Best Medicine Matters

SPRING 2010

The Best Medicine Matters

5 2 5 d l e f n e Lun

Today’s Science. Tomorrow’s Medicine.

Celebrating 25 Years of Research, including Eureka Moments, Stories Behind the Science, Donors Inspired by Discoveries

A PUBLICATION OF THE MOUNT SINAI HOSPITAL FOUNDATION

The Lunenfeld: Then and Now “The story’s very simple,” says Dr. Louis Siminovitch. “Irving Gerstein, chair of the Hospital board, asked me what it would take to create a first-class research facility.

I told him, ‘50,000 square feet and $2 million for the first year’s budget.’”

It was the early 1980s, and research was beginning to have an impact on patient care. Gerstein and the Hospital’s Executive Director, Gerald Turner, were determined Mount Sinai would play a pivotal role in this burgeoning field.

They asked Dr. Siminovitch — creator of the Department of Medical Genetics at the University of Toronto and SickKids’ Geneticist-in-Chief — to help Mount Sinai expand its scientific capability.

Along with advising on the facilities, Dr. Siminovitch participated in the search for the institute’s first research director — a position he was eventually talked into taking. “I was going to be 65 when the institute opened, and I said, ‘Don’t you want somebody younger?’ But they said, ‘We want you.’”

Recruiting for a new institute was challenging, but Dr. Siminovitch saw it as an opportunity. “I was not going to just hire scientists,” he recalls. “I was going to hire leaders and they would build their teams.”

Dr. Siminovitch also established the institute’s priority areas: cancer and cell biology, molecular and developmental

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Dr. Lou Siminovitch, Director of the Lunenfeld from 1985 to 1995

Dr. Jim Woodgett, Director of the Lunenfeld since 2005

biology, immunology and neurobiology, epidemiology and perinatology.

“We started off like a ball of fire because we had recruited excellent people with excellent programs,” he says.

“ The Lunenfeld is small and efficient and significantly outpunches its weight.”

D r . J im W oodgett

“Through research we find new knowledge, understanding and therapies that will ultimately improve outcomes and quality of life for patients here at Mount Sinai, and around the world,” he says.

“The Lunenfeld is small and efficient and significantly outpunches its weight,” he explains. “Our scientists consistently publish more high-impact papers than far larger institutions, including many universities! I think this is largely due to our focus on depth rather than breadth. What our 35 researchers do, they do brilliantly.”

“I’d say that’s as true today as it was when the Lunenfeld began,” says Dr. Jim Woodgett, Research Director since 2005.

“This institute made a name for itself remarkably quickly; it was named one of the world’s top 10 biomedical research centres before its 20th anniversary.”

Dr. Woodgett and Dr. Siminovitch are also proud of the invaluable donor support that built and nourishes the Lunenfeld.

The generous contribution of Samuel Lunenfeld, a lifelong supporter of research, is reflected in the Institute’s name.

Like Dr. Siminovitch, and the other directors who have guided the institute, Drs. Alan Bernstein and Tony Pawson, Jim Woodgett is passionate about scientific research.

“I like to tell people that it is our donors who provide the springs that enable us to jump higher,” says Dr. Woodgett.

“After 25 years, Lou’s vision has been realized in spades.”

25 Years of Eureka Moments

Since 1985, scientists at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital have pushed the boundaries of discovery, bringing new insights to The Best Medicine. Read on for a snapshot of research breakthroughs.

1986: Dr. Tony Pawson, Apotex Chair in Molecular Oncology, discovered how cells communicate with each other. His

continued groundbreaking work in cell signaling is likely to make laboratory studies of cancers and other human diseases, and assessment of new drugs to target them, more accurate.

1988: By studying the nematode worm C. elegans, Dr. Joe Culotti and his team were the first to identify specific nerve guidance molecules that help form the basic framework of the nervous system.

1989: Dr. Katherine Siminovitch, Sherman Family Research Chair in Genomic Medicine, discovered a genetic marker for Wiskott-Aldrich syndrome, prompting genetic counsellors from across north America to contact Mount Sinai for help in prenatal diagnosis of this fatal condition.

1991: Through research on sugar molecules on the surface of cancer cells, Dr. Jim Dennis found that a combination of swainsonine (a chemotherapy drug) and interferon could help block the growth of solid tumours.

1996: Dr. Alexander Logan’s team showed that, contrary to popular belief, salt does not increase blood pressure in healthy people, a discovery that made headlines around the world.

1998: Drs. Isabella Caniggia and Stephen Lye, Mount Sinai Hospital Auxiliary Chair in Women’s and Infants’ Health Research, discovered that a biochemical factor called TGFb 3 remains elevated in pre-eclamptic pregnancies, enabling early diagnosis of the condition.

Continued on page 7

Welcome to our 25th anniversary celebration of the Samuel Lunenfeld Research Institute!

I am a huge fan of research. I admit that I’m a little awed by our scientists’ incredible depth of knowledge and imagination. Our Lunenfeld investigators add another vital ingredient to this mix: compassion. Thanks to collaborations with Mount Sinai Hospital clinicians, our researchers are attuned to more than the science of a disease; they understand its impact on people. Because of this, the Lunenfeld is renowned for rapidly translating laboratory discoveries into new therapeutic and diagnostic tools.

Featured here are stories about some of these successes. The discoveries cover diverse areas of science, but they share a common thread: philanthropy. Lunenfeld scientists enjoy a high degree of success in gaining grants from research agencies, but donor support of the Institute’s operating costs provides the essential backbone of the Lunenfeld.

Your contributions are so valuable to the Lunenfeld and, thus, to patients and their families in Canada and beyond. Thank you for your support.

With warm regards,

Susan Horvath President, Mount Sinai Hospital Foundation 3

Research Tour Inspires Donor

Ridham Desai and Denise Altschul

There’s nothing quite like exploring a laboratory where great discoveries are being made to bring home the power and excitement of medical research.

and the potential of the discovery to transform treatment for spinal cord injury, Parkinson’s disease, diabetes and other devastating conditions.

Ms. Denise Altschul — a grateful patient and dedicated monthly donor — recently joined PhD candidate Ridham Desai for a tour of his workplace, Principal Investigator Dr. Andras nagy’s lab. The experience moved her deeply.

“This tour motivated me to leave a gift in my will to Mount Sinai and encourage others to consider doing the same,” says Ms. Altschul. “Large or small, a gift in a will can have an enormous impact on the future of medical research at the Lunenfeld, so that this great work is continued for the benefit of generations to come.”

Ridham explained some of the steps leading to Dr. nagy’s groundbreaking development of a new method of creating stem cells from adult skin cells,

Did you know?

Donate to research, and you’ll be giving much more than you realize.

That’s because one donor dollar = eight dollars for the Lunenfeld, thanks to competitive grants and external funding.

Send a heartfelt message with our Tribute Cards!

Express yourself with our Mother’s Day, Wedding and Celebration cards. See the full range of Tribute cards at mshfoundation.ca Order online or call 416-586-8203 ext. 3936.

The Stories Behind the Science All the scientists at the Samuel Lunenfeld Research Institute share a passion and dedication for their research. Some are driven by their inherent curiosity and zeal for pure science; others are motivated by a deeper personal investment.

Dr. John Roder A Senior Investigator at the Lunenfeld and Professor in the Department of Molecular Genetics at the University of Toronto, Dr. Roder holds a Canada Research Chair in Learning and Memory.

His research focuses on the roles of molecules in the central nervous system and aims to determine targeted new drug therapies for neurological and psychiatric diseases including depression, anxiety, obsessive compulsive disorder and schizophrenia.

But it wasn’t always so. In fact, Dr. Roder began his scientific career as an internationally renowned cancer researcher. When his son nathan was diagnosed with schizophrenia at age 18, Dr. Roder turned his considerable talent to study this complex brain disorder.

Dr. Isabella Caniggia Dr. Caniggia, Principal Investigator at the Lunenfeld and a leading authority on placental development, knows firsthand the potentially devastating effects that pre-eclampsia (the most common pregnancy-related complication) can have. Her younger sister Alessandra was born with cerebral palsy and requires a wheelchair because of this enigmatic disease.

“I started out as a paediatrician with hopes to make a difference in this area,” said Dr. Caniggia. “But I was always attracted to basic science and the opportunity it presented to get at the roots of pre-eclampsia. It makes me very proud now to see the tangible aspects of my research.”

Pre-eclampsia affects five to seven per cent of all pregnancies, and is a leading cause of mother and fetal deaths.

Dr. Caniggia and her team have made exciting progress in identifying genetic alterations, or biomarkers, that predict whether pregnant women will have early- or late-onset pre-eclampsia.

Recently, Dr. Caniggia licensed her biomarker findings to help develop a diagnostic tool that will detect and manage pre-eclampsia in expectant mothers.

“Because of my son, it became so important for me to change my area of focus,” said Dr. Roder.

In a pivotal study in 2007, Dr. Roder demonstrated for the first time in mouse models that malfunction of the gene DISC 1, previously associated with schizophrenia and depression, causes symptoms of those disorders. The discovery could change the way that scientists diagnose schizophrenia and may open the door to new treatments.

“I’m optimistic about some of the new advances in therapy for schizophrenia,” said Dr. Roder. His son, a promising student and violinist, is now 26 years old.

Continued on page 8

Curious about research?

Serious about science?

Meet the scientists from the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, learn about their research and their amazing discoveries. It’s research revealed, at mshfoundation.ca

The Quarter-Century Club “We owe it all to Lou,” says Dr. John Roder, Senior Investigator at the Samuel Lunenfeld Research Institute. He is referring to Dr. Lou Siminovitch, the Institute’s first director and the man who recruited him in 1985.

Dr. Marc Grynpas

Dr. Roder is an “Original” — one of a number of scientists who have been with the Lunenfeld from its first years. This longevity is considered a phenomenon in the competitive, fast-paced world of scientific research.

“I’ve been pursued by other institutes, but I’ve stayed because this is truly the best place in Canada to do research, and one of the best in the world,” Dr. Roder explained.

Dr. Irene Andrulis says that, “I can’t talk about my 25 years at the Lunenfeld without talking about Mount Sinai Hospital. My clinical colleagues have added so much value to my career — they have made my research work.

“I hope that I have served as a conduit between basic science and clinical care,” she says, referencing the adoption of screening for the HER2 gene as an example. Dr. Andrulis and her colleagues proved that increased copies of this gene are a predictor of recurrence of breast cancer, and then worked with physicians and ministries to make sure this test was adopted in clinical settings.

Dr. James Dennis shares this enthusiasm. “It is so much better to work in a hospital,” he says. “It gives our work context, meaning and urgency.” He has collaborated with Mount Sinai’s Dr. Carol Swallow, a surgical oncologist, for nearly a decade, looking for ways to understand and prevent the spread of cancer.

Asked about the Lunenfeld’s greatest contribution to medical science, Dr. Dennis answers unequivocally: “our students. We have trained countless scientists who have gone out into the world to do great things; we have built a legacy of scientific stars.”

Dr. Marc Grynpas, a Belgian by birth, agrees. He’s trained researchers from Iran, China, Brazil, Belgium, Germany and Korea. “It’s a pretty solid marker of success when a relatively small organization like ours has no trouble attracting the world’s brightest young talent.”

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Dr. James Dennis

Dr. Irene Andrulis

“ This is truly the best place in Canada to do research, and one of the best in the world.”

D r . J oh n R oder Attracting the best is a legacy bestowed by Dr. Siminovitch, says Dr. S. Lee Adamson, Anne Tanenbaum Chair in Molecular and Developmental Biology, Senior Investigator and Director of the Lunenfeld’s Research Centre for Women’s and Infants’ Health.

“From the earliest days, we’ve had the best people pursuing integrative and collaborative projects with each other and with the Hospital. We really get at the heart of the problems and the challenges patients face,” she explains.

Dr. Tony Pawson, Apotex Chair in Molecular Oncology, and the Lunenfeld’s Distinguished Investigator, says of the institute, “The ethos has remained the same. We recruit outstanding young scientists who continue to infuse the place with fresh, innovative ideas, and we collaborate to make sure we’re doing the best work.”

25 Years of Eureka Moments From page 3 1998: Drs. Irene Andrulis and Shelley Bull established that a genetic test could identify women with nodenegative breast cancer (cancer that has not metastasized to the lymph nodes) who are at increased risk of disease recurrence.

1999: Dr. Bernard Zinman, Sam and Judy Pencer and Family Chair in Diabetes Research, discovered that diabetic First Nation adults have a high frequency of a mutation in the HNF1 gene.

2004: Dr. Steve Gallinger, Oakdale Golf & Country Club/George Knudson Research Chair in Gastrointestinal Cancer, identified a genetic variation associated with colorectal cancer — the first such genetic predictor and a tool for future screening methods.

2005: Canada’s first two human embryonic stem cell lines were developed by Dr. Andras Nagy. He has since discovered a new method of creating stem cells that could lead to possible cures for spinal cord injury, macular degeneration, diabetes and Parkinson’s disease.

2007: A ‘genetic roadblock’ was discovered by Dr. Jim Woodgett that may result in new treatments for Type 2 diabetes.

Dr. John Roder demonstrated for the first time that malfunction of the gene DISC 1, previously associated with schizophrenia and depression, causes symptoms of those disorders.

Dr. Julia Knight discovered that increased vitamin D levels during adolescence may reduce risk of breast cancer later in life by over 30 per cent.

2008: Dr. Frank Sicheri found that a protein called IRE1 provides two opportunities for the development of drugs to treat diseases including cancer.

A new once-weekly treatment for type 2 diabetes was reported by Dr. Daniel Drucker, a regimen that could replace the more common twice-daily injection.

Dr. Pamela Goodwin, Marvelle Koffler Chair in Breast Research, uncovered a link between vitamin D deficiency and poor prognosis of breast cancer.

Dr. Rayjean Hung found that chromosome 15 is associated with lung cancer, a finding that provided new clues on how smoking tobacco can cause this cancer.

2009: The DyNeMo technique was pioneered by Dr. Jeff Wrana, Mary Janigan Research Chair in Molecular Cancer Therapeutics, to help assess patients’ prognosis in breast cancer and help determine optimal treatment.

Dr. Dan Durocher, Thomas Kierans Research Chair in Mechanisms of Cancer Development, discovered that the gene RNF168 is mutated in the RIDDLE syndrome, a rare genetic immunodeficiency disorder, enabling better diagnosis.

Dr. Sabine Cordes and her team were the first to identify short regions of DNA that switch genes on or off in mammals. The finding may lead to

new insights into diseases such as schizophrenia and cancer.

Dr. Bob Casper, Camille Dan Family Research Chair in Translational Cell Biology, and his team developed special lenses to protect night shift workers from reduced melatonin levels, to lower their risk of cancer and other diseases.

Investigators including Dr. Mark Silverberg, Gale and Graham Wright Research Chair in Digestive Diseases, discovered five new regions in the genome associated with susceptibility to inflammatory bowel diseases in children and adolescents, a finding that may lead to new therapies.

To read about more eureka moments, please go to mshfoundation.ca

Upcoming Events For details, please see the Calendar of Events at mshfoundation.ca or call 416-586-8203.

May 1 Shayam Kaushal Gala Dinner; $125 per person May 25 The Mount Sinai Hospital Auxiliary Gala; from $750 per person June 17 Corrado Family Golf Tournament June 21 Mount Sinai Hospital Classic Golf Tournament; $3,000 per foursome July 24 Shawn Michael Gourlie Charity Golf Tournament August 13 Samantha Flannigan Memorial Golf Tournament September 26 Scotiabank Toronto Waterfront Marathon; from $35 per person

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The Stories Behind the Science Meghan Sauvé A Master of Science graduate from Dr. Daniel Drucker’s lab, Meghan Sauvé has a vested interest in diabetes research. Her father Carl was diagnosed with Type 1 diabetes 40 years ago, and has since developed severe eye and kidney problems related to the disease.

“Ever since I was a little girl, I’ve wanted to help cure diabetes,” said Meghan. “It’s such a motivating feeling to know that what I’m doing is making a difference.”

Discoveries in Dr. Drucker’s lab have already contributed to the development of two new treatments for Type 2

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diabetes. Currently his research team is focused on a family of hormones produced in the pancreas, gastrointestinal tract and brain that control blood glucose and insulin secretion. Meghan and other researchers in Dr. Drucker’s lab are working to create compounds that mimic the effects of these hormones, with the goal to develop new and improved therapies for diabetes.

Meghan’s father, now age 67, has greatly benefited from advances in diabetes treatments, combined with a steadfast commitment to lifestyle changes to manage his condition.

Meghan Sauvé

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