Reversing Gene Damage in Cancer:

Dr. Paola Marignani aims to restore cells’ ability to fight cancer after DNA damage

Our bodies have built-in anti-cancer protein factories in every cell. Known as ‘tumour suppressor genes,’ they produce proteins that work together with other families of proteins to prevent more than 300 varieties of cancer. The DNA of tumour suppressor genes is, however, vulnerable to damage – and when this happens, we are vulnerable to cancer.

Dr. Paola Marignani, associate professor in the Dalhousie Medical School's Department of Biochemistry & Molecular Biology, is studying how tumour suppressor genes function in both healthy and cancerous cells, so she can identify the protein signalling events that are disrupted when DNA damage occurs.

“Tumour suppressor genes are gatekeepers that prevent tumours from forming…when they’re functioning, you don’t get cancer,” Dr. Marignani explains. “Damage to the DNA of these genes impairs their ability to produce tumour suppressor proteins, leading to a breakdown in the cell’s surveillance machinery. Eventually, malignant cells reproduce uncontrollably and cancers are formed.”

Dr. Marignani – who joined Dalhousie Medical School in 2003 following stints at the Ontario Cancer Institute and Harvard Medical School – hopes to pinpoint steps in the protein signalling process that are altered following DNA damage. This knowledge could lead the way to improved cancer detection methods and treatment therapies. Eventually, she and her team of scientists hope to develop a technology for replacing the faulty tumour suppressor gene with a normal copy: “Our goal is to repair the damage to the DNA and thus restore the tumour suppressor genes’ ability to function as a gatekeeper against cancer,” she says.