JERUSALEM — The discoveries made by scientist Howard Cedar may not lead to a cure-all cancer pill, but his research has yielded insights into the causes of cancer that could help identify those most at risk and offer them preventative care.
Howard Cedar
Cedar, head of the developmental biology and cancer research department at the Hebrew University of Jerusalem, spoke to a group of six Canadian journalists in June as part of a six-day tour in Israel sponsored by Canadian Friends of Hebrew University (CFHU), a non-profit group that promotes and raises funds for the school.
The American-born professor, a recipient of the 2008 Wolf Prize – one of Israel’s highest honours – first won scientific acclaim about 30 years ago when his research led to a new field of science called epigenetics, the study of changes in gene functions that occur without a change in the sequence of DNA.
Cedar’s findings provided scientists with clues as to how genes are regulated at the molecular level.
For his investigation into DNA methylation (chemical changes that occur in DNA molecules), Cedar has since been known as the “father of gene methylation,” and has discovered that methylation is involved in 95 per cent of cancer cases.
Cedar, considered Hebrew U’s best chance at another Nobel Prize, explained that when methylation occurs, the result is that only one part of the DNA code is available for the cell to read.
For example, a skin cell will only have genetic instructions to make skin, while the rest of its DNA code is “switched off.”
When an egg is fertilized, the first bundle of cells produced from it can develop into any cell in the body, because none of its genetic material has been methylated yet, he said.
But at some stage, the cells begin to assume particular functions – liver cells, skin cells, blood cells, etc.
“For example, the genes in liver cells are expressed, and proteins are made in the cell. Other genes in the liver cells are methylated. They are turned off in the liver cell,” Cedar said.
“So you could walk along the DNA, and say, ‘This is on, this is off, this is on, this is off.’ The reason the liver gets made the way it does is because of the way the switches are turned on… Is this going to be a liver, or is this going to be a kidney?”
This information is relevant to the study of cancer, because now, with scientists having the technology to thoroughly examine cancer cells, they’ve discovered that cancer is a kind of “switching disease.”
In other words, cancers form when genes that are supposed to be turned off are turned on, and vice versa.
He added that regardless of the kind of cancer, methylation occurs in almost every tumour.
In late 2008, Cedar and his Hebrew U colleague Yehudit Bergman identified the mechanism by which human cells assume particular functions. With that information, they learned that genetic diseases such as Fragile X Syndrome – the most common form of developmental disability – also result from a gene that’s been turned off that is supposed to be turned on.
“There is nothing wrong with the gene – the gene’s fine. We only need to find a way to turn that gene on, like a switch,” he said.
Based on research he conducted on mice that were genetically manipulated to develop colon cancer, he and his team discovered that if those same mice were given drugs to inhibit DNA methylation from birth, the disease could be prevented.
Cedar – who is also a researcher at the new Institute for Medical Research Israel-Canada (IMRIC), for which CFHU has pledged to raise $50 million – said that he’s pleased to be partnering with Canadian scientists, including McGill University’s Moshe Szyf.
It’s one example of the interdisciplinary partnerships made through IMRIC in the hope of giving scientists in various research areas the opportunity to work together to better understand and prevent diseases such as cancer, Alzheimer’s and Parkinson’s.
Cedar said he is excited about the potential that IMRIC provides and praised Canadian donors for “seeing the bigger picture” and realizing that supporting Israeli scientists means they, too, will benefit from any medical discoveries that come out of Israel.
“We are very lucky that the Canadians love us.”
