Decades of discovery

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In 1985, investigators at the Samuel Lunenfeld Research Institute at Mount Sinai Hospital painstakingly examined each gene one by one, searching for anomalies.

Today, robots scan thousands of genes simultaneously, dramatically speeding up the pace of research and shortening the distance from laboratory bench to patient bedside.

In the future, scientists may be able to decode individual differences in mutated genes that vary from person to person and tailor treatments to a patient’s genetic make-up to better target disease.

The institute’s groundbreaking scientific discovery and future vision merged this year during Decades of Discovery, the 20th anniversary of the Samuel Lunenfeld Research Institute (SLRI), where scientists celebrated how the translation of past research has impacted on patient care – and will continue to do so at an increasing rate.

Over the past two decades, research at the SLRI – home to 31 investigators and more than 500 staff – has been building cumulatively according to Dr. Stephen Lye, Associate Director of the Institute.

“The Institute is a generator of new knowledge, a new understanding about disease and ailments,” said Dr. Lye. “We take that knowledge and use it over different time scales to positively impact the health of our patients. We’re a hospital-based institute so our goal is to have our research impact on patients not just in our hospital, but everywhere.”

Research has been translating into better practices in patient care throughout the Institute’s history but is now “exponentially increasing,” said Dr. Lye, adding that basic fundamental research – the generator – will eventually lead to clinical treatments and cures.

Take Dr. Tony Pawson’s pioneering work investigating how cells communicate with each other. By understanding the “normal” cell signaling mechanisms and how abnormal signaling leads to disease, researchers can design new drug therapies that specifically intervene to inactivate or repair the faulty signal. This type of research has led the way to the development of drugs like Gleevac, a key cancer drug in use today.

Dr. Frank Sicheri, part of a younger generation of researchers, takes this fundamental research, and conducts further research on the structure of proteins.

Without their fundamental cellular research, “we wouldn’t be at the cutting edge that we are at now,” said Dr. Sicheri. “We all have different niches, but they’re all parts of the same puzzle. We’re not fully independent – we share resources, we have collaborations. It works.”

Dr. Sicheri’s work in how proteins regulate biological processes represents a closer step in translating research to patient treatment, he said. After breaking down a structural mechanism, he helps drug companies develop drugs that will complement the error in the genetic code. The goal of drugs, if successfully developed, will ultimately treat cancer.

This year, one of the SLRI’s most noted research breakthroughs was Dr. Andras Nagy’s development of Canada’s first two human embryonic stem cell lines. These will be freely available to the Canadian scientific community, enabling scientists to discover potential treatments for a variety of diseases.

“We should push more and more energy toward that basic research which could ultimately lead to clinical applications for diseases such as cancer, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, diabetes and spinal cord injuries,” said Nagy.

Dr. Lye explains that by comprehending the fundamentals, further research can be conducted on a more complex, human level.

“The goal now is to try and understand the small genetic differences between each of us that contribute to ill health and then use this information to personalize therapies to individuals,” he said. “Why is it that in two patients with the same cancer, in one it develops aggressively, and in the other, slowly? What makes one patient respond to drug A, when another patient does not respond at all?”

Dr. Lye and his team have identified genes that contribute to the onset of labour, advancing knowledge of the mechanisms that lead to pre-term labour – the leading cause of death and disability in newborn infants. Based on laboratory research, Dr. Lye is leading researchers testing the efficacy of a new therapy to prevent pre-term labour.

Dr. Steven Gallinger’s lab recently published the largest North American study describing the contribution of the MYH gene to colorectal cancer risk. The lab analyzed DNA samples and family history questionnaires from more than 2,000 Ontarians and identified subjects who have mutations in this newly identified gene, which is one of the hottest topics in colorectal research.

Dr. Gallinger’s team continues to define genetic analyses that differentiate colon cancer patients who will benefit from chemotherapy and those who will not.

Dr. Katherine Siminovitch has identified mutations in several genes that control immune function. Dr. Siminovitch, daughter of the SLRI’s founding director, Dr. Lou Siminovitch, has shown that a mutation in the SHP1 gene leads to systemic autoimmunity, a finding that has major implications for this serious and widespread condition.

Most recently, Dr. Siminovitch identified a gene that increases an individual’s susceptibility for Inflammatory Bowel Disease. Further research is being conducted to understand why patients with a predisposition to disease respond differently to drug therapies.

Dr. Pawson said that over the last 20 years, the SLRI’s success has been based on many of these excellent scientific discoveries, which he credited at this year’s anniversary celebrations to a tradition of excellence in scientific training. “It has been a time to celebrate our accomplishments and look forward to the promise the future holds for research,” he said.

To launch the next 20 years of groundbreaking research, the SLRI has also recently appointed a new director, Dr. Jim Woodgett, replacing Dr. Pawson who chose to step down recently to focus exclusively on his research.

The future is bright at the SLRI, which will continue to focus strategically on educating the new wave of scientists.

“It’s remarkable how much the Lunenfeld has contributed to the world,” Dr. Alan Bernstein, former director of the SLRI and current president of the Canada Institutes of Health Research said at the Decades of Discovery celebration at Mount Sinai Hospital.

“The legacy of the Lunenfeld is not just the science that has come out of here but the quality of the trainees who have emerged from here and gone on to do great things.”

And with advancements and new tools, researchers are able to continue to move forward and accomplish scientific goals only dreamed of 20 years ago, said Dr. Lye.

Construction is underway on two innovative projects: the Toronto Centre for Phenogenomics – a four-hospital initiative, and an expansion of the Centre for Systems Biology and Translational Research at the SLRI. In these two centres of excellence, to be opened in 2007, basic research will continue to be developed and translated into improved patient care.

“We’re at a point where we are increasingly benefiting from the basic research we’ve been doing,” said Dr. Lye. “We are realizing the investment of all of the tremendous research we have been working on in the Samuel Lunenfeld Research Institute for the past 20 years. This is a major milestone and we will continue to accomplish great things.”