The Lunenfeld: 2009 Research Breakthroughs

Dr. Jeff Wrana pioneered the DyNeMo technique to help scientists assess patients’ prognosis in breast cancer and help determine optimal treatment. In a study published by Nature Biotechnology in February, Dr. Wrana and his team unveiled the tool, and explained that it can predict with more than 80% accuracy a patient’s chance of recovering from breast cancer.

 

Understanding how nerves migrate to the proper places during development has been a life-long obsession of Dr. Joe Culotti.  In February, he published a landmark study in the journal Nature Neuroscience that revealed how opposing chemical signals help define the appropriate positioning of neurons and their axons (the cells of our nervous system, with their branch-like endings), with respect to other neurons and supporting cells. In a second paper in Nature Neuroscience, Dr. Jim Woodgett’s group, in collaboration with Dr. Bill Snider at the University of North Carolina, revealed a ‘master-switch’ protein that defines the numbers of neuronal cells that will ultimately form in the brain. This finding may help in replacing damaged brain cells lost through brain injury or neurodegenerative diseases such as Alzheimer's.

 

Also in February, Dr. Daniel Durocher and his team discovered that a gene known as RNF168 is mutated in the RIDDLE syndrome, a rare and genetic immunodeficiency disorder characterized by developmental abnormalities and sensitivity to radiation. The findings were published in Cell, and are expected to help improve diagnose and treatment of the disease. Dr. Durocher’s earlier work revealed that a gene known as RNF8 helps guide BRCA1, a protein that repairs DNA damage known to cause breast cancer. By guiding BRCA1 to the damaged DNA, RNF8 helps ensure that the necessary repairs can be made.   

 

In a study released in March, Dr. Andras Nagy reported a new method of creating stem cells that could lead to possible cures for devastating diseases including spinal cord injury, macular degeneration, diabetes and Parkinson’s disease. The study, published in Nature, accelerates stem cell technology and provides a road map for new clinical approaches to regenerative medicine. The discovery also put Dr. Nagy on Scientific American’s Top 10 Honour Roll for the year, and generated significant media interest in Toronto (including a December 22 “top 2009 breakthroughs” news report on CBC’s The National news).

 

In a study published by the New England Journal of Medicine in June, Dr. Katherine Siminovitch discovered a new genetic pathway (a gene ‘road map’) that could provide personalized treatment options for patients with a devastating liver disease. The study offers great hope in treating other autoimmune diseases such as rheumatoid arthritis.

 

The summer months were busy for Dr. John Roder andhis team inthe neurobiologylab.In August,Dr. Roder published a study offering new evidence that a faulty version of a gene known as Atp1a3 is linked to epileptic seizures in mice. Then in September, Dr. Roder and other researchers discovered a molecular link between intelligence and curiosity, which may lead to the development of drugs to improve learning. In a September issue of the journal Neuron, the researchers reported the interaction of two proteins in a small region of the brain called the dentate gyrus, which plays an important role in long-term memory and spatial navigation. They found a molecular link that holds promise for future cognitive therapies.

 

Dr. Frank Sicheri and researchers at the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal discovered a new way to block a gene implicated in cancer, which may lead to the development of more effective cancer therapies. The findings, published in a September issue of Nature, shed new light on the activation mechanism of the RAF protein kinase which, when mutated, is responsible for more than 25% of cancers. Understanding this mechanism may lead to novel anti-cancer agents designed to minimize the toxic side effects caused by chemotherapy.

 

Also in September, Dr. Sabine Cordes and other researchers made a breakthrough in understanding how gene activity is coordinated at a global level. The researchers were looking at the function and location of Polycomb Response Elements (PREs), which are short regions of DNA that switch genes on or off. Scientists previously thought that PREs existed only in fruit flies; Dr. Cordes’ discovery is the first time these polycomb control elements have been confirmed in mammals. The finding may lead to new insights into diseases such as schizophrenia and cancer, and provides further evidence that studying fundamental processes in simple organisms like fruit flies can lead to important information about human diseases.

 

It was an exciting year for Dr. Bob Casper and his team at the Lunenfeld. In October, collaboration between his lab and Dr. Aaron Wheeler’s team at the University of Toronto resulted in an innovative approach for measuring estrogen levels in clinical samples. The ‘Lab on a Chip’ approach employs silicon wafer-based electronics technology to extract estrogen from as little as 1 microliter of sample (1000x less material than typically required), and could lead to more sensitive diagnostic tests to assess the risk of breast cancer. And earlier in the year, Dr. Casper and his team made a discovery that could improve the health of night shift workers. Since most of the adverse health affects of exposure to light at night are caused by a narrow range of wavelengths in the blue zone of our visual spectrum, Dr. Casper and his team developed special lenses that filter out these particular wavelengths. Wearing the lenses suppressed hormone disruptions and improved alertness, performance and mood during simulated shift work.

 

In an international collaborative study, investigators including Dr. Mark Silverberg discovered five new regions in the genome associated with susceptibility to inflammatory bowel diseases (IBD) in children and adolescents. This is a major step toward understanding the causes of these diseases and the development of advanced drug therapies. The study, published in Nature Genetics in November, is the first genome-wide association study performed exclusively in early-onset IBD and the largest pediatric study of its kind.

 

In December, Kyoto Prize Laureate Dr. Tony Pawson discovered a new technique that allows scientists to monitor communication between cells for the first time. The method is likely to make laboratory studies of cancers and other human diseases, and assessment of new drugs to target them, more accurate. Research conducted earlier this year by Dr. Pawson has also revolutionized scientists’ understanding of how cells function. He and colleague Dr. Gary Bader looked at levels of an amino acid called tyrosine, in the cells of several species. Tyrosine is a target of enzymes called tyrosine kinases that regulate proteins. These kinases play a key role in instructing cells to move, grow and die; but they can also become damaged and send the wrong signals, leading to cancer and other diseases. Their investigations showed that the cells of more complex animals (including humans) have reduced the amount of tyrosine they allow in their proteins, hence limiting the opportunity for kinases to malfunction and thus for cancer to develop.