Aaron Goodarzi was a little lost when he returned home to Calgary. It was late in 2010 and he had spent nearly six years on the south coast of England completing a post-doctoral fellowship at the Genome Damage and Stability Centre at the University of Sussex.
During the time Goodarzi was away, Calgary, the city he grew up in after his family emigrated from Northern England, had multiplied like bacteria in a warm and humid environment. The population had increased by more than 10 per cent and eclipsed the one million mark. The University of Calgary, where Goodarzi grew up academically, had kept pace with its city.
“I left knowing every single nook and cranny of this place and returned getting lost, chronically, for the first month because there were so many new buildings that I had just never seen,” the 35-year-old recalls from his office at the Heritage Medical Research Building at the U of C’s faculty of medicine.
Goodarzi had to get reacquainted with his alma mater in a hurry. To do this, he joined the University of Calgary Southern Alberta Cancer Research Institute as an assistant professor in 2011. He’s now settling in as the new Canada Research Chair in Genome Damage and Instability Disease.
Recently, the chair received $500,000 for a five-year federal government grant. The funding will be used to study the impact that environmental factors like radiation exposure have in damaging DNA strands and why those damaged chromosomes are susceptible to cancer.
“Every species on this planet is pretty good at repairing DNA damage. As we age, the system breaks down a bit and we repair it incorrectly, or not at all,” Goodarzi says. “Using various tricks of our trade, we can look at where the DNA damage is and how it is repaired over time, if it is repaired over time and what type of genetic abnormalities it results in.”
Down the hall, a few doors from Goodarzi’s office, normal cells and cancer cells sourced from biopsies and packaged in artificial blood are growing in four incubators, each the size of a mini-refrigerator. Goodarzi and his team then analyze the cells at a sub-nuclear level using two microscopes that Goodarzi received in association with his national research chair.
“That is now our high-resolution microscopy facility, which we are using to image DNA breakage and repair in a laboratory setting,” he says. “We’ll use this to investigate alpha particle radiation and the genetic risk factors that may be present to predispose people to aging and genetic instability.”
Goodarzi developed an affinity for genome damage and radiation biology while completing a biochemistry bachelor’s degree at the U of C. At the time he was contemplating the choice of becoming a clinician or scientist. However, after a seminar presented by Dr. Susan Lees-Miller, Goodarzi decided to change his career path to the laboratory and medical science.
In the seminar, Lees-Miller, holder of the Alberta Cancer Foundation-Engineered Air Chair in Cancer Research at the U of C, talked about a protein called Ataxia Telangiectesia Mutated (ATM) that is linked to a devastating childhood immune deficiency, which leaves patients cancer-prone and extremely sensitive to radiation. It turns out ATM is similar to a protein Lees-Miller discovered a few years earlier called DNA-PK, which Goodarzi thought was “the coolest thing in the world.” He told Lees-Miller as much after the seminar and joined her lab in May of 1999 and became a full-time PhD student in September that same year.
“He was an excellent PhD student and did a fantastic job in his post-doctoral research in the U.K.,” Lees-Miller says, adding that his work was included in some seminal published papers regarding DNA damage and repair that were a significant breakthrough in the field.
Genome stability research was established in the 1980s, possibly earlier, says Goodarzi, but its popularity took off in the 1990s and is an active field around the globe.” At about 25 years, still we’re a relatively new-ish field by comparison to some others,” he says.
In March of this year, a symposium on genomic instability and DNA repair in Banff attracted more than 600 attendees who study the topics and how they relate
“Every cancer cell shows genomic instability where the chromosomes are not rejoined properly,” says Lees-Miller. “We want to understand the process, how it starts, what’s involved and find ways to prevent genomic instability.” She says researchers would also like to exploit any weakness in cancer cells to find better ways to kill tumours.
Lees-Miller says that cells with mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 have been found to be sensitive to inhibitors of a genomic instability protein called PARP. In less than five years of those findings, the first clinical trial was performed and, she says, currently more than 85 clinical trials around the world are testing PARP inhibitors for treatment of cancer patients. “In certain areas we’ve seen incredible advances in the last 10 years, and we’re able to exploit the genetic weaknesses in these tumour cells as well as using these small molecule inhibitors – basically new drugs – to target those particular cancers,” she says.
Goodarzi is particularly interested in lung cancer. More specifically, researching the correlation between lung cancer and radiation related to radon gas exposure. “What most people think about is X-rays or gamma rays, but people don’t realize that’s a small fraction of what we’re exposed to,” Goodarzi says. “Most of it is alpha particle radiation. Where does that come from? Basically, it’s all radon gas.”
A two-year study from Health Canada that was completed in 2012 on radon concentrations in homes found that no part of the country is radon-free and about 6.9 per cent of Canadians are living in homes with radon levels above the guideline of 200 becquerels (Bq) per cubic metre (a common measurement of radioactive material). Radon, a colourless, odourless and tasteless gas, accumulates in well-insulated homes built on uranium-rich soil and some of the highest concentrations from the federal study were found in the Prairies and the Maritimes.
Another study from Health Canada linked high levels of prolonged radon exposure to 16 per cent of lung cancer deaths in Canada. According to Lung Cancer Canada, an estimated 24,200 people in the country were diagnosed with lung cancer in 2010, which is more than any other kind of cancer diagnosis in Canada.
“The first time most people realize they have had a serious dose of radon is when they walk into a clinic never having smoked and are diagnosed with lung cancer – that’s too late,” Goodarzi says. “Non-smoker lung cancer, I would argue, is perhaps the most preventable. Nobody is addicted to radon.”
Through the Canada Research Chair in Genome Damage and Instability Disease, Goodarzi and his research lab, complete with international students, hope to identify genetic risk factors that cause only some people living in a house with high concentrations of radon to develop lung cancer, not all.
“We also would like to map, in a much more scientific and rigorous way, where the radon risk areas and hotspots are in this province,” Goodarzi says. “In the Calgary Health Region, Health Canada found 8.1 per cent of homes were over the minimum safe guideline, but that study only surveyed 89 homes. We would like to survey thousands of homes in the major population centres and get a handle on new and old communities.”
It’s possible that the national research chair could be renewed for another $500,000 and five years. Goodarzi has a long-term goal of discovering diagnostic markers, so people who have been exposed to a significant dose of radon-related radiation can be identified early.
“The Alberta government and the Alberta Cancer Foundation have the goal of a cancer-free Alberta. That’s a very far-reaching and laudable goal,” Goodarzi says. “We could eliminate radon-induced lung cancer within two generations if we identify and remediate all houses in this region with high radon gas levels.” He believes that by knowing the risk factors, generating a diagnostic approach, then remediating the houses, lung cancer in Canadians could be reduced by about 3,500 cases per year.
Goodarzi recently became a homeowner himself. He purchased a radon detector and placed it in his basement, but he missed the ideal middle-of-winter period for measuring radon when windows and doors tend to stay shut and radon gas is trapped inside. You need a 90-day period somewhere between November and March to provide the most comprehensive results.
He’s prepared to do the remediation work, which he says is similar to installing a sump pump in the basement to recycle the air, but he won’t know his home’s radon levels until next spring. By the time his results come in, he suspects almost everyone he knows will also have their own tests done, “because I talk about it so much.”