Sinai Health Magazine Spring/Summer 2017

Sinai Health A P U B L I C A T I O N O F S I NA I H EA L T H F O U N DA T I O N

Where the search for connects The Lunenfeld-Tanenbaum Research Institute is leading breakthrough research to bring hope to our patients, present and future

A SU PR TU I NMGN//SW UIM NM T E R 2016 2017

Contents

Sinai Health

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S P R I N G / S U M M E R 2017 Editor-in-Chief Lindsey Hodgson

A window into the future Clinician-scientists at Sinai Health System are studying gestational diabetes, a predictor of future Type 2 diabetes and cardiovascular disease, while helping expectant moms like Victoria manage their health during and after pregnancy

The promise of precision medicine

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Research is driving tailored approaches to treatment for rheumatoid arthritis (RA) and other debilitating autoimmune conditions, offering hope to patients like Erinn, who has been living with RA since age 21

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A connection formed by memory

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Editor Sara Daniels Art Director Cecilia Mok Contributors Eden Biggin Veronika Izabela Bryskiewicz ´ Marcia Kaye John Packman Heidi Singer Annie Tong 3004 Studios

ENVIRONMENTAL ATTRIB

Award-winning brain health researcher Dr. Graham Collingridge is studying how memories are formed — and lost — as he works to develop a new drug that will help patients like Oscar, a retired doctor and Holocaust survivor who suffers from dementia

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“ I want to help save other people. That would be so cool. I think that’s the most amazing thing I can do with the time I have left.”

   

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— JENNIFER LANDA, RIGHT, PATIENT WITH TERMINAL BREAST CANCER

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Health Foundation EXAMPLE 1 : PAPER Sinai 100% RECYCLE ROLL

Targeting gum disease A first-of-its-kind dentistry centre will offer innovative care for patients like Shin who experience chronic, complex oral health conditions, and lead groundbreaking research into how inflammation of the gums affects overall health

Shining a light on breast cancer

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PRODUCTS

M E S SAG E F RO M O U R CO - C H A I RS

In the years to come, doctors will have the tools to customize patients’ treatment to their own genetic makeup or predict how a patient’s unique tumour will behave in order to optimize treatment. These life-changing advances are on the horizon because of innovative research underway at the Lunenfeld-Tanenbaum Research Institute (LTRI) — research that is revealing critical insights into how diseases develop and behave and driving treatment options that were once unimaginable.

For over 30 years, Sinai Health System’s ltri has been connecting the scientific community and patients to discoveries that help to prevent, diagnose and treat some of the most pressing health issues facing Canadians. Throughout this issue of Sinai Health, we celebrate how the power of connections fuels discovery: Researchers connecting with each other, connections made within a research project itself or across fields of study and, most importantly, how these breakthroughs connect back to a healthy society.

David G. Cynamon

These connections directly link to the patients you will read about in this issue. Patients like Jennifer, a vibrant young woman who has faced a terminal cancer diagnosis with courage and hope and the desire to help others. Jennifer is leading her own fundraising campaign and has raised almost $150,000 to support The Jennifer Landa Breast Cancer Visiting Professorship at the Marvelle Koffler Breast Centre, a gift that will bring international breast cancer leaders to Mount Sinai on a regular basis to facilitate the collaboration and sharing of ideas that drive breakthroughs in research and treatment, bringing hope to future patients.

The ltri is a research powerhouse. With some of the best and brightest scientific minds in the world, it has long been an important player in the field of discovery science and has played a critical role in tackling some of the biggest research questions. Its core values of curiosity, creativity and collaboration have persisted throughout its history and have enabled our researchers to make some of the most important connections that have impacted the health of Canadians and beyond.

Howard Sokolowski, O. Ont.

This is why supporting research through philanthropy can be so powerful. Your visionary support can help us make the next vital connection: find a new gene, validate a biomarker, understand how cells behave — connections that are game changers for the health of our patients, present and future.

Dr. Jim Woodgett, Koffler Director of Research at the ltri, explains, “While our results are not always immediate, the investment is measured in years. It’s an investment for the future and a better life for all.”

Your support is where the search for answers connects.

Sincerely,

David G. Cynamon Co-Chair, Board of Directors Sinai Health Foundation

Howard Sokolowski, O. Ont. Co-Chair, Board of Directors Sinai Health Foundation

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SHS News C I R C L E O F CARE AN NO UNCES N EW CEO C A R E Y LUCKI

Carey Lucki has been appointed to the new role of Chief Executive Officer, Circle of Care and Vice-President, Sinai Health System. Previously, Carey served as Interim President and Vice-President of Client Services with Circle of Care. Carey began her career as an occupational therapist and over the past 28 years ART H RI T IS R E S EA R C H has held various operational, administrative policy F O UN DATION J OI NS and programming, project management, quality F O RCES WITH S I NA I and risk and strategic planning roles in both acute H EALT H FOUN DA TION and home/community care settings. As ceo of In December, Arthritis Research Circle of Care, Carey will be the operational Foundation (arf ) entered into leader responsible for delivering timely, efficient an exclusive arrangement with and safe care to over 13,000 clients. In addition, Sinai Health Foundation in order Carey will play a crucial role in accomplishing to advance arthritis and related Sinai Health System’s mission to provide autoimmune disease research. arf exceptional care in hospital, community is now the sole fundraising arm for and home by providing guidance and arthritis and related autoimmune leadership on integration of care in the disease research at Sinai Health System, home and community sector. and the arf team has relocated to the Sinai Health Foundation offices.

Arthritis Research Foundation

To learn how arthritis and autoimmune research is changing the lives of patients, read “The promise of precision medicine” on page 12.

THE CENTRE FOR PH E NO GE NOM IC S AWA R D E D $1 5 M I LLI O N G RA N T

CA REG I V E R F R I E N D L Y H OS P I TA L A N D C O M MUN I T Y HUB AN NO UNCE D

Family caregivers are often not fully integrated into a patient’s care team, which means that their role, expertise and needs may not be acknowledged. With that in mind, and a threeyear, $2.5 million grant from The Change Foundation, Sinai Health System and WoodGreen Community Services have partnered to change the way that hospital care and community services are designed, offered and evaluated. The new Caregiver Friendly Hospital and Community Hub project, which will be based at Bridgepoint Active Healthcare, will partner with family caregivers to build a caregiver-friendly environment that views caregivers as key partners and extends broadly from the hospital and into the community.

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The Centre for Phenogenomics (tcp), a world-class research facility jointly operated by Sinai Health System’s Lunenfeld-Tanenbaum Research Institute and the Peter Gilgan Centre for Research & Learning at The Hospital for Sick Children, has been awarded a grant of $15.41 million over the next five years from the Canada Foundation for Innovation.

The tcp designs and generates mouse models for studying human diseases.

Genetically engineered mice from the tcp are used by scientists from across Canada and around the world to study neurodegeneration, cancer, diabetes and developmental disorders such as autism.

PI LO T PRO GRAM PROV I DES SAF E, AF F O RDABLE PAT I E NT T RANSPO RT S

DR. RU SSE L L GOL D MA N AP P O I N TE D DI R E C T OR OF I NTE R-DE P ART M E N TA L DIV ISIO N O F PA L L IA T I V E C A R E

Sinai Health System is bringing together our palliative care services under the leadership of Dr. Russell Goldman, who will oversee our newly formed InterDepartmental Division of Palliative Care.

Dr. Goldman, who previously served as Director of the Temmy Latner Centre for Palliative Care at Mount Sinai Hospital, will lead our efforts to develop an integrated clinical and academic program in palliative care — the largest in the province. Dr. Goldman will work with stakeholders across the System, including the Temmy Latner Centre for Palliative Care with its large ambulatory and communitybased program and its consultative palliative program at Mount Sinai; Bridgepoint’s 32-bed palliative care unit; and Circle of Care with its community based hospice program. Additionally, Dr. Goldman will partner with University of Toronto leadership in developing and implementing an academic plan for the Division.

Arranging for transportation to various non-emergency appointments during a hospital stay can be challenging for patients and families. But now, inpatients within Bridgepoint’s Orthopedics Unit are benefiting from a new Circle of Care-led initiative that provides safe and convenient transportation to and from their appointments at Mount Sinai and other local clinics.

The pilot program, funded by grants from the Rotary Club of Toronto and the Bill Enkin Foundation, utilizes a wheelchair-accessible van operated by a fully licensed and cpr-trained driver at a reduced cost to the patient and the hospital. Although still in its early days, the goal is to eventually expand the transportation service to other eligible patients at Bridgepoint and Mount Sinai.

DR. CHAI M BE LL NAM E D PHY SI CIAN-I N-CH I E F O F SI NAI H EALT H SY ST E M

Dr. Chaim Bell has been named Physician-inChief and the Sandra and Lionel Waldman Family Chair for the Physician-in-Chief of Sinai Health System. Dr. Bell, who has been Interim Physicianin-Chief since last October, will provide leadership to the Department of Medicine, fostering high quality and innovative research, education and clinical care. Previously, Dr. Bell has played an important role in transformational programs within Sinai Health System, and as a Medical Consultant for the Policy and Innovation Branch in the Ontario Ministry of Health and Long-Term Care. Dr. Bell takes over this important role at a very exciting time for our organization, as our focus on complex patients requires a cross-site medical approach and innovative thinking around optimization of care throughout our system.

Discovery Corner

BR EAK TH RO U GH B L OOD T E S T D E T E C T S PRE ECLAM PSIA I N TH E ABSE NC E OF S Y M P T OMS

Research led by Dr. John Kingdom, a perinatologist at Mount Sinai Hospital and Associate Member of the LunenfeldTanenbaum Research Institute (ltri), has led to a breakthrough blood test for preeclampsia, a rare but deadly complication of pregnancy that is characterized by high blood pressure and can only be fully reversed by delivering the baby. Developed directly from Dr. Kingdom’s research between his ltri lab and Mount Sinai’s Placenta Clinic, the Placenta Growth Factor (p l gf ) test can determine if a woman has preeclampsia in the absence of obvious

Mom Priscilla with her newborn baby

symptoms. Mount Sinai is the first hospital in Canada to offer this test in real time to expectant moms at high risk for developing preeclampsia.

“This newly developed screening test tells us very specifically what a patient’s risk is so we can determine the right level of care,” explains Dr. Kingdom.

“When we can rule out preeclampsia, we’re able to send the patient home instead of admitting her to hospital and we can avoid inducing an early birth unnecessarily. And if there is a real risk, we can act quickly.”

DONOR BREAST MILK REDUCES RISK O F PO T E NTIA LLY FA TA L I LLN ESS I N PRE E M I E S

R EA D A BO U T H OW T H E N E W P R E E C L A M P S IA T E S T HELPED PRISCILLA BECOME A MOTHER AGAIN:

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The Milk Bank is a life-saving resource for preterm babies

Donated breastmilk helps save lives of preterm infants in neonatal intensive care units (nicu s), according to a new study led by Dr. Sharon Unger, Staff Neonatologist and Director of the Rogers Hixon Ontario Human Milk Bank at Mount Sinai, and Dr. Debbie O’Connor, Senior Associate Scientist in Physiology & Experimental Medicine at The Hospital for Sick Children (SickKids). The study showed that using donor breastmilk to supplement mother’s own milk to feed preterm babies in nicus reduces the incidence of a severe and potentially fatal bowel emergency called necrotizing enterocolitis — a common cause of infant mortality in the nicu — from 6.6 per cent to 1.7 per cent. The study was published in the Journal of the American Medical Association.

G E STATIO NA L D IA B E T E S TI E D TO I NC R EA S E D FU TU RE RIS K F OR C ARDI OVAS C U LA R DISEASE

According to a new study led by researchers at Mount Sinai and the Institute for Clinical Evaluative Sciences, women who have had gestational diabetes (diabetes during pregnancy) have an elevated lifetime risk for developing cardiovascular disease, whether or not they develop Type 2 diabetes. While it was previously known that women who had gestational diabetes were at increased risk for developing Type 2 diabetes, this new finding shows that the risk for cardiovascular outcomes such as heart disease and stroke is present in women who had gestational diabetes even if they did not develop Type 2 diabetes. The study looked at data from 1,515,079 women over 10 years, and found that 3 out of 1,000 women with gestational diabetes who did not develop Type 2 diabetes did develop a major cardiovascular outcome, a 29 per cent higher risk than that of women who had neither gestational diabetes nor subsequent Type 2 diabetes. As such, the diagnosis of gestational diabetes can provide an early warning of future risk, and provides a critical opportunity for early intervention. The study was published in Diabetes Care.

MAJO R ST UDY REV EALS GE N ET I C CO N N ECT I O N T O M I CRO BI O M E

Dr. Kenneth Croitoru

A study led by Dr. Kenneth Croitoru, Clinician-Scientist in the Zane Cohen Centre for Digestive Diseases at Mount Sinai and Senior Investigator at the ltri, and collaborator Dr. Andrew Paterson, a researcher at Sickkids, has discovered an association between a unique set of human genes and the makeup of the microbiome, the community of bacteria living in human bodies. The new study reveals that the microbiome is not only impacted by environmental factors, but also by our genes. Among the 1,561 healthy individuals involved in the study, nearly 25 per cent of whom were related, onethird of the bacteria within participants’ microbiomes had a heritability factor. In addition, four specific genes were found to have links to specific bacteria types within participants’ gut microbiomes.

This suggests that our genetics influence what types of bacteria may inhabit our gut, and provides new insights into the relationship between the microbiome and numerous diseases it impacts, such as inflammatory bowel disease (ibd), diabetes and rheumatoid arthritis. The study, published in Nature Genetics, used data from the Genetics, Environmental, Microbial (gem) Project, a major international study Dr. Croitoru is leading to determine the cause of ibd.

N EW ST UDY SHOWS SI GN I F I CANT QUA LITY I M PROV E M E N T I N H I P F RACT URE PATI E N T C A R E

An inter-professional approach to caring for hip fracture patients developed at Mount Sinai has illustrated that a new model in which patient care is co-managed between surgeons and medical staff optimizes care for patients — many of whom are medically complex and frail — and is more efficient and cost-effective for the hospital. According to the new study, led by Dr. Christine Soong, Medical Lead of Sinai Health System’s Urgent and Critical Care Centre of Excellence, this approach has been able to reduce length of stay by 6.3 days, decrease time to surgery by 16 hours, increase the time of initiation of appropriate osteoporosis treatment by 40 per cent and decrease cost per case by almost $5,000. The team involved in the initiative included surgeons, nurses, hospitalists, rehabilitation therapists, anesthesiologists, geriatricians, pharmacists and social workers. In addition, the Mount Sinai team was able to leverage the relationship with Bridgepoint Active Healthcare to streamline the discharge process for the transition team. The study was published in the Journal of Orthopaedic Trauma.

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Where

connects

At its core, medical research is not about cells and synapses, molecules and mouse models. It’s about people — the patients and families whose lives are transformed by disease and improved by treatment, the researchers who dedicate their lives to understanding and treating the illnesses that affect the people we care about. Researchers at the LunenfeldTanenbaum Research Institute at Sinai Health System are doing innovative work every day to help connect our patients — like Victoria, Eva, Erinn, Jennifer, Oscar and Shin, all of whom you’ll meet in this issue — with the best possible care.

WA T C H O U R B E H I N D THE-SCENES VIDEO TO MEET THE PATIENTS AN D RESEARCH E RS IN THIS ISSUE

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WHERE THE SEARCH FOR ANSWERS CONNECTS

Victoria Cho with her daughter Jaime

A window

FUTURE

into the

W R I T T E N B Y: M A R C I A K AY E P H O T O S B Y: J O H N PA C K M A N

Victoria Cho had never heard of gestational diabetes until she was diagnosed with it during her pregnancy. She had certainly heard of diabetes — several members of her and her husband’s families had the disease. But learning that she had a form of diabetes herself came as a shock. “I was quite scared,” recalls Victoria, 33, diagnosed in 2015 when she was six months pregnant with her first child. “I felt it was something very serious that I might not be able to control.”

Victoria was right to be concerned. Gestational diabetes mellitus, or gdm, is a condition that needs to be taken seriously. If untreated, it can have significant effects on women and their babies. But gdm can be controlled. With careful management, most women diagnosed with gdm go on to have safe deliveries and healthy outcomes. Still, those women must be regularly monitored because of their higher lifetime risk of Type 2 diabetes and cardiovascular disease.

increasing obesity and a sedentary lifestyle,” she says, adding that the risk also increases with age. Other risk factors are family history of diabetes and ethnicity, including Asian, Black, Aboriginal, Hispanic and Latin American. But about half the women with gdm have no apparent risk factors at all.

gdm is defined as glucose intolerance that has its first onset and recognition in pregnancy. It happens because a woman’s body can’t make or use enough insulin to respond to the increased demands of pregnancy, due to a chronic defect in her pancreatic beta cells. As a result she develops high blood sugar levels. That’s a problem, since blood sugar, or glucose, passes through to the growing baby. This prompts the baby’s pancreas to secrete extra insulin to move the glucose into the cells to use for energy. This may cause the baby to grow too large — often over nine pounds.

gdm generally disappears completely after women give birth, but the biggest public misconception is that it can all now be forgotten.

“Many people believe that gestational diabetes is just a disorder of pregnancy,” Dr. Feig says. “What they may not understand is it really identifies women who are at greater risk of developing Type 2 diabetes.” Dr. Feig’s team has done research showing that one in five women diagnosed with gdm will develop Type 2 diabetes within nine years, and two in five within 16 years.

Among some non-Caucasian populations the rate rises even higher, to 50 percent. The children of gdm mothers also have a higher risk of developing Type 2 diabetes.

That can lead to complications such as premature birth, injuries from the delivery or the need for a Caesarean section. “There’s also a higher risk that the baby could have low blood sugar at birth and immature lungs,” says noted diabetes researcher and endocrinologist Dr. Denice Feig, Head of the Diabetes in Pregnancy Program at Mount Sinai Hospital, part of Sinai Health System, and an endocrinologist in Mount Sinai’s Leadership Sinai Centre for Diabetes, one of the leading centres for clinical research for diabetes in the world. gdm is on the rise. Dr. Feig led a study showing gdm rates in Ontario women doubled between 1996 and 2010, with one in 10 pregnant women over 30 now affected. “It’s probably due to

A predictor of future health

gdm raises the mother’s long-term risk of high blood pressure, high blood fats and metabolic syndrome. So whether or not she goes on to develop Type 2 diabetes, she will still have a higher-than-average risk of cardiovascular disease. That’s why it’s crucial for women who’ve had gdm to get checked within six months after their pregnancies and on a regular basis thereafter.

Unfortunately, only 20 to 40 per cent of women follow up, likely because most new moms are focused on their infants, not themselves.

“This is one of the great missed opportunities in medicine,” says

WHERE THE SEARCH FOR ANSWERS CONNECTS

Dr. Ravi Retnakaran, who is an endocrinologist and Clinician-Scientist in the Leadership Sinai Centre for Diabetes and Associate Scientist at the LunenfeldTanenbaum Research Institute, the research arm of Sinai Health System. He explains that a diagnosis of gdm offers a valuable preview of what may lie ahead. “It’s telling you something very important about your future risk of a major disease, and it gives us an opportunity to intervene before the development of that condition.”

Managing GDM Victoria was fortunate to be a patient at Mount Sinai. The Centre, by doing and offering research to women like Victoria, keeps up with the latest evidence and technology to improve the care and outcomes of women and their infants. It also works closely with the High Risk Pregnancy Clinic to deliver a multidisciplinary approach to the care of women with gdm. And it has knowledgeable diabetes educators who offer leading-edge classes and individualized counselling.

before her pregnancy she did high-intensity CrossFit workouts, and her job at a jewelry store in a busy Toronto mall kept her on her feet for hours. But with her Asian ancestry and family history of diabetes, she did have gdm risk factors.

of diabetes. “But they also reminded me to continue with what I’m doing or the diabetes could come back.”

Like all women diagnosed with gdm at Mount Sinai, Victoria was encouraged to attend a free class run by a nurse and a dietitian, then go for individual counselling, all at the hospital. From these visits, she learned she needed to make some serious lifestyle changes. Instead of grabbing lunch in the food court or eating dinner when her shift ended at 9 or 10 p.m., she needed to eat three balanced meals and three snacks a day at regular times. She had to limit her favourite carbs — rice and noodles — to one cup per meal. Instead of a bowlful of sweet grapes, she could eat only five. She and her husband, Erle, began reading food labels and cooking more meals at home.

Victoria started taking walks after meals to help her body use up glucose more quickly.

She also learned to prick her finger to regularly test her blood sugar levels to ensure the changes were having an effect.

Dr. Retnakaran’s research team recently found that the sex of the baby can play a surprising role in gdm risk. The researchers found that mothers carrying male babies have a slightly higher risk of developing gdm because boys seem to have an adverse effect on the mothers’ glucose metabolism.

Consequently, mothers who develop gdm while carrying a girl — in the absence of this adverse influence of a boy — are seven per cent more likely than gdm mothers of boys to develop Type 2 diabetes before their second pregnancy. Dr. Retnakaran’s team is currently designing interventional trials aimed at modifying the risk of developing Type 2 diabetes, using a variety of strategies including short-term insulin therapy.

“ The doctors and nurses at Mount Sinai were all really, really good and calmed my fears. But they also reminded me to continue with what I’m doing or the diabetes could come back.”

V ICTORIA C HO

Victoria’s initial routine screening, which is recommended for all pregnant women between 24 and 28 weeks, involved drinking a sweet glucose drink in the doctor’s office, then having a blood test to measure blood sugar levels. They were high. A second test involved another glucose drink, this time after fasting, and further tests for blood sugar levels. Again, she “failed” the test, which confirmed she had gdm.

Victoria, just under 5’2” and with a prepregnancy weight of 125 pounds, wasn’t overweight. Nor was she sedentary —

They did. Like 60 per cent of women with gdm, Victoria was able to control the condition just through dietary and lifestyle changes. (The other 40 per cent require injections of insulin, which does not cross the placenta or affect the baby.)

In November 2015 she gave birth to a healthy seven-pound girl, Jaime Lillian, and since then she has dropped most of her pregnancy weight. “The doctors and nurses at Mount Sinai were all really, really good and calmed my fears,” says Victoria, whose follow-up testing three months after the birth showed no sign

Searching for improved treatments

Dr. Feig is now leading or co-leading two multi-centre, multinational trials.

The first, conceptt, is studying women with Type 1 diabetes to see if continuous glucose monitors can help improve outcomes for their pregnancies, which are typically high-risk. The second study, MiTy, is looking at whether adding the drug metformin to insulin for pregnant women with Type 2 diabetes will improve fetal outcomes and, over the long run, reduce obesity in the children.

Results from those studies aren’t in yet, but ongoing research into gdm will continue to improve the lives of women and their babies. “At Mount Sinai,” says Dr. Retnakaran, “women and infants are always a priority.”

“Gestational diabetes is telling you something very important about your future risk of a major disease, and it gives us an opportunity to intervene.�

DR. RAV I R ETNA K A R A N

Drs. Ravi Ratnakaran and Denice Feig

The promise of

precision medicine ´ KIEWICZ W R I T T E N B Y: V E R O N I K A I Z A B E L A B R Y S P H O T O S B Y: J O H N PA C K M A N

Less than half a century ago, a diagnosis of rheumatoid arthritis was like a premature death sentence.

It meant a life of restricted movement, disfigurement, severe chronic pain and hospitalization.

Back then, no one knew that it was actually an illness of the immune system — an immune system that, due to an imbalance triggered by genetics and the environment, became over-reactive and attacked itself. In the case of rheumatoid arthritis: a merciless attack on the tissues lining the joints.

Gold injections, which dampened the symptoms of disease for a short period of time, were then part of the gold standard of care, though doctors did not understand why they worked, nor did the injections stop the disease’s progression for most patients.

But since then, knowledge about the illness has come a long way. In the last two decades alone, an explosion of clinical trials has led to a broader array of medications that keep symptoms and disease progression at bay.

Perhaps what is most exciting is the potential of some of the research taking place at Sinai Health System to not only help match the right drug to the right patient, but to someday stop the disease from ever manifesting in those who are at greatest risk.

Erinn’s journey Erinn McQueen is one of many rheumatoid arthritis patients who thrives for a period of time on a medication, but for reasons unknown, reaches a point when the same medication eventually ceases to work.

A patient at Sinai for 17 years, her journey began at age 21 when she was a star player on her university’s varsity soccer team. All of a sudden, she felt chronically exhausted and in pain. After several misdiagnoses, she was finally diagnosed with rheumatoid arthritis, thanks to a test that recognized a known biomarker in her blood, which shows up in about 70 per cent of cases.

As her illness progressed over the last decade and a half, she has had to change medications five times. At her worst, she was unable to brush her own hair or tie her own shoes, and she had to undergo several surgeries to remove damaged and disfigured joints, including a hip replacement in her early 30s.

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“ Research is a big part of why I still have hope.”

— E RI N N MCQUE E N

“ As no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease.”

— S I R WI LLIAM OSLE R ( 184 9–1919)

But for a period of time in her late 20s, her illness entered into what is called a “remission state,” where her symptoms completely disappeared and she was able to go drug free long enough to have two healthy pregnancies. These drug-free remission states, although they can happen, are rare. More often, patients have what doctors call “low disease states,” where symptoms are kept at bay via medications.

For Erinn, knowing that researchers are working on groundbreaking new treatments continues to give her hope about her future.

“I will make you better” One of the first things Dr. Edward Keystone said to Erinn when he became her rheumatologist nearly two decades ago was: “I will make you better.”

Dr. Keystone, Director of The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease (rmcad), has always seen it as his role as a doctor to help improve people’s health. He vividly remembers his first job at the now-closed Wellesley Hospital in the 1970s.

It was a time when rheumatoid arthritis

Erinn has been a patient of Dr. Edward Keystone for nearly 20 years

SUPPORT ARTH RITIS RESEARCH FOUN DATION:

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patients were hospitalized and there was almost nothing that medicine could do for them.

Today doctors know that the disease is driven by inflammation-causing hormones that are released by the body’s immune cells — likely triggered by something in a person’s environment like bacteria, a virus or lifestyle factors such as smoking. The immune system normally protects the body from foreign invaders, but in autoimmune conditions, for unknown reasons, the immune system also attacks the body’s own tissues.

A new family of drugs that has emerged in the last 15 years called “biologics” has dramatically changed the landscape. Biologics — a class of protein-based drugs derived from living cells — act like targeted missiles that remove the inflammation-causing hormones from circulating in a person’s body.

With the hormones gone, symptoms subside, and debilitation is halted in its tracks.

But only a small percentage of patients are able to stay on the same biologic long term.

At the other end of the spectrum, for about 15 per cent of patients, none of the drugs available to date has ever worked. For the remaining patients, like Erinn, medicationhopping is the norm.

Even amidst our current technological advancements, picking the right medication for a patient is trial and error. “It’s like tossing a coin,” says Dr. Keystone. “Right now, there is no simple test that can tell us which medication is best for each individual patient. But with the research discoveries we are making today using precision or personalized medicine, I believe we will be able to do that within the next decade.”

One of the many initiatives Dr. Keystone is a part of is outcomes research. With funding from the National Institutes of Health in the U.S., rmcad is one of several centres following thousands of patients who researchers know are genetically susceptible to getting the disease based on genetics or biomarkers. To see if it is possible to eradicate the disease before onset, people who are not yet sick will be treated with medication. If the research proves successful,

Dr. Kathy Siminovitch

it will be a huge step forward for the promise of precision medicine — treating patients earlier, and more effectively.

But for those patients who are too far along with their illness to be treated this way, precision medicine can provide another beacon of hope.

Treating disease individually Sir William Osler, the father of modern medicine, once said: “As no two faces are the same, so no two bodies are alike, and no two individuals react alike and behave alike under the abnormal conditions which we know as disease.” This observation is a major focus of scientist Dr. Kathy Siminovitch’s research. Dr. Siminovitch, who is a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute and the Sherman Family Research Chair in Genomic Medicine, has already discovered many of the key genetic variants (mutations and abnormalities) that cause rheumatoid arthritis. Much of her recent work is focused on understanding the mechanisms of how an individual’s own genetic makeup causes a different manifestation of the same illness.

“To understand why patients have different responses to medications and to disease, we need to define their genetic and immunologic differences,” she says. “With this knowledge, we can start to define what the predictive biomarkers are for these variable outcomes.”

In collaboration with scientists at the University of Toronto and Hospital for Sick

Children, Dr. Siminovitch’s lab team has established a Centre for Immune Profiling and is capitalizing on new technology to search for genetic and immune cellular biomarkers that can be used to tailor, and optimize, treatment for individual patients.

Results of this research will help clinicians like Dr. Keystone match the right drug to the right patient at the right time. Which also means it will help patients like Erinn mitigate painful joint damage in the long run.

“Eventually,” says Dr. Siminovitch, “we want to cure people.”

Giving patients hope For Erinn, rheumatoid arthritis has changed her entire life.

Though she has had to abandon some of her earlier dreams, like playing sports competitively or pursuing a career in massage therapy, she remains optimistic about what she still can do. These days, it includes coaching her daughter’s basketball team and working to become a certified Pilates instructor. She is also a patient advocate, and speaks publicly about her experience with the illness.

“Things that were easy before my diagnosis, like climbing stairs or riding my bike, became very difficult,” she says.

“Ongoing research into new treatments has allowed me to enjoy these activities again, and I’m determined to live each day as best as I can. Research is a big part of why I still have hope.”

15

A connection formed by

Dr. Oscar Singer’s mind is a mystery. Most days the former physician sits in his wheelchair surrounded by colourful canvasses he once painted and books in several languages he once read, quietly watching sports on TV.

He can still feed himself, but he has trouble swallowing. On a good day, the 88-year old Holocaust survivor can read a newspaper and even say a few words in German, Hungarian or English. But nobody knows whether he understands the words. Does he have Alzheimer’s? Dementia? Parkinson’s?

Even his diagnosis is unclear.

“If I think about it,” says his wife, Eva, 83, sitting in the beautiful, antique-filled living room of their North York home, “I cry sometimes because he had a fantastic mind, and to see that going is very sad. He’s very sweet, a wonderful person.”

Oscar takes medications, but Eva doesn’t think they’ve done much good. That’s not a surprise. About a hundred drugs have been tested for Alzheimer’s and dementia and the vast majority have failed outright. A few improve symptoms for a while.

Dr. Graham Collingridge knows those statistics well. A world authority on the connection between memory and brain plasticity — the process by which the

mind reinvents itself — Dr. Collingridge participated in the research underpinning the commonly prescribed Alzheimer’s drug Memantine. Now, the British-born physiologist is building on the partial success of that drug — doctors tell him it can stave off memory loss for up to a year — to develop the science that he hopes will lead to a far more powerful version of it.

“We have to fully grasp the way memories are formed before we can understand why they’re lost,” says Dr. Collingridge, Senior Investigator at the Lunenfeld-Tanenbaum Research Institute (ltri), part of Sinai Health System. “I believe the key is in the power of plasticity. If the brain’s wiring is capable of change, then we’re capable of changing the destiny of neurodegenerative disease.”

The mystery of Oscar Singer’s mind is mirrored, frustratingly, by the increasingly complex puzzle of neurodegeneration itself. In the genomic era, with wholegenome sequencing, scientists are starting to understand just how individual a person’s disease can be. They’re now questioning whether Alzheimer’s is one disease or dozens, or even thousands. The more researchers peer into the brains of the afflicted, the more genetic mutations they identify — dna errors that could be a smoking gun in one person’s disease and a red herring in another’s. And the lines between diseases like dementia and

W R I T T E N B Y: H E I D I S I N G E R P H O T O S B Y: J O H N PA C K M A N

“ I cry sometimes because he had a fantastic mind, and to see that going is very sad.

He’s very sweet, a wonderful person.”

— EVA S I NGE R

Left: Eva and Oscar Singer in London on their wedding day, September 12, 1959.

Below: Eva and Oscar attending the wedding of their niece in Montreal in 1979.

showed that this stopped the synapses from getting stronger. A third neuroscientist, Richard Morris, then demonstrated that the same drug blocked the formation of new memories. On the strength of that discovery, Dr. Collingridge, together with Drs. Bliss and Morris, last year was awarded the Brain Prize, the world’s top honour for neuroscience.

Parkinson’s are blurring. There appears to be substantial overlap in the pathways used by the different illnesses of the mind, including psychiatric conditions and even ordinary depression.

To date, most researchers and drug companies have focused on the so-called “plaques and tangles” that typically appear in scans of Alzheimer’s brains. But nobody knows whether they’re a cause, a symptom or both. The latest hope for a treatment crashed last year, when a much-anticipated drug broke up the plaques but failed to significantly improve the symptoms of disease.

“It’s an optimistic time” All of this may sound hopelessly discouraging, but to Dr. Collingridge, these are exciting days for research into brain disease. Scientists are finally starting to understand the physiology behind these conditions, and he believes stepping back to basics will result in a very big step forward.

“It’s an optimistic time because we’re getting closer to understanding the underlying pathology” of brain disease, says Dr. Collingridge, who is also Chair of the Department of Physiology at the University of Toronto’s Faculty of Medicine.

The first of these breakthroughs occurred with the development of a theory that memories are formed at the connections 18

between nerve cells, called synapses. (“Cells that fire together, wire together,” is the shorthand explanation.) When the communication between two neurons is going well and there are no glitches, the connection between them gets stronger, allowing memories to be stored. Then it was discovered how synapses can get stronger or weaker in response to their activity. This process, says Dr. Collingridge, is now widely regarded as the best explanation for how memory works.

The first breakthrough came from the Canadian psychologist, Donald Hebb, and the second by fellow Brit Tim Bliss, who was a graduate student at McGill University. So perhaps it was fitting that Dr. Collingridge developed the third while he was a young researcher at the University of British Columbia in the 1980s.

Dr. Collingridge discovered the mechanism that makes the synapses get stronger or weaker: a tiny part of the nerve cell called the nmda receptor. He used a drug that blocked the receptor, and

Dr. Collingridge assumed that blocking the nmda receptor would be a bad thing: Wouldn’t you want brain signals to be firing strongly to create solid memories?

This turned out to be true. But to his surprise, Dr. Collingridge found there could be too much of a good thing. Not only was too little nmda receptor activity bad for memory and thinking, too much was also detrimental. The important thing was to normalize this receptor. The drug Memantine, now the frontline treatment for mid-to-late stage Alzheimer’s, emerged directly from this research and is the first to attack Alzheimer’s by working to regulate the nmda receptor.

In his lab, Dr. Collingridge is building on this first-generation research to understand more about the process of plasticity, and how to achieve it through tuning up or down those synapses in the brain. The goal is to develop a more effective version of Memantine. Meanwhile, only half of the molecules involved in memory have been identified; Dr. Collingridge is trying to understand more about how they work, and to discover new ones that could be the next drug targets.

The ltri is a “fantastic environment for research, both because of the outstanding

WHERE THE SEARCH FOR ANSWERS CONNECTS

basic science and particularly having worldleading experts in the sorts of molecules that I’m interested in,” he says. “Also, being embedded in a hospital connects our lab with patients in a way that we never had in the UK.” His own theory about the cause of Alzheimer’s revolves less around the buildup of toxic plaques and centres on those nerve connectors, the synapses.

In the healthy brain, we are able to prune away old, unused synaptic connections, like a gardener might do with dying roses. But in Alzheimer’s, something goes badly wrong in this process so that important connections — beautiful, live roses essential to the garden’s beauty — are pruned away too.

“You start chopping away at connections you don’t want to lose,” he says.

“Hold his hand. He’s still your father.”

Eva Singer has never met Graham Collingridge, but every day she gives her husband the drug he helped develop.

As a scientist herself (a chemical engineer in her native Hungary), she keeps an eye on Alzheimer’s research. Eva doesn’t believe that a blockbuster drug will emerge in time to help her husband, but she is confident that she can manage him at home with all-day help from aides provided by Sinai Health System’s home care partner Circle of Care, along with other agencies

and her son. She is so confident that she passed up opportunities to place Oscar in top facilities, and recently, she took his name off their waiting lists.

“Some Alzheimer’s and dementia patients can become aggressive, and their personality changes,” she says. “I must say that I’m lucky in a way that he is very easy and very sweet. I decided as long as I’m able to do it… I’m going to keep him at home. It’s better for him and he’s happy.

He does recognize me — he calls me by name. I’m a steady point in his life so I would not change this at all.”

Eva recalls when Oscar’s memory problems worsened five years ago, during a trip to Europe. After they returned, she gently suggested it was time to give up his position working one day a week with a North York physician. Oscar was 83, and had once been Chief of Paediatrics at Scarborough Centenary Hospital (now Rouge Valley Health System). It was a sad day: First he was going to lose his lifelong identity as a doctor. Next, would he lose his identity as a man, a father and husband?

still his voice and his smile and his sweet temperament. Not long ago, their eldest son, also a physician, visited from St. Louis. Oscar sat quietly, surrounded by his paintings of scenes from the past — houses he’s stayed in, the abstract paintings that are Eva’s favourites and a vibrant depiction of Piccadilly Circus from his time in England, after surviving the war and Bergen-Belsen concentration camp.

“I said, ‘Just sit next to him. Hold his hand, and I know that he recognizes you.

He can’t talk to you. You can’t talk to him and ask how are you, Dad? But just hold his hand. He’ll smile at you and he’ll know you’re there. He’s still your father.’”

But even today, he’s still Oscar to his wife. He still says a few words and it’s

In the healthy brain, we are able to prune away old, unused synaptic connections, like a gardener might do with dying roses.

But in Alzheimer’s, something goes badly wrong in this process so that important connections — beautiful, live roses essential to the garden’s beauty — are pruned away too.

Dr. Graham Collingridge

19

Dr. Howard Tenenbaum

Targeting gum disease

“ I gained confidence — I just got back to my life, all the things people take for granted.”

— S H I N SU GI N O

21

The mouth is a powerful window into the health of the human body: Inflammation of the gums can be associated with heart disease, gut health and autoimmune conditions. But the significance of these links is not understood or appreciated fully.

W R I T T E N B Y: H E I D I S I N G E R P H O T O S B Y: J O H N PA C K M A N

At the same time, diseases of the gums and teeth are often overlooked in medicine — and the suffering they cause is grossly underestimated. In the most extreme cases, even children can lose their teeth, causing lifelong struggles with depression, selfesteem and anxiety.

A new research centre, based at Mount Sinai Hospital, part of Sinai Health System, is seeking to understand the biology behind oral diseases and their links to systemic health — and to eventually customize treatments for people with these often debilitating conditions. The dentists and scientists associated with this novel centre believe their research could help illuminate the role inflammation plays in all human disease.

When it opens this spring, The Centre for Advanced Dental Research & Care will treat the gta’s most difficult cases of refractory periodontitis (a particularly treatment-resistant type of gum disease), as well as patients whose implants have failed them or are at risk of failing them. The idea is to create individualized treatments for patients, based on the patient’s own biological samples. This will create a seamless and thoroughly unique connection between the patient and the research lab.

Unlike physicians, dentists don’t typically order lab work like blood and saliva tests to diagnose inflammatory and other conditions. At the Centre, this testing will be routine.

“We’ll go from the clinic to the lab and eventually back to the clinic,” says 22

Dr. Howard Tenenbaum, Dentist-in-Chief at Sinai Health System, who will lead the Centre. “This is truly personalized medicine — developing powerful biological and laboratory testing to guide and monitor treatment.”

The Centre will combine laboratory research and patient care in real time, to create individualized treatments for people who need immediate help. The other major goal is to conduct research, then turn it into useful clinical tests and publish the findings so that they can be shared with the world.

The Centre, a partnership between Sinai Health System and the University of Toronto’s Faculty of Dentistry, is being established through the generosity of the Canadian dental management firm dentalcorp.

“We are passionate about improving oral health across the country and committed to advancing the field of dentistry,” says Graham Rosenberg, Chief Executive Officer of dentalcorp. “This partnership provides us the opportunity to support a cause that champions the care and health of Canadians, especially those who continue to suffer from complex and hard to treat conditions.”

“They improved my life dramatically” Many of Sinai’s dentistry patients have served as early models for what the Centre can do. Shin Sugino, a Toronto filmmaker, had terrible problems with his teeth starting as a child in Tokyo. By the time he got to Mount Sinai, Shin’s upper teeth were falling out. Every year he wore

a larger denture, but it never fit right. At restaurants, Shin worried about ordering anything too hard or chewy, like steak. He didn’t smile much either.

“To be 45 and walking around with a denture, your self-esteem goes down,” recalls Shin, now 70, from his Leslieville film studio.

The Sinai team replaced Shin’s entire upper row of teeth with implants placed within bone harvested from his hip.

Unfortunately, almost a third of the time, painful inflammation can develop around implants, increasing the potential for complete implant failure. When Shin began to develop these symptoms, he was treated with three medications not ordinarily used on his conditions, and they completely resolved Shin’s problems.

Today, Shin returns to the hospital every three months for careful monitoring and a deep cleaning. He’s not shy about smiling anymore. He proudly reveals a perfect set of worry-free upper teeth.

“I gained confidence — I just got back to my life, all the things people take for granted,” recalls Shin, who directs TV commercials for well-known Canadian companies.

“They improved my life dramatically.”

“ I use the mouth as my model system to try and understand the interplay between oral diseases and systemic health.”

— DR. M ICH AE L GLO GAU E R

Taming inflammation These innovative treatments are examples of the kind of work the Centre will do, in partnership with U of T researchers.

Dr. Michael Glogauer, a professor in the Faculty of Dentistry, will be a key player due to his work on oral health and the interactions between plaque and the immune system, which he considers the most critical aspect of gum health.

Dr. Glogauer tries to understand what causes and maintains the inflammation that causes so much destruction in gum diseases.

He focuses on neutrophils and macrophages (types of white blood cells) that cause inflammation while eliminating harmful bacteria in the mouth. (In healthy mouths, these immune cells are able to maintain health without overt inflammation.)

Recently, in trying to understand what goes wrong in severe gum disease, Dr. Glogauer made a key discovery: Different types of inflammation in the body are associated with changes in previously unknown types of neutrophils. These changes are detectable and a clinical test is being developed to identify when inflammation is waxing and

waning. This would instantly reveal whether a novel treatment being developed in the Centre is working. Currently, periodontists must wait several months to determine the success or failure of treatment.

With better diagnostic and monitoring tools, Dr. Glogauer also hopes to develop tests that pinpoint the cause of gum disease, along with severe gum recession and inflammation associated with implants. For one person, it may stem from immune system irregularities, and for another, it could be bacterial. These ideas are at the heart of the Centre’s goals towards the development of personalized dental and periodontal care.

Taming inflammation and understanding the immune system are keys to the entire body’s health. And Dr. Glogauer believes there’s no better place for examining these processes than the mouth, which contains abundant amounts of bacteria and neutrophils. And of course the mouth is easily and completely visible, unlike the rest of the body’s interior.

“I’m a periodontist, but I’m first and foremost a scientist,” he says. “I use the mouth as my model system to try and understand the interplay between oral diseases and systemic health.”

Perhaps the most obvious connection is between the mouth and the gut. The body releases 300 billion neutrophils every day — and this could be ten times higher for the 30 per cent of the population with gum disease.

cause disease, or what they do in the gut.

Moreover, Dr. Glogauer has shown in mice that the numbers and types of neutrophils in the gut mirror those in the mouth. In the future, he says, a simple oral rinse could test the effectiveness of treatment of a wide array of diseases such as colitis and other inflammatory diseases of the gut.

And that’s just the beginning.

“It’s now clear in the literature that there are significant and profound links between oral health and systemic health,” he says. “Oral diseases have been linked to cardiovascular diseases, like heart attack and stroke. It’s been linked to all sorts of cancers, and arthritis.”

Dr. Tenenbaum, too, is intrigued by the connection between inflammation in the mouth and disease in other parts of the body. Oral problems could be a sign, and perhaps even a cause, of other diseases.

“We’ll combine high-level treatment — as high as you can get — with biological sampling,” Dr. Tenenbaum says. “We may even create a biobank with those samples.

And then, we hope to use the knowledge gained from the study of patient samples to personalize treatment for patients with oral health conditions that were either just difficult to treat or even untreatable before.

There’s nothing like this anywhere.”

At least 10 per cent of these neutrophils end up in the mouth, and many are swallowed into the gut. Nobody knows whether these activated inflammatory cells

23

Shining a light on breast cancer W R I T T E N B Y: S A R A D A N I E L S P H O T O S B Y: J O H N PA C K M A N

At age 26, Jennifer Landa was the picture of radiant health.

A longtime runner, she led a healthy and active lifestyle and was full of boundless energy.

She had passed her recent physical with flying colours.

Then, a few months later, Jennifer discovered a lump in her breast during a regular selfexamination. She wasn’t worried, but she knew she should have it checked out because breast cancer was common in her family — both her maternal and paternal grandmothers and one of her grandfathers were diagnosed with and treated for the disease. And because of their family history, her mother had been monitored for years by the team at the Marvelle Koffler Breast Centre (mkbc) at Mount Sinai Hospital, part of Sinai Health System.

After an initial consultation and ultrasound with her doctor, Jennifer’s mother encouraged her to come to mkbc, Canada’s first dedicated multidisciplinary breast centre, for a second ultrasound. Jennifer took her mother’s advice and made an appointment, expecting a routine procedure.

Instead, the technician discovered three lumps: two in her breast, and a swollen lymph node. A surgeon consulted on the ultrasound and ordered a mammogram, mri and biopsy right away. Amid the flurry of activity and concern, Jennifer realized something was clearly wrong. She was diagnosed with stage 3 breast cancer, and learned that she had inherited a genetic mutation, known as brca2, that predisposes individuals who carry it to developing breast and ovarian cancers.

clearly aggressive, and they warned her that she might not live more than another five years.

Dr. Pamela Goodwin, Jennifer’s physician and Director of the mkbc, quickly implemented a treatment plan. Within days of her diagnosis, Jennifer began her first round of chemotherapy. Her treatment continued for the next year and half, involving surgery and multiple rounds of chemotherapy and radiation. In early 2015, Jennifer was given the all-clear by her doctors.

As Jennifer came to terms with this new diagnosis, she remained positive, continuing to live every day to the fullest and even making a bucket list of goals she wanted to achieve. Then, in early October, while at a Maple Leafs game with a friend, she began to experience unusual tremors in her left arm and leg. Within an hour she was vomiting and could barely walk.

Her elder brother Michael brought her to the emergency room at Mount Sinai, where clinical staff gave her anti-nausea medication to ease her vomiting. Rather than pursue further tests that night, she decided to wait for her previously scheduled appointment with Dr. Goodwin on the upcoming Tuesday.

Feeling grateful and energized, Jennifer jumped back into her very full life, spending time with her huge network of friends and family who had been such an incredible support system during her treatment. And she eagerly sought out ways to share her story and support Sinai Health Foundation in its mission to raise money for the mkbc to help other patients facing breast cancer diagnoses.

Jennifer’s cancer returns After more than a year of living cancerfree, Jennifer came back to Mount Sinai in August 2016 because she was having trouble breathing. A ct scan revealed that her cancer had returned, and had spread to her sternum, right rib cage, spine and right pelvis. Her doctors developed a treatment plan designed to slow the spread of her cancer and give her as much time as possible. But her cancer was

After working from home on Monday, Jennifer came in for her appointment with her arm and leg still twitching uncontrollably.

Dr. Goodwin immediately ordered a ct scan and admitted her to the hospital, where she also had an urgent mri. The twitching, the tests revealed, was due to a localized seizure caused by one of 10 tumours in her brain, the largest 3.5 cm in size.

After a few days in the hospital, Jennifer returned home, grappling with her latest diagnosis. Six weeks before, she thought she might live only another five years; now she learned she had just months left.

A search for new treatments Breast cancer researcher Dr. Daniel Schramek, Kierans/Janigan Cancer Research Scientist at the Lunenfeld-

P H O T O C R E D I T: B R I A N M O S O F F P H O T O G R A P H Y

“I was in disbelief,” Jennifer recalls. “It came out of nowhere.”

Tanenbaum Research Institute (ltri), is looking at ways to treat — and even prevent — hormone-induced breast cancers like Jennifer’s. During his doctoral work with Dr. Josef Penninger at the Austrian Academy of Sciences in his native Vienna, he discovered that rank ligand (rankl), a molecule that affects the immune system and controls bone development, plays a key role in driving hormone-induced breast cancer.

In the mammary glands, rankl causes cells to grow and divide rapidly, for example to induce lactation after a woman gives birth so she can breastfeed. Dr. Penninger suspected the function of rankl in the mammary gland may have evolved to help pull calcium from women’s bones to provide this nutrient to babies in breast milk. rankl’s dual function in balancing calcium during bone development and lactation (i.e., bone destruction) might also be the reason why women are also much more likely to develop osteoporosis, a condition resulting in brittle bones.

If breast tissue cells have the ability to destruct bone — to release calcium into breast milk — so too might breast cancer cells. But instead of releasing calcium, the cancer cell degrades the bone and divides

Since 2014, Jennifer has been a powerful patient ambassador for the Marvelle Koffler Breast Centre and Sinai Health Foundation.

P H O T O C R E D I T: D O U G N I C H O L S O N

Jennifer participated in the Estée Lauder Companies’ Breast Cancer Awareness campaign in September 2014

Jennifer speaking at Oakdale Golf fore the Cure in July 2015

Jennifer’s fundraising campaign launch event in December 2016: From left, Dr. Pamela Goodwin, Christopher Landa, Jennifer, Dr. Jaime Escallon and Michael Landa

P H O T O C R E D I T: R O S E M A R Y G O L D H A R

again and again, causing metastasis of the original breast cancer tumour to the bone.

This could help explain why breast cancer often spreads to the bones, particularly the rib cage and spine, as Jennifer’s cancer has done.

Dr. Schramek’s early research, published in Nature in 2010, demonstrated that blocking the rankl gene in patients with hormone-induced breast cancer could be an effective new approach to treatment.

Now, clinical studies that build off of his important discoveries are showing that a rankl-blocking drug called denosumab — originally approved by the U.S. Federal Drug Administration (fda) to treat osteoporosis — seems to also work in breast cancers.

Dr. Schramek also hopes that using denosumab to block rankl preventatively in patients who have a high risk of developing breast cancer could actually protect them from getting cancer at all.

And as a bonus, the drug would also protect patients from osteoporosis. Testing this theory in a mouse model that was bred with an inherited brca gene mutation, and thus an increased risk of developing breast cancer, Dr. Schramek worked with

Dr. Penninger and his team to use an antibody to block rankl — and found that it did indeed protect the mouse from getting breast cancer. The results from this study were just published in 2016, and Dr. Schramek, a co-author on the study, is excited by the potential of this approach: Because it’s already cleared the fda’s safety hurdles, denosumab could be used in the clinic to treat breast cancer patients within just a few years.

“Usually if you find a promising treatment in the lab, it takes 15 years before it’s available for clinical use,” Dr. Schramek explains. “If denosumab works, it could be available to patients in just a few years.

That’s really, really exciting.”

27

Studying late recurrence Since coming to the ltri in 2015, Dr. Schramek has joined the Hold‘em for Life Poker Charity Challenge project, a major breast cancer research initiative supported by the real estate, asset management and mining industries of Canada. Established by Dr. Goodwin, the team comprises scientists including Dr. Jim Woodgett, Koffler Director of the ltri, and Dr. Rama Khokha, an oncologist and Senior Scientist at the Princess Margaret Cancer Centre whose work has explained the exact role of rankl in mammary stem cell biology.

The Hold‘em for Life team has recently launched a long-term study driven by clinical observations in

MEET JENNIFER

• “ C O N N E C T I N G W I T H T H E R EA L J E N N ” • “ W H E R E T H E S EA R C H F O R A NS W E R S C O N N E C T S ” youtube.com/sinaihealthsystemca

the mkbc that most breast cancer deaths now seem to come from late recurrence — as many as 10 years after entering remission — in patients whose earlier cancer was treated effectively.

Nobody yet knows what drives late recurrence in these patients, but doctors at mkbc have observed that sometimes they have had some sort of injury — for example, a car accident, a broken bone, a surgery. At the site of the injury, the breast cancer relapses. The new Hold‘em for Life study, which will follow current breast cancer patients over the next ten years, will explore whether the data supports this theory.

Meanwhile, Dr. Schramek is taking the problem back to his mouse models. He suspects rankl is again a likely culprit in driving late recurrences in patients who have experienced some kind of injury or insult to the body.

“If a bone breaks, it has to be remodeled to heal.

That remodeling always involves rankl, and if you have a dormant cancer cell hanging around in the body, and it is exposed to a signal that tells usually dormant cells, for example, bone cells, to grow to heal a wound, that same signal could also awaken the sleeping cancer cell. An inflammatory wounding environment is a very rich environment for cancer to grow.”

This seamless integration of clinical and basic research demonstrates the value of having the ltri’s scientists so closely aligned with their clinical colleagues at Mount Sinai.

Dr. Daniel Schramek

“I need to talk to the clinicians,” says Dr. Schramek. “I would have never started this late recurrence project if I were not educated by fellow scientists and clinicians such as Dr. Goodwin and Dr. Khoka about the problems that affect their patients.”

“ The triple negative group is a small one, but it’s a heartbreaking group.”

— DR. DA N I E L S CH R A M E K

The deadliest subtype The early onset of Jennifer’s illness is unusual. While one in 9 Canadian women will develop breast cancer during her lifetime, typically the disease affects women in their late 50s and early 60s. Younger patients like Jennifer account for a much smaller percentage of hormone-induced breast cancers.

And yet younger women are more prone to developing a small but deadly subtype of the disease: triple negative breast cancer. Accounting for only 10 to 20 per cent of women who get breast cancer, triple negative breast cancer occurs at higher rates in women of colour and those who have the BRCA1 and BRCA2 mutations. Triple negative breast cancer patients are typically under 40, and the disease often appears in young mothers, shortly after breastfeeding.

Moved by the relative youth of the patients affected by this aggressive disease — and the lack of targeted treatment options for these women — Dr. Schramek is devoting much of his current work to learning more about how this devastating disease develops and what treatment approaches might be effective.

“The triple negative group is a small one,” says Dr. Schramek, “but it’s a heartbreaking group.”

Triple negative breast cancer is so called because these cancer cells lack receptors for the three most common drivers of breast cancer: estrogen, progesterone and human epidermal growth fact receptor 2 (HER2). Drugs developed to block these receptors to prevent cancer growth don’t work for these patients.

Dr. Schramek’s research, funded in part by Susan G. Komen, a leading breast cancer organization in the U.S., is focused on figuring out what drives the growth of these tumours. While genome-sequencing techniques have made it possible for scientists to identify mutations associated with a disease, it can’t pinpoint which of these mutations actually cause the disease.

To determine that, geneticists must take these sequencing insights and test them in model organisms whose cells behave similarly to human cells.

For Dr. Schramek, the tool of choice is the mouse model. “I’m absolutely convinced that we need genetic mouse models to understand how breast cancer behaves in the body,” he says.

“Cancer cell lines, which are restricted to a plastic plate and grown in an incubator, can’t tell you, for example, how a tumour spreads.”

Sequencing of triple negative breast cancer cells have not uncovered mutations that regularly appear from tumour to tumour. What it has shown is an increase in copy number alterations, suggesting that the tumours are genomically instable, and that some parts of the cells’ chromosomes and genes are repeated, while others are missing.

Dr. Schramek and his team are using mouse models to explore the role these alterations may have on triple negative tumour development. His team, including graduate student Ellen Langille, recreates the same deletions and amplifications pinpointed through sequencing in the mouse using a revolutionary gene-editing technology called clustered regularly interspaced short palindromic repeats (CRISPR).

CRISPR allows scientists to make targeted genetic alterations in actual tissue, and to evaluate the effects of many distinct alterations simultaneously.

The CRISPR technology, developed by scientists just five years ago, is an extraordinary advance for the field of genetics. In the past, geneticists could make a single genetic alteration in the germline of each mouse and then breed the mice to see the alteration expressed in the next generation. It took about two years and cost $100,000 to explore just one alteration, which may or may not prove to be a cause of disease. With the development of CRISPR, which allows scientists to literally cut the DNA at a chosen point to remove and/or insert targeted DNA, Dr. Schramek’s team has developed a unique methodology allowing them to make up to 600 genetic alterations just in the mammary glands of the mouse within five weeks, at one-tenth of the cost.

This means Dr. Schramek and his team can cover a lot of genetic ground in a much shorter period of time, and they can more quickly pursue further studies of molecules and mechanisms that prove likely to play a role in causing the disease. The sooner some of the mechanisms of the disease can be identified, the sooner Dr. Schramek’s team can begin searching for targeted treatments that will help stop the disease in its tracks.

And time is of the essence for women who are facing a triple negative breast cancer diagnosis. While chemotherapy, radiation and surgery can be successful in treating these tumours, the recurrence rate for the disease is especially high. Many patients relapse in as few as two or three years, and when they do, the cancer often spreads quickly from the breast to the lungs or the brain.

29

“Mini victories” Despite Jennifer’s devastating diagnosis, she has been characteristically positive and eager to accomplish as much as possible in the coming months.

“It’s all about the mini-victories that I can accomplish in the time I have left,” she says.

Chief among her goals is to share her story and the experience she has had as a patient at Mount Sinai to help raise money for breast cancer treatment and research. She is deeply grateful for everyone on her care team at mkbc who has been with her, taking care of her and fighting alongside her, every step of the way.

Jennifer was a special guest at Dinner with Scientists

“They even know me by name,” says Christopher, Jennifer’s youngest brother, who often accompanies her to appointments.

“You feel like a person, not a number. It’s amazing.”

“Jennifer has been a shining light,” says Dr. Goodwin. “She is strong and gracious and she has always chosen to focus on the positive, even when she is not feeling well. She is much loved and appreciated by the staff and other patients for her sense of humour, her joie de vivre and her unfailing ability to positively impact everyone around her. She has become an important spokeswoman and champion for our breast centre, the ltri and for countless other patients living with this unpredictable disease.”

In November, Jennifer and her brothers starred in a powerful video for Dinner with Scientists, presented by PearTree Financial, Sinai Health Foundation’s marquee fundraising event in support of the ltri. She also attended the event — wearing a glamourous gown chosen for the special occasion — with her brothers, where they saw the debut of the video alongside the event’s 400 guests.

P H O T O C R E D I T: A N N I E T O N G

P H O T O C R E D I T: N I C K L E E

“It’s the worst-case scenario, best case experience,” says Jennifer.

“Everyone at Mount Sinai has been amazing. I don’t have to think about what appointment to book next, they just organize everything. I walk in and everyone knows me by first name, they’re pulling my wristband out of the drawer as soon as they see me.

They don’t just treat me like that, they treat everyone like that.”

Jennifer with Dr. Pamela Goodwin, left, and Dr. Rowan Chlebowski, the inaugural recipient of the Jennifer Landa Breast Cancer Visiting Professorship

Jennifer is also leading her own fundraising campaign to raise money through her vast network of loved ones and supporters. To date, she has raised more than 75 per cent of her $150,000 goal to support an endowed visiting professorship that will allow the mkbc to bring international breast cancer leaders to Mount Sinai on a regular basis to ensure that the Centre remains at the forefront of cancer treatment and research.

Ultimately, Jennifer hopes her fundraising campaign will help bring hope to future patients.

Support Jennifer’s campaign: supportsinai.ca/jennlanda

“I want to help save other people,” says Jennifer. “That would be so cool. I think that’s the most amazing thing I can do with the time I have left.”

Community Corner DI N N E R WI TH S C I E N T IS T S EXP L OR E S HOW CO N N ECT I O NS F UE L SCI E NT I F I C DISCOV E RY

WA T C H “ W H E R E T H E S EA R C H F O R A N S W E R S C O N N E C T S ” PHOTO CRE DITS: N ICK LE E AN D D OUG N ICHOLSON

youtube.com/sinaihealthsystemca

Top: Dinner with Scientists 2016 at The Carlu Right: Guests listen to opening address by Joseph Mapa, Sinai Health Foundation CEO

On November 21, Sinai Health Foundation hosted its marquee event Dinner with Scientists presented by PearTree Financial for a crowd of more than 400 guests from the philanthropic and business community to benefit the Lunenfeld-Tanenbaum Research Institute (ltri), part of Sinai Health System and one of the top 10 biomedical research institutes in the world. This year’s event focused on Where Care Connects, the meeting point of patient care, research and the community.

“Tonight we capture the essence of connectivity and how it fuels discovery,” said Joseph Mapa, ceo of Sinai Health Foundation.

During the event, longstanding partner Scotiabank announced a $1 million gift to the ltri, which will be matched by the Tanenbaum Research Matching Endowment Fund created by Larry and Judy Tanenbaum and their family, doubling their impact.

Presenting Sponsor, PearTree Financial (left to right) Renee Bleeman, Ron Bernbaum and Marilyn Anthony, with guest speaker Arianna Huffington

The evening included a vip Reception hosted

by PwC and a keynote speech by Pulitzer Prize-winner for national reporting and founder of The Huffington Post and Thrive Global, Arianna Huffington about the

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COMMUNITY CORNER

importance of sleep, the science behind it and how lack of sleep affects our health (see her tips for better sleep on page 33).

Guests were also treated to an expert panel discussion by ltri investigators Dr. Graham Collingridge, Dr. Helen McNeill, Dr. Alexandre Zlotta and Dr. Rayjean Hung about how connections lead to discoveries. The panel was sponsored by Gluskin Sheff and moderated by acclaimed television host, author, researcher and journalist, Dr. Jennifer Gardy.

L I S T E N T O T H E EX P E R T P A N E L P O D C A S T:

http://bit.ly/dwspodcast

Top: Dinner with Scientists panel: Dr. Alexandre Zlotta, Dr. Rayjean Hung, panel moderator Dr. Jennifer Gardy, Dr. Graham Collingridge and Dr. Helen McNeill Left: Caroline Woodgett; Dr. Jim Woodgett, Koffler Director of Research, LTRI; Dr. Gary Newton, President and CEO, Sinai Health System; Jay Hennick, Board Member, Sinai Health System; Judy Tanenbaum, Event Co-Chair; and Lawrence Tanenbaum, Board Member, Sinai Health System

Left: Jay Hennick; Stacey Cynamon, Event Co-Chair; Dr. Gary Newton; David G. Cynamon, Board Co-Chair, Sinai Health Foundation; Brent Belzberg, Board Chair, Sinai Health System; Arianna Huffington; Joseph Mapa, CEO, Sinai Health Foundation; Howard Sokolowski, Board Co-Chair, Sinai Health Foundation; and the Honourable Linda Frum, Board Member, Sinai Health System

Right: Front row – Jennifer Landa, Michael Landa, Ray Walsh, Joyce Walsh; Back row – Christopher Landa, Charlotte Thuot, Dr. Andrea Jurisicova, Marilyn Ida Howse, John Howse, Fabiana Bacchini and Dr. Stelios Nikolakakis

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WHERE THE SEARCH FOR ANSWERS CONNECTS

3 TIPS FOR BETTER SLEEP Sleep is not optional, Arianna Huffington, founder of The Huffington Post and Thrive Global, told guests during a keynote address at Dinner with Scientists, presented by PearTree Financial, a fundraising event in support of the Lunenfeld-Tanenbaum Research Institute.

According to Arianna, though we often think of sleep as “wasted” time, for the brain it is actually a time of frenetic and essential activity

Here are Arianna’s TOP 3 tips to help ensure the most restful, restorative sleep possible every night

1

When we’re asleep, the brain cleans up all the toxins that have accumulated throughout the day If that doesn’t happen it can have consequences for our short- and long-term memory and our overall health

2

In fact, sleep deprivation is linked to:

Create nightly rituals and routines that help you transition to sleep, much as parents do when putting their children to bed. Whether your rituals last an hour or just five minutes, they will help signal to the body and brain that it is time to slow down and prepare for sleep

Turn off all devices and charge them outside of your bedroom to prevent them from disrupting your sleep and help stem the urge to reach for them during the night

HIGH BLOOD PRESSURE DIABETES CANCER ALZHEIMER’S DISEASE DEPRESSION and ANXIETY

3

Make simple changes to create an environment conducive to sleep: • Make sure your bedroom is as dark as possible with no outside or blinking lights penetrating the darkness • Keep your bedroom between 18 to 20.5 degrees to avoid overheating during the night

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POWE R O F M OV E M E N T Arthritis Research Foundation (ARF) has recently partnered with Sinai Health Foundation as the exclusive fundraisers for arthritis and related autoimmune diseases across Sinai Health System. Power of Movement (POM) was the first fundraising event under the Sinai umbrella. Over the years, ARF’s enthusiastic community has raised over $2 million.

This year, participants gathered on Sunday, March 5 at locations in Toronto, KitchenerWaterloo and Whitby to enjoy a morning of yoga and raise funds in support of ARF. The Toronto event was held at Ryerson University and emceed by Global News’s Farah Nasser and Alan Carter.

Yoga was led by Paul Galloro of YogaFit Canada, Glenn Julien of YOGAthletix and Salimah Kassim-Lakha of YogaVision, and a delicious lunch was provided by The Country Kitchen.

1: Partcipants do yoga 2: Global News’s Farah Nasser and Alan Carter, Event Emcees

3 P H O T O C R E D I T: ROBI N SHARP PHOTO GRAPHY

P H O T O C R E D I T: D A N O S A D S T U K

P H O T O C R E D I T: M A N G O S T U D I O S

3: Paul Galloro of YogaFitCanada leads yoga

ASSET MANAG E M E NT I N D U S T RY H OL D‘E M F O R L I F E C HARI TY C HA L L E N G E W H E N : October 27, 2016 W H A T: The fifth annual fundraiser supports a collaborative

program of integrated breast cancer research at Mount Sinai Hospital. The event is attended by top executives from Canada’s leading asset management and finance firms who come together for a unique evening of charity, fun and friendly competition.

W H O : Guests enjoying a game of poker

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“THE GALA” IN SUPPORT OF THE PANOV PROGRAM W H E N : January 28, 2017 W H A T: The third annual gala for young professionals in support

of The Panov Program, a program which aims to bring precision chemotherapy to Canada W H O : Adam Panov, Event Organizer

WHERE THE SEARCH FOR ANSWERS CONNECTS

T H E S I NAI SO I RE E W H E N : October 29, 2016 P H O T O C R E D I T: T O M S A N D L E R

P H O T O C R E D I T: N I C K L E E

W H A T: A Día de los Muertos-themed

Halloween party hosted by Future Sinai in support of the Slaight Family Labour & Delivery Unit at Mount Sinai W H O : 1: Rebecca Laramee, Future Sinai Chair,

and Simonne Horwitz and Melissa Tayar, Event Co-Chairs

2: A vampire scopes out a day-of-the-dead guest

T H E GREAT JEWE LLE RY H E IS T W H E N : October 28, 2016 W H A T: The sixth annual fundraiser in

support of complex care at Bridgepoint Active Healthcare, featuring a luncheon at The Ritz-Carlton hotel and exclusive silent and live auctions of tempting jewels donated by leading designers, jewellers and style-setters.

W H O : Laura Dottori-Attanasio, Sinai

SE RV I N G F O R S I NA I On March 26, Serving for Sinai, an all-day co-ed “Battle of the Business” volleyball tournament and networking event raised more than $220,000 in support of the Lunenfeld-Tanenbaum Research Institute. Over 300 players came together for this inaugural event, which featured several VIP guests, including nine Olympian players, some of whom just placed 9th in the world. There was a great feature match, which pitted past Olympians against future Olympians. Young professionals represented their companies across three divisions, RioCan Real Estate Division, Vice Media Technology Division and Torys LLP Professional Services Division.

P H O T O C R E D I T: S T E P H E N S A G E R

Health Foundation Board Member and Event Executive Chair; Veni Iozzo, 2016 Event Chair; Amanda Lang, Emcee; Susan Rimmer, Event Executive Chair

1: Canadian past and present Olympians in a match 2: Zack Belzberg, Event Co-Chair; Dr. Gary Newton; David G. Cynamon; Jesse Abrams and Carly Bardikoff, Event Co-Chairs

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Launching this spring with the philanthropic and leadership support of dentalcorp, the new Centre for Advanced Dental Research & Care, a clinical and research partnership between Sinai Health System and the University of Toronto’s Faculty of Dentistry, will address some of the most misunderstood and complex dental, periodontal and orofacial conditions. Led by Dr. Howard Tenenbaum, Dentistin-Chief at Sinai Health System, and located at Mount Sinai Hospital, the Centre’s goal is to develop world-leading diagnostics and care standards to put Canada at the vanguard of patient dental care. The Centre is the first of its kind in North America, and will bring together evidencebased clinical care and discovery science research, providing the opportunity to facilitate the best new discoveries for patient care.

The Centre will also explore the psychosocial implications of complex oral health conditions.

Dr. Bruce Freeman, Co-Director, Facial Pain Unit, Department of Dentistry, Mount Sinai Hospital; Dr. Howard Tenenbaum; Graham Rosenberg, CEO, dentalcorp; Dr. Daniel Haas, Dean, U of T Faculty of Dentistry; Dr. Andrew Meikle, Chief Dental Officer, dentalcorp

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H E R SH E N H O RN F AM I LY I NV EST S I N SI NAI ’ S F UT URE

P H O T O C R E D I T: A N N I E T O N G

dentalcorp H E L P S LA U N C H TH E C E N T R E FOR ADVAN C E D D E N TA L RE SEARC H & C A R E A T SI NAI H EAL TH S Y S T E M

Siblings Steven, Barbara and Hartley Hershenhorn in the Hennick Family Wellness Gallery

It’s not every day that three siblings make Sinai Health System part of their estate plans — but that’s exactly what happened in the Hershenhorn family.

Following in the footsteps of their parents, Zelda and Kelly Hershenhorn, Barbara, Hartley and Steven have been dedicated supporters of the Mount Sinai Hospital community for thirty years. Steven and Hartley were born at Mount Sinai, and all of them, including several family members, have been cared for at the hospital. Over the years, Steven and Hartley have volunteered with the Mount Sinai Classic Golf Tournament, and Steven, previously on Mount Sinai’s Board of Directors, now serves on the Finance Committee of Sinai Health Foundation’s Board of Directors. In 2002, following their father Kelly’s passing the year before, the Hershenhorns donated a menorah custom-made for the hospital in his memory to give patients, visitors and staff the opportunity to gather together each night of Hanukkah to light the candles and celebrate.

it’s going to Mount Sinai, it’s going to help someone in need.”

Hartley and Barbara decided to leave gifts in their wills to support the Lunenfeld-Tanenbaum Research Institute (ltri), the research arm of Sinai Health System. Hartley created the Hartley Hershenhorn Research Award Fund, which will rotate annually between supporting prostate, orthopaedics and neurodegenerative diseases — all crucial areas of research as our population ages.

Barbara’s gift supports highest-priority research needs at the ltri. “Research helps both immediately and for many generations going forward. Scientists are always discovering new things and finding better methods of dealing with existing conditions,” she says.

“Cures and quality of life improvements all come from research,” Hartley adds.

The Hershenhorns’ generosity stems from their belief in the mitzvah of giving. Explaining their philosophy, Steven quotes Albert Einstein: “‘It is Steven and Hartley made plans to leave bequests to every man’s obligation to put back into the world Mount Sinai 25 years ago. Steven chose to make an at least the equivalent of what he takes out of it.’” unrestricted gift, which allows hospital leadership the flexibility to apply the funds wherever the Hartley adds, “If one person is inspired by what organization’s future needs are greatest. we’ve done as a family and decides to make a gift, big or small, that’s a great accomplishment.”

“There are many areas within the hospital that need funding,” explains Steven. “As long as

Sinai 365

WHERE CARE CONNECTS 365 Moments from across Sinai Health System

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Connections are at the heart of Sinai Health System, a leading integrated health system with complementary strengths in hospital-based care, rehabilitation, home care and research. Whether you are delivering care, discovering new ways to care or receiving care, there is a complex spectrum of emotions that patients, families and staff experience. These 365 spontaneous moments captured at Bridgepoint Active Healthcare, Circle of Care, Lunenfeld-Tanenbaum Research Institute and Mount Sinai Hospital each tell the unique stories about how care connects us. Discover how these worldclass institutions are creating a seamless journey for the people they care for.

Follow us on Instagram @sinaihealthsystemto

31 CONTACT is the largest photography event in the world, and a premiere cultural experience in Canada, with over 1,500 artists in 200 exhibitions and happenings throughout the month of May in the Greater Toronto Area. Founded in 1997, CONTACT is a not-for-profit organization dedicated to celebrating and fostering the art and profession of photography.

1 Bridgepoint Active Healthcare 1 Bridgepoint Drive, M4M 2B5 Hours: Monday-Sunday 8 a.m. to 8 p.m.

Mount Sinai Hospital Joseph & Wolf Lebovic Health Complex 600 University Avenue, M5G 1X5 Hours: Monday-Sunday 8 a.m. to 8 p.m.

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This CONTACT exhibition began as an Instagram project intended to provide an inside look at the day-today activities at Sinai Health System.

With one daily post since April 1, 2016, the exhibition focuses on our commitment to patient care, and tells the unique stories that only a health care environment can offer. Patients, families and staff have graciously provided us with consent to use their images in demonstrating where care connects across our organization.

+ YOU =

RESEARCH to our

that bring

T O SU P P O RT C O N N E C T E D C A R E A T S I NA I H EALT H SY ST E M, PLEASE V ISI T:

supportsinai.ca/sinaihealth

Hospital + Rehabilitation + Home Care + Research Sinai Health System is comprised of Bridgepoint Active Healthcare; Circle of Care; Lunenfeld-Tanenbaum Research Institute and Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex — from healthy beginnings to healthy aging. Sinai Health Foundation raises and stewards funds to support Sinai Health System. The generous support of our community fuels everything we do from connected care to scientific discovery.