Biomedical Powerhouse How the Samuel Lunenfeld

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By Karin Fleming

Starting and maintaining a successful biomedical research institute is just like science itself: an experiment. Some work, some don’t, and much of it is calculated guesswork with skillful adjustments along the way. The unpredictability of research and its vulnerability to economic and industry-related trends, as well as fierce competition for funding from government or donors can undermine the best laid plans.
The Samuel Lunenfeld Research Institute of Mount Sinai Hospital — celebrating its 25th anniversary this year — is regarded as one of the world’s top 10 centres in biomedical science, and one of Ontario’s primary centres for genetics research and molecular medicine.

As a testament to the Lunenfeld’s success, when compared with peer universities or research centres:
•     Lunenfeld researchers consistently attract competitive research funds at rates above (and often double) the national average;
•     In 2009, Lunenfeld investigators authored over one quarter of the primary research papers in the top 30 biomedical journals published by all Toronto health scientists — even though Lunenfeld researchers represent under five per cent of the total number of biomedical researchers in the city;
•     Almost 90 per cent of the Lunenfeld’s funding is derived from competitive research granting agencies, and;
•     Lunenfeld scientists currently hold more than $200 million in grants and awards.

The Lunenfeld was a model for other successful Canadian research centres including the Institute for Research in Immunology and Cancer (IRIC) in Montréal, as well as the Terrence Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto.
So what makes good science great, how do research institutes succeed, and what are the challenges and
opportunities facing biomedical research centres in Canada? How does the Lunenfeld, a small research centre compared with its peer institutions, consistently lead efforts in biomedical research?
To explore these questions, we talked with past and present directors of the Lunenfeld, as well as directors of other leading biomedical research institutes in Canada.

Early days at the Lunenfeld
“I had a very simple plan,” says Dr. Lou Siminovitch, the Lunenfeld’s inaugural director. “I was not going to just hire scientists; I was going to hire leaders. We started out like a ball of fire—with good people, first-rate research and excellent programs.”

It was 1985, and Dr. Siminovitch’s strategy upon beginning his nine-year directorship of the Mount Sinai Hospital Research Institute would lead his team of talented young scientists to become a virtual phenom in the global biomedical community. Dr. Siminovitch, who had developed research teams at the Ontario Cancer Institute and The Hospital for Sick Children, began his role as director by recruiting 30 internationally renowned investigators divided among five multidisciplinary teams.

According to Joseph Mapa, president and CEO of Mount Sinai Hospital, “The rationale for a research institute within the Hospital was the pursuit of excellence, and the philosophy that its presence would improve and enhance patient care in terms of knowledge transfer, and the caliber of clinicians and scientists attracted to our hospital.”

In a quantitative sense, after only three years the Institute’s scientists had already published 150 papers in leading peer-reviewed biomedical journals and obtained over $10 million in operating and salary awards from external agencies, reflecting the quality and impact of these investigators on the world’s scientific stage.

Critical support from donors
In 1989, the Samuel Lunenfeld Foundation donated $7.5 million to the Institute. At that time, it was one of the largest gifts to medical research in Canadian history. In recognition of this gift, the Mount Sinai Hospital Research Institute was renamed the Samuel Lunenfeld Research Institute of Mount Sinai Hospital.

After Lunenfeld’s passing, his family carried on a tradition of giving in support of research at Mount Sinai. Since the Lunenfeld’s inception, the Mount Sinai Hospital Foundation has contributed approximately $175 million in support of Lunenfeld research. “This ongoing support is essential in providing stability to the Institute and enables efficient infrastructure as well as matching funds for external awards,” says Dr. Jim Woodgett, the Lunenfeld’s current director.

New leadership, continued success
In 1994, the directorship transferred to Dr. Alan Bernstein, one of the Institute’s original scientists, who was committed to furthering the Lunenfeld’s internationally renowned excellence in fundamental science, while strengthening its interactions and collaborations with the hospital.

“At that time, the science at the Lunenfeld really took off and our investigators blossomed,” says Dr. Bernstein, who later became the inaugural president of the newly created Canadian Institutes of Health Research and is now executive director of Global HIV Vaccine Enterprise in New York.
In preparing for the 21st century and its accelerating pace of discovery, new projects were initiated in 1998 in the Lunenfeld’s Proteomics and Bioinformatics division, the Centre for Modeling Human Disease, and the Fred A. Litwin Centre for Cancer Genetics. “These initiatives have proven to be a model for other research institutes and a key factor in enhancing the Lunenfeld’s pre-eminence in biomedical research on a global scale,” says Dr. Bernstein.
And consistent with early traditions at the Lunenfeld, the new teams were encouraged to intersect with the clinical interests of Mount Sinai Hospital.

“The Lunenfeld is well poised to make a big impact because of the combination of detailed clinical information and sophisticated science,” says senior investigator Dr. Lee Adamson, who was recruited in 1986 to join the Lunenfeld’s Perinatology Division. (The Lunenfeld is now comprised of 34 Principal Investigators, nine of whom are MDs and practising physicians.)

The Lunenfeld also benefited from the opening of the Research Training Centre in 1998, a program that offers trainees (drawn to the Lunenfeld from countries as far ranging as Iran, China, Belgium, Korea and more) an exceptional research-based learning environment.

“Perhaps our biggest contribution to biomedical research in Canada is the network of trainees from our centre who act as ambassadors for the Lunenfeld,” says senior investigator Dr. Jim Dennis, whose lab recruits several new trainees each year.
Dr. Tony Pawson, distinguished investigator and Apotex chair in Molecular Oncology, took up the directorship in 2000, keeping the Lunenfeld at the forefront of scientific advances.

“From the beginning, the ethos of the Institute has remained the same. We recruit outstanding young scientists, promote tremendous collaboration and nurture new ideas,” says Dr. Pawson. “It’s extremely rewarding and stimulating to think of what has been done, and what will be done.”
That year, the federal and provincial governments awarded Lunenfeld researchers a combined $20 million through innovation competitions, which allowed for the establishment of exciting new programs of scientific research including the Centre for Genomic Medicine and the Prosserman Centre for Health Research.

These centres enabled the Lunenfeld to participate in worldwide endeavours to map the human genome and better understand gene and protein function, with the goal to enhance the diagnosis and treatment of diseases including cancer, diabetes, immune and nervous system disorders, as well as developmental disorders.

New funding also helped the Lunenfeld leverage increasingly advanced techniques to study the genetics of human diseases and analyze gene and protein function, using some of the world’s most sophisticated instruments for mass spectrometry, robotics and informatics, imaging, computational approaches, proteomics, X-ray crystallography, DNA microarrays and more.

For example, the Lunenfeld’s leading-edge robotics facility, pioneered by Dr. Jeff Wrana (senior investigator and the Mary Janigan Research chair in Molecular Cancer Therapeutics) enables researchers at Mount Sinai Hospital and among Ontario’s biomedical community to analyze the function of thousands of genes at a time, and rapidly identify the properties and processes important in human disease.

“When I first started working in research, scientists were arguing about whether genes were made of proteins or DNA; now, we’re conducting genome-wide sequencing,” says Dr. John Roder, Lunenfeld senior investigator and a world-renowned neuroscientist.

A model for other biomedical institutes
in Canada
Along with the Lunenfeld, other Canadian research centres including IRIC in Montréal and the Terrence Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto have grown and flourished in a climate that fosters preeminent biomedical research.

Dr. Guy Sauvageau, IRIC’s chief executive officer and Scientific director believes that the spectacular growth in biomedical knowledge and technology in Canada is in large part due to support from government agencies including the Canada Foundation for Innovation (CFI), the Canadian Institutes of Health Research (CIHR) and the Canada Research Chair program.

“In the U.S., for example, this kind of support is not available,” says Dr. Sauvageau. “A massive investment from the CFI, CIHR and others has allowed us to build multiple technology platforms and recruit and retain top-notch scientific talent.”
Established in 2002, IRIC is a fully integrated systems biology research and training centre focused on immunology and cancer, and is home to 25 principal investigators. Determined to offer the best research environment possible to support the work of an elite team of investigators, the Université de Montréal sought the counsel of some of the most respected health research leaders in the international community before establishing IRIC as its research institute.

“We consulted with key players at the Lunenfeld, the Max Planck Institutes in Germany and the Institute for Systems Biology in Seattle,” says Dr. Sauvageau. “The Lunenfeld had and still has a history of scientific excellence and definitely influenced our early development.

Its team brought the spirit of where biomedical science is going in Canada, specifically to invest in systems biology and leading-edge technology to approach biomedical problems strategically.”
Dr. Sauvageau says this consultation proved invaluable in helping the Université de Montréal refine its vision for IRIC. He also notes that smaller, successful research centres such as the Lunenfeld and IRIC share common features including access to early clinical studies (which assists researchers in translating their discoveries into clinical benefits, a feature made possible through collaboration with clinician–scientists who are practicing MDs), affiliation with a university campus and collaborative multidisciplinary teams.

Dr. Brenda Andrews, a leading Canadian yeast genomics researcher and director of the Donnelly Centre in Toronto, adds that open-concept labs have allowed smaller centres to maximize their collaborative capabilities. “The open-concept aspect of the Lunenfeld’s labs influenced our early development. The Lunenfeld also has an amazing mix of scientists studying various model systems and leveraging innovative technologies. The environment really encourages people to interact.”

In the late 90s, the Faculties of Medicine, Pharmacy, and Applied Science and Engineering at the University of Toronto came together to envision a Centre for Cellular and Biomolecular Research. In 2005, the Terrence Donnelly Centre for Cellular and Biomolecular Research opened its doors to world-renowned researchers from many disciplines focused on identifying the causes and cures of diseases.

“We’ve put together a collaborative team with various areas of expertise focused on biomedical questions and problems. In this way, we’re moving faster and in new directions to help solve some of the most pressing issues in human health and diseases,” says Dr. Andrews. “Smaller research centres can be nimble, adapt to trends and function as a community. You can choose your mission together.”

Collaborations are also important between institutions. For example, the Lunenfeld and the Donnelly Centre will both benefit from the joint affiliation of Dr. Fritz Roth, an acclaimed computational and cellular biologist jointly recruited from Harvard Medical School, by both centres. Dr. Roth was selected as an inaugural Canada Excellence Research Chair (CERC) earlier this year. His role as a CERC is part of a new program initiated by the federal government, to attract the world’s most renowned researchers to universities and institutes across Canada.

The Lunenfeld today, and tomorrow
By 2005, the Lunenfeld was already considered one of the top 10 biomedical research centres worldwide. At the end of that year, the Lunenfeld transitioned to the leadership of Dr. Jim Woodgett, a world-class scientist whose last posting was at the Ontario Cancer Institute of Princess Margaret Hospital.

“I was always impressed by the quality and depth of expertise at the Lunenfeld,” says Dr. Woodgett. “It has always out-punched its weight class and consistently raised the bar in scientific accomplishments.”

The Lunenfeld’s early adoption of new technologies such as RNA interference (RNAi), high- throughput screening, induced pluripotential stem cells, ultra-sensitive proteomics, high resolution live cell imaging, population health analysis and sophisticated mouse models convinced Dr. Woodgett that the Lunenfeld was superbly positioned to leverage its skills in discovery research, into clinical application within Mount Sinai Hospital—especially in the application of genetic knowledge.

“In the past decade, science has revealed how important our individual differences are to propensity for disease or response to therapy,” says Dr. Woodgett. “It feels as though the experience of the past twenty-five years has precisely prepared us for the coming era of personalized medicine. In the next twenty-five years we hope to transform medicine.”