot explain everything.

"The best way to cure cancer is to work on prevention." Dr. Touati Benoukraf 

One of their hypotheses is that external factors, such as environment or lifestyle, may play a critical role in initiating or triggering the disease.

Since the microbiome is highly influenced by external factors like diet, pollutants and overall lifestyle, we are also investigating the microbiome of a subset of patients analyzing both tumor and stool samples to explore the potential of identifying microbial imbalances as non-invasive predictors of disease development.

"The best way to cure cancer is to work on prevention being able to say to someone, you are on your way to predispose yourself, it's time to change something in your lifestyle," Dr. Benoukraf said.

Dr. Touati Benoukraf, centre, with his lab group at the Faculty of Medicine.

In the six years he has been at Memorial, he has continued collaborations with colleagues at the National University of Singapore, and École normale supérieure of Paris, which has benefited him, his students and local collaborators.

While partnering on a project looking for genes that trigger epigenic changes during aging, which can also predispose people to disease, they found new mechanisms that are a signature of Alzheimer's disease.

That connected Dr. Benoukaf to neurological researchers at Memorial who also want to work with him on this area.

Together they were able to obtain a $1 million Canadian Institutes of Health Research grant to study the molecular mechanisms underlying the complex interplay between genomics (the study of genes and DNA) and epigenomics (the study of chemical modifications that regulate gene activity) in Alzheimer's disease and colorectal cancers.

"Most of the molecular mechanisms for these diseases are actually the same," he said. "All of the bioinformatics tools that we are developing can be used on one or the other."