I n d e x

Message from the Director, Child Health Research, Research Institute of the McGill University Health Centre (RI-MUHC) ...... 2

Message from the Executive Director and Chief Scientific Officer, Research Institute of the McGill University Health Centre (RI-MUHC) ...... 3

Message from the Chair of the Advisory Group on Research to the Council for Services to Children and Adolescents (CSCA) ...... 4

Message from the Associate Executive Director of the Montreal Children’s Hospital (MCH) . . . . .5

Our Researchers ...... 6

New Recruit ...... 7

Science That Connects ...... 8

Honours and Distinctions ...... 9

Glen site of the McGill University Health Centre (MUHC) under construction, spring 2013 Investigator and Trainee Awards ...... 10

Researcher Profiles: • Geneviève Bernard, MD, M.Sc., FRCPC ...... 12 • Nancy Braverman, MD, M.Sc...... 13 • Pierre Lachapelle, PhD ...... 14 • Pia Wintermark, MD ...... 15 • Michele Zappitelli, MD, M.Sc...... 16

Selected Publications ...... 17

Funding • Major Benefactors of Research Programs at the Montreal Children’s Hospital (MCH) ...... 20 • External Funding ...... 21

Committees ...... 22

Acknowledgements ...... 22

Our Research Community ...... 22

The new Montreal Children's Hospital (MCH; Block B)

Entrance, MCH

Life-saving therapies for sick children depend on the wealth of connections made in our child health research programs at the Montreal Children’s Hospital. “Every day ... we search for the connections that help us understand the bases for children’s diseases and make new outcomes possible.”

Message from the Director, Child Health Research, Research Institute of the McGill University Health Centre (RI-MUHC)

Every day, in research programs at the Montreal Children's Hospital (MCH), we search for the connections that help us understand the bases for children's diseases and make new outcomes possible. Whether it is connections between patients and researchers (bedside to bench and back for prevention and treatment), those with our colleagues in maternal–fetal medicine and in the community, or Jacquetta Trasler, connections between fundamental and clinical researchers tackling disorders across MD, PhD the lifespan, our reward is in hearing of better endings to stories for young patients coping with health challenges. Director, Child Health Research, RI-MUHC at the Montreal Making connections across time, this year Dr. Beth Foster and colleagues showed Children's Hospital (MCH) that the risk of death for children on dialysis for severe kidney disease is dramaticall y reduced compared with the outlook 20 years ago. MCH clinical researcher Dr. Pia Wintermark made waves in the medical community with her work on a cooling technique that improves outcomes for newborns with brain and eye injuries, and she has connected with MCH fundamental researcher Dr. Pierre Lachapelle to design new treatments for affected children.

Dr. Charles Scriver and Mr. Arnold Steinberg received the 2012 Medal of Honour from the Health Research Foundation for pioneering the addition ofVitamin D to milk in Quebec in the early 1970s, a masterstroke that reduced cases of nutritional rickets in children from 1,000 per year to almost none today.This example of science connecting with community invites speculation about the advances we will be celebrating years from now, given the major projects on genomics and personalized medicine underway in MCH laboratories in 2012-2013.

With the 2015 move to new facilities at the Glen in sight and a head start on next year’s task of reorganizing our child health research programs, we sincerely thank our funding partners, including the FRQS, CIHR, CFI, MCH Foundation and Foundation of Stars, as well as our Advisory Group on Research, for helping us bring together the people most likely to make extraordinary connections for the betterment of children’s health.

2 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS “Today, we have strong evidence that the factors influencing human life in utero and in early childhood also shape an individual’s future health.”

Message from the Executive Director and Chief Scienti fic Officer, Research Institute of the McGill University Health Centre (RI-MUHC)

Child health research is not contained by age boundaries; it extends from the development of the embryo and fetus into adult life. Research is also fluid in geography, crossing territorial boundaries and calling for collaboration across borders.

Today, we have strong evidence that the factors influencing human life in utero and Vassilios Papadopoulos, in early childhood shape an individual’s future health. I take this occasion to D.Pharm., PhD congratulate our researchers at the Montreal Children’s Hospital for their indefatigable contributions to improving the lives of patients, from newborns to Executive Director and adolescents and, by extension, the lives of the adults they will become. Toward Chief Scientific Officer, this purpose, as is demonstrated in this year’s report, child health research at the RI-MUHC RI-MUHC fully integrates basic, clinical and evaluative research methods to tackle a broad range of diseases.

With the opening of the new Glen site hospital facilities ahead and renovations anticipated at the Montreal General Hospital, the outlook for research at the MUHC is full of promise. Collaboration has always been vital to scientific inquiry, and at this juncture it is more important than ever that our researchers, many of whom will soon be united under a new roof, nurture new connections that will accelerate scientific advances, consolidate their skills, stimulate collegiality and enrich their intellectual curiosity.

State-of-the-art facilities and equipment will help us to extend the limits of knowledge in health research, integrate that knowledge into clinical practice and teaching, and contribute to better patient care for children, adults and families.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 3 - “Every year, new areas of research at the MCH open avenues to a greater understanding of health problems.”

Message from the Chair of the Advisory Group on Research to the Council for Services to Children and Adolescents (CSCA)

Any oversight of child health research at the Montreal Children’s Hospital (MCH) brings to light the enormous difference that such programs make in providing positive outcomes for the health problems addressed by collaborative researchers. Programs of such calibre provide common ground upon which the ideas of scientists, clinicians and caregivers connect.And every year,new areas of Gretta Taylor research at the MCH open avenues to a greater understanding of health problems Chambers, and improved treatment of existing conditions.This year was no exception. CC, OQ BA, DLitt In neonatology, MCH studies into the causes and consequences of brain and eye Chair of the Advisory Group injuries in sick babies are increasing their chances of improved outcomes. on Research to the CSCA Researc h in pediatric nephrology has made headway in evaluating acute kidney injury, a common condition in children. Our medical geneticists and neurologists Chancellor Emerita, are studying inherited disorders caused by defects in genes in order to develop McGill University treatments where none are in place today. The list of medical conditions and fields of study is as impressive as the list of MCH clinical and basic researchers devoted to the healthy development of children.

A successful connection of scientific inquiry with clinical care, financial support and administrative effectiveness is once again very much to the fore in the Advisory Group’s assessment of what research programs at the MCH have accomplished in 2012-2013.We are all proud to be associated with so valuable a contribution to children’s health.

4 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS “The Montreal Children’s Hospital wouldn’t be where it is today without the passion and ingenuity of our researchers.”

Message from the Associate Executive Director of the Montreal Children’s Hospital (MCH)

The Montreal Children’s Hospital wouldn’t be where it is today without the passion and ingenuity of our researchers. Their expertise in various fields of research and medicine allows us not only to save lives, but to improve the lives of our patients in important ways.

A feature in our internal magazine, Chez nous, related how this year one of our Martine Alfonso former patients had the opportunity to meet the researcher who helped change her life. Truly an example of “science that connects,” as you will see on page 8 of Associate Executive Director, this report, Karine’s entire world changed after Rosemarie Grabs discovered a Montreal Children’s Hospital gene mutation in Karine that allowed her to switch from daily insulin injections of the MUHC to oral medication.This experience not only gives a human face to the world of child health research, but helps connect the dots between the hard work that goes on in our laboratories and how it directly impacts the lives of our young patients and their families.

Knowing the depth of commitment to helping sick children that is shared by all members of the MCH community,I am confident our dual role as leaders in child health research and medicine will continue to grow and expand. As the preparations escalate for our move to the Glen in 2015, we can count on our new home helping to create even stronger ties and better opportunities.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 5 - OUR RESEARCHERS

By Axis of the Research Institute of the MUHC

Cancer Axis Health Roman Jednak Lily Hechtman Sharon Abish Outcomes Axis Loydie Jerome-Majewska Cécile Rousseau Kolja Eppert Maala Bhatt Jean-Martin Laberge Adam Fleming Franco Carnevale Aimée Ryan Musculoskeletal David Mitchell Evelyn Constantin Michael Shevell Disorders Axis Janusz Rak Geoffrey E. Dougherty Laurie Snider Sarah Campillo Sasha Dubrovsky Gaëlle Chédeville Cardiovascular Mohamed El-Sherbiny Infection and Reggie Hamdy Diseases and Patricia Fontela Immunity Axis Claire LeBlanc Critical Care Axis Sylviane Forget Reza Alizadehfar Maryam Oskoui Dominic Chalut Fatemeh Jafarian Moshe Ben-Shoshan Jean A. Ouellet Adrian Dancea Michael S. Kramer Martin Bitzan Celia Rodd Ronald Gottesman Lucyna Lach Bruce Mazer Neil Saran Sam Shemie Patricia Li Christine McCusker Rosie Scuccimarri Dominique Shum-Tim Stephen Liben Jane McDonald Blair Newell Whittemore Mary Ellen Macdonald Dorothy L. Moore Neurosciences Davinia Withington Annette Majnemer Earl Rubin Axis Samara Zavalkoff Romain Mandel Ernest G. Seidman Geneviève Bernard John J. Manoukian Marie-Emmanuelle Dilenge Endocrinology, Meranda Nakhla Medical Isabelle Gagnon Diabetes, Jesse Papenburg Genetics and Shuvo Ghosh Nutrition Hema Patel Genomics Axis Krista L. Hyde and Kidney Robert W. Platt Nancy Braverman Pierre Lachapelle Diseases Axis Caroline Quach Kathleen Glass Bernard Rosenblatt Najma Ahmed Saleem Razack Nada Jabado Teresa Valois Gomez Sherif Emil Janet E. Rennick Feige Kaplan Pia Wintermark Bethany Foster Patricia Riley Robert K. Koenekoop Preetha Krishnamoorthy Christina Rosmus John Mitchell Respiratory Laurent Legault Rima Rozen Health Axis Véronique Morinville Human Charles R. Scriver Robert Brouillette Constantin Polychronakos Reproduction and Jacquetta Trasler Larry C. Lands Gloria S. Tannenbaum Development Axis Johanne Morel Michele Zappitelli Sam J.Daniel Mental Illness Francisco Noya Cynthia Gates Goodyer and Addiction Pramod Puligandla Paul R. Goodyer Axis Charles Rohlicek Indra Gupta Eric Fombonne Guilherme Sant'Anna Brian Greenfield Researchers Affiliated with the Montreal Children’s Hospital

Jeffrey Atkinson Karen A. Brown Chantal Frigon Maria Ramsay Claudette Bardin John Paul Capolicchio Mirko Gilardino Ana Maria Sant’Anna Robert Barnes Aurore Côté Josée Lavoie Melvin Schloss Marie Josée Béland Joëlle Desparmet Serge Melançon Christo I. Tchervenkov Lorraine Bell Giosi Di Meglio Klaus Minde Ted Tewfik Margaret Berry Alessandra Duncan José Luis Montes Farhan Bhanji Ricardo Faingold Lily Ha-Nam P. Nguyen Adam Bretholz Jean-Pierre Farmer Thérèse Perreault

6 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS NEW RECRUIT

Kolja Eppert, PhD

Assistant Professor, Department of Pediatrics, and Canada Research Chair in Cancer Stem Cell Biology, McGill University Scientist, Division of Pediatric Hematology-Oncology, Montreal Children’s Hospital of the MUHC

RI-MUHC Axes: Cancer; Medical Genetics and Genomics

New recruit Dr. Kolja Eppert is a biologist who studies cancer stem cells. He aims to develop new therapeutics for childhood acute myelogenous leukemia, a type of cancer in which approximately 55% of young patients still lose their battle to survive despite aggressive therapy. Dr. Eppert holds a doctorate in molecular and medical genetics from the University of Toronto, where he also completed postdoctoral studies in affiliation with the University Health Network, Ontario.

Pedal for Kids 2013: Montreal Children's Hospital research team

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 7 - SCIENCE THAT CONNECTS

At the Montreal Children’s Hospital (MCH), research comes out of the laboratory to connect with the world. And sometimes, it brings kids into the laboratory to connect with science.

Experiments that lead to individualized medicine Former MCH patient Karine (pictured left) meets Rosemarie Grabs, who identified a gene mutation in Karine that allowed her to switch from daily insulin injections to oral medication as a teenager.This change had a very positive outcome for Karine.

Because the MCH is a research hospital and home to Dr. Constantin Polychronakos’s Endocrine Genetics Laboratory, where Rosemarie works as a research associate, patients like Karine benefit from diagnostic tests that would not be cost-effective to run routinely in clinic. A grant from the Canadian Gene Cure Foundation allowed Rosemarie to screen DNA samples for a rare variant of type 1 diabetes.

Research personnel rarely meet with a subject of their tests and hear about the dramatic long-term improvement made possible by their experiments. Thanks to Dr. Laurent Legault, Karine’s former treating physician, and to Karine’s mother Hélène, this research success story came to light and Rosemarie met Karine in 2013.

Connecting with our future scientists in the commu nity Fourteen-year-old Laurent Mailloux (left) spent one summer afternoon collecting his prize in Dr. Jacquetta Trasler’s Developmental Genetics Research Laboratory.The secondary 2 student at Collège Mont-Royal earned a personalized workshop conducted by research associate Josée Martel (right), along with his Junior Gold medal in the 2013 regional finals of Super Expo-Sciences Hydro-Québec.The workshop culminated in a hands-on task, the genotyping of four patients’ DNA for cystic fibrosis.

“I understand better now what DNA is, and its role in genetic diseases like colour blindness, the subject of my Expo-Sciences project,” said Laurent, following the session. The unusual prize idea came from MCH physician and researcher Dr. Caroline Quach, this year’s scientific chair of the Expo-Sciences regional final. Dr. Quach, like Dr. Trasler, believes that mentoring future scientists is a priority for child health research, and students deserve opportunities that ignite their interests early on.

8 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS HONOURS AND DISTINCTIONS

2012 2013

Dr. Sam Daniel received the Ameri- Dr. Lily Hechtman received the canAcademy of Otolaryngology–Head Transcontinental Research Award of and Neck Surgery Foundation Honor Excellence from the Montreal Chil- Award, given to members in recogni- dren’s Hospital Foundation.This prize tion of their volunteer contributions is awarded to a researcher whose to the Academy and its Foundation. initiatives have made a unique and sig- nificant contribution to pediatric care.

Ms. Xiaoyang Liu, an MD/PhD stu- dent in Dr. Nada Jabado's brain Dr. Nada Jabado headed a research tumour research laboratory, received team from the RI-MUHC that re- the August 2012 Étudiants-chercheurs ceived a major investment for an étoiles award from the Fonds de innovative project on the genomic recherche du Québec–Santé in the biomarkers associated with pediatric Fonds Santé [Health Fund] category. glioblastoma, a form of incurable cancer.This project will aim to develop new therapeutic approaches that are more targeted and therefore more Dr.Constantin Polychronakos was effective to improve quality of life for these young patients. elected a Canadian Academy of Health Entitled Geno mics and Personalized Health, the competition Sciences Fellow, one of the highest was organized by Genome Canada in partnership with the honours for individuals in the Cana- Canadian Institutes of Health Research (CIHR). The project dian health sciences community. is co-led by Dr. Jacek Majewski, associate professor in the Department of Human Genetics at McGill University, and Dr.Tomi Pastinen, associate professor and Canada Research Dr. Charles Scriver received the Chair in Human Genomics at McGill University. 2012 Medal of Honour from the Health Research Foundation for his outstanding contribution to health Dr. Rima Rozen was awarded the sciences and public health innovation. Queen Elizabeth II Diamond Jubilee With Mr.Arnold Steinberg, the joint Medal in recognition of her dedicated recipient of the award, he worked to service to her peers, to her commu- ensure the addition of vitamin D to milk in Quebec starting nity and to Canada. in the early 1970s, reducing the occurrence of nutritional rickets in children from over 1,000 per year to almost none. He and Mr. Steinberg also collaborated on the development of the National Food Distribution Centre for the Manage- ment of Patients with Hereditary Metabolic Disease. This work has had extraord inary impact on the health of young Canadians.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 9 - INVESTIGATOR AND TRAINEE AWARDS

Investigators Doctoral Research Awards

Canada Research Chair Canadian Institutes of Health Research Tier 1 • Deshayne Fell • Eric Fombonne • Adam Fontebasso • Ernest Seidman • Gabriel Kaufman • Xiaoyang Liu Fonds de recherche du Québec–Santé • Denise Keiko Shikako-Thomas National Researcher • Robert Platt Fonds de recherche du Québec–Santé Clinical Research Scholar–Senior • Sabrina Cavallo • Indra Gupta • Michelle Collins • Nada Jabado • Noémi Dahan-Oliel Clinical Research Scholar–Junior 2 • Esterina D’Asti • Evelyn Constantin • Élise Fortin • Bethany Foster • Dong Anh Khuong Quang • Isabelle Gagnon • Nathalie Magnus • Caroline Quach • Grzegorz Sobieraj • Michele Zappitelli Clinical Research Scholar–Junior 1 Natural Sciences and Engineering • Geneviève Bernard Research Council • Meranda Nakhla • Mireille Schnitzer • Janet Rennick • Pia Wintermark Social Sciences and Humanities Research Scholar–Junior 1 Research Council • Krista Hyde • Sara Quirke • Mary Ellen Macdonald • Tialee Ouimet Networks of Centres of Excellence/Allergen Master’s Research Awards Emerging Clinician-Scientist • Moshe Ben-Shoshan Canadian Institutes of Health Research Post-doctoral Fellowship • Karine Choquet • Mena Farag • Suna Jung Canadian Institutes of Health Research • Melodie Mograss Fonds de recherche du Québec–Santé • Mena Farag • Justine Lee Garner Natural Sciences and Engineering Research Council of Canada • Brennen Geller

10 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS In MCH laboratories, we connect the possibilities.

$9 M External peer-reviewed funding 335 Peer-reviewed publications 114 Graduate students and postdocs 50 Investigators with external peer-reviewed funds Embryology Laboratory, MCH RESEARCHER PROFILES

Advancing Leukodystrophy Research

Dr. Geneviève Bernard is an expert on pediatric neurodegenerative and neurogenetic disorders. Her focus is on leukodystrophies, a group of inherited white matter diseases of the brain. Children with leukodystrophies face serious challenges. The disease typically presents as developmental regression in a previously healthy child.This leads to progressive neurological deterioration, Geneviève Bernard, increasing and significant disabilities, and ultimately death. An estimated 40% of MD, M.Sc., FRCPC children affected by these disorders remain without a precise diagnosis despite extensive investigations. Neurosciences and Medical Genetics and Genomics Axes A clinician-scientist, Dr. Bernard treats young patients from across the province Assistant Professor (Clinical) at the specialized leukodystrophy clinic at the Montreal Children’s Hospital for of Pediatrics and of which she is responsible. Her research has so far aimed at helping these children Neurology and Neurosurgery, and their families by investigating the clinical and imaging characteristics of the McGill University diseases along with genetic causes. Division of Pediatric Neurology, Already a recognized leader in leukodystrophy research, this young investigator Montreal Children’s Hospital of has established valuable local, national and international collaborations. She and the MUHC her collaborators have discovered two genes responsible for causing a subset of leukodystrophies called Pol III-related leukodystrophies. Building on these key findings, Dr. Bernard’s laboratory is working on the identification of new forms of leukodystrophies and on characterizing the newly described Pol III-related subset. New perspectives will include the study of epidemiology, natural history and quality-of-life impacts, with the ultimate objective of improving care.

12 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS Investigating Peroxisome Disorders in Children

Dr.Nancy Braverman studies a group of inherited disorders caused by defects in genes responsible for the proper function of peroxisomes. These important components of cells contain the enzymes needed to metabolize lipids, or fatty acids.

Peroxisome disorders involve defects in the assembly of the peroxisome itself, Nancy Braverman, or in specific enzymes located in the peroxisome. In severe forms, children may MD, M.Sc. be born with malformations of the brain, eye or kidney. In milder forms, a progressive postnatal disease causes children to develop hearing and visual loss, Medical Genetics and leading to their classification as deaf-blind and/or having adrenal gland insufficiency, Genomics Axis leukodystrophy or chronic lung disease.Non-genetic loss of peroxisome functions Associate Professor of Human has been associated with some common as well as rare neurodegenerative Genetics and of Pediatrics, disorders. McGill University Division of Medical Genetics, Dr.Braverman’s laboratory investigates how these enzyme defects cause disease Montreal Children’s Hospital in the brain and lung in order to develop treatments, as there are none yet. Cell of the MUHC transplants, gene therapy studies and the evaluation of drug therapies are underway, along with the clinical trial of one drug already en route from bench to bedside.To provide patients and their families with better management guidelines and to establish endpoints for future clinical trials, the laboratory has established an international patient registry and natural history study.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 13 - RESEARCHER PROFILES

Diagnosing the Earliest Signs of Retinal Disorders

Dr. Pierre Lachapelle’s research team is working on approaches to studying the functional integrity of the human visual system, from the retina to the visual cortex.The laboratory also characterizes animal models of such human retinal diseases as retinopathy of prematurity, age-related macular degeneration, and retinitis pigmentosa. It aims to better explain the pathogenesis of these Pierre Lachapelle, PhD retinopathies and ultimately to explore new therapeutic strategies.

Neurosciences Axis One project involves the use of newly developed mathematical tools to extract Professor of Ophthalmology and clinical information from residual electroretinograms (ERGs).The ERG is essential Associate Member, Department not only for the diagnosis, but also for the proper management of patients affected of Neurology and Neurosurgery, by a variety of retinal dystrophies. In effect, the ERG is to the retina what the Faculty of Medicine, McGill electrocardiogram is to the heart. It identifies the electrical response evoked by University the retina in response to a light stimulus of adequate energy. Pediatric Ophthalmology, Using residual ERGs to model the progression of severe and debilitating Montreal Children’s Hospital retinopathies could make it possible to construct a disease/symptoms of the MUHC classification system.This would lead to a more accurate diagnosis and prognosis for the affected patients. Such a system is also likely to have significant impact on patient management, now that clinical trials exploring therapeutic avenues for the eradication of such retinopathies are underway.

14 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS Improving Outcomes for Asphyxia in Babies

Dr.PiaWintermark conducts research into the causes and consequences of brain and eye injuries in sick babies. She aims to develop innovative strategies to prevent or repair such injuries and improve the future for these babies.

At birth, some babies experience a condition called asphyxia in which their brain and other organs do not receive enough blood and/or oxygen. This is a life- Pia Wintermark, MD threatening condition that often causes permanent damage, including cerebral palsy, mental retardation or loss of vision. Total body cooling, or hypothermia, is Neurosciences Axis the new standard of care for these babies, and Dr.Wintermark is investigating and Cardiovascular and why this treatment works in some cases and not in others. Critical Care Axis Assistant Professor of Pediatrics, Specifically, her laboratory is studying measurements of brain blood flow during McGill University the first days of life in babies treated with hypothermia for this condition. If such Neonatology, Montreal Children’s measurements permit the early identification of babies at risk of developing brain Hospital of the MUHC injury despite cooling treatment, their treatment could be tailored optimally. Dr. Wintermark is also studying the impact of asphyxia on the eye and vision in human babies and in an animal model of this condition.Additionally, in the animal model, she is testing new therapeutic interventions that could lead to less severe brain and eye injuries.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 15 - RESEARCHER PROFILES

Evaluating Acute Kidney Injury in Children

Because the kidneys are often the “innocent bystanders” affected by other diseases or conditions, between 15 and 82% of children admitted to the intensive care unit have acute kidney injury, or AKI. Low blood pressure, severe infection, and certain medications essential to the treatment of serious diseases—but toxic to the kidneys—are common causes. Dr. Michele Zappitelli’s research aims to Michele Zappitelli, better understand AKI in order to detect the disease earlier, lessen the most MD, M.Sc. severe short-term risks and improve patients’ long-term health.

Endocrinology, Diabetes, Dr. Zappitelli’s clinical research laboratory is characterizing the disease by Nutrition and Kidney evaluating definitions and performing studies to assess the effect of AKI on various Diseases Axis outcomes in several diagnostic populations. Included are patients on nephrotoxic Assistant Professor of Pediatrics medications, patients undergo ing cardiac surgery and critically ill patients. and Associate Member, Department of Epidemiology, His latest projects examine the long-term outcomes of AKI in cardiac and Biostatistics and Occupational non-cardiac critically ill patients, and in children treated for cancer with cisplatin. Health, and Division of The aim is to evaluate whether AKI is a risk factor for chronic kidney disease Experimental Medicine, and whether new AKI biomarkers of renal tubular damage can be used to McGill University better diagnose patients at risk of chronic kidney disease. Other projects focus on discovering and characterizing novel AKI urine protein biomarkers for Director, Dialysis and AKI diagnosis. Apheresis Program, Pediatric Nephrology, Montreal Children’s Hospital of the MUHC

16 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS SELECTED PUBLICATIONS (FROM OVER 300)

2012

Alos N, Grant RM, Ramsay T, Halton J, Cummings EA, Miettunen PM, Dubrovsky AS, Foster BJ, Jednak R, Abish S, Atkinson S, Barr R, Cabral DA, Cairney E, Couch R, Dix DB, Mok E, McGillivray D. Visibility of Fernandez CV, Hay J, Israels S, Laverdiere C, Lentle B, Lewis V, the urethral meatus and risk of Matzinger M, Rodd C, Shenouda N, Stein R, Stephure D, Tab. High urinary tract infections in uncircum- incidence of vertebral fractures in children with acute cised boys. Cmaj 184(15):E796-803, 2012. lymphob lastic leukemia 12 months after the initiation of Ducharme FM, Morin J, Davis GM, Gingras J, Noya FJ. High physician therapy. J Clin Oncol 30(22):2760-7, 2012. adherence to phenotype-specific asthma guidelines, but Bitzan M, Babayeva S, Vasudevan A, Goodyer P, Torban E. TNF alpha large variability in phenotype assessment in children. Curr pathway blockade ameliorates toxic effects of FSGS plasma Med Res Opin 28(9):1561-70, 2012. on podocyte cytoskeleton and beta3 integrin activation. Dufresne D, Hamdan FF, Rosenfeld JA, Torchia B, Rosenblatt B, Michaud Pediatr Nephrol 27(12):2217-26, 2012. JL, Srour M. Homozygous deletion of Tenascin-R in a patient Bonner SM, Pietropaolo SL, Fan Y, Chang Y, Sethupathy P, Morran MP, with intellectual disability. J Med Genet 49(7):451-4, 2012. Beems M, Giannoukakis N, Trucco G, Palumbo MO, Solimena M, Elliott I, Kadis DS, Lach L, Olds J, McCleary L, Whiting S, Snyder T, Smith Pugliese A, Polychronakos C, Trucco M, Pietropaolo M. Sequence ML. Quality of life in young adults who underwent resective variation in promoter of Ica1 gene, which encodes protein surgery for epilepsy in childhood. Epilepsia 53(9):1577-86, 2012. implicated in type 1 diabetes, causes transcription factor Emil S, Gaied F, Lo A, Laberge JM, Puligandla P, Shaw K, Baird R, Bernard autoimmune regulator (AIRE) to increase its binding and C, Blumenkrantz M, Nguyen VH. Gangrenous appendicitis in down-regulate expression. J Biol Chem 287(21):17882-93, 2012. children: a prospective evaluation of definition, bacteriology, Brossard-Racine M, Shevell M, Snider L, Belanger SA, Majnemer A. histopathology, and outcomes. J Surg Res 177(1):123-6, 2012. Motor skills of children newly diagnosed with Attention Galera C, Bouvard MP, Lagarde E, Michel G, Touchette E, Fombonne E, Deficit Hyperactivity Disorder prior to and following treat- Melchior M. Childhood attention problems and socioeco- ment with stimulant medication. Res Dev Disabil 33(6):2080-7, Br J Psychiatry 2012. nomic status in adulthood: 18-year follow-up. 201(1):20-5, 2012. Bruijning-Verhagen P, Quach C, Bonten M. Nosocomial rotavirus Garnier D, Magnus N, Lee TH, Bentley V, Meehan B, Milsom C, infections: a meta-analysis. Pediatrics 129(4):e1011-9, 2012. Montermini L, Kislinger T, Rak J. Cancer Cells Induced to Express Cao XL, Zhang J, Goodyer CG, Hayward S, Cooke GM, Curran IH. Mesenchymal Phenotype Release Exosome-like Extracellu- Bisphenol A in human placental and fetal liver tissues lar Vesicles Carrying Tissue Factor. J Biol Chem 287(52):43565- collected from Greater Montreal area (Quebec) during 72, 2012. 1998-2008. Chemosphere 89(5):505-11, 2012. Iglesias DM, El-Kares R, Taranta A, Bellomo F, Emma F, Besouw M, Carpe N, Mandeville I, Kho AT, Qiu W, Martin JG, Tantisira KG, Raby Levtchenko E, Toelen J, van den Heuvel L, Chu L, Zhao J, Young YK, BA, Weiss ST, Kaplan F. Maternal allergen exposure reprograms Eliopoulos N, Goodyer P. Stem cell microvesicles transfer the developmental lung transcriptome in atopic and normo - cystinosin to human cystinotic cells and reduce cystine responsive rat pups. Am J Physiol Lung Cell Mol Physiol accumulation in vitro. PLoS One 7(8):e42840, 2012. 303(10):L899-911, 2012. Koenekoop RK, Wang H, Majewski J, Wang X, Lopez I, Ren H, Chen Y, Cleveland J, Rousseau C. Mental health impact of detention Li Y, Fishman GA, Genead M, Schwart zentruber J, Solanki N, Traboulsi and temporary status for refugee claimants under Bill C-31. EI, Cheng J, Logan CV, McKibbin M, Hayward BE, Parry DA, Johnson Cmaj 184(15):1663-4, 2012. CA, Nageeb M, Poulter JA, Mohamed MD, Jafri H, Rashid Y. Mutations Dix D, Cellot S, Price V, Gillmeister B, Ethier MC, Johnston DL, Lewis in NMNAT1 cause Leber congenital amaurosis and identify V, Michon B, Mitchell D, Stobart K, Yanofsky R, Portwine C, Silva M, a new disease pathway for retinal degeneration. Nat Genet Bowes L, Zelcer S, Brossard J, Traubici J, Allen U, Beyene J, Sung L. 44(9):1035-9, 2012. Association between corticosteroids and infection, sepsis, La Piana R, Vanderver A, van der Knaap M, Roux L, Tampieri D, Brais and infectious death in pediatric acute myeloid leukemia. B, Bernard G. Adult-onset vanishing white matter disease due (AML): results from the Canadian infections in AML research group. to a novel EIF2B3 mutation. Arch Neurol 69(6):765-68, 2012. Clin Infect Dis 55(12):1608-14, 2012.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 17 - SELECTED PUBLICATIONS

2012 (continued)

Li P, To T, Guttmann A. Follow-up care after an emergency Papenburg J, Hamelin ME, Ouhoummane N, Carbonneau J, department visit for asthma and subsequent healthcare Ouakki M, Raymond F, Robitaille L, Corbeil J, Caouette G, utilization in a universal access healthcare system. Frenette L, De Serres G, Boivin G. Comparison of risk J Pediatr 161(2):208-13 e1, 2012. factors for human metapneumovirus and respiratory Li SC, Torok KS, Pope E, Dedeoglu F, Hong S, Jacobe HT, Rabi- syncytial virus disease severity in young children. J Infect novich CE, Laxer RM, Higgins GC, Ferguson PJ, Lasky A, Baszis Dis 206(2):178-89, 2012. K, Becker M, Campillo S, Cartwright V, Cidon M, Inman CJ, Jerath Puligandla PS, Laberge JM. Congenital lung lesions. Clin Peri- R, O'Neil KM, Vora S, Zeft A, Wallace CA, Ilowite NT, Fuhlbrigge natol 39(2):331-47, 2012. RC. Development of consensus treatment plans for Saran N, Varghese R, Mulpuri K. Do femoral or salter innom- juvenile localized scleroderma: a roadmap toward inate osteotomies improve femoral head spheri city in comparative effectiveness studies in juvenile localized Legg-Calve-Perthes disease? A metaanalysis. Clin Orthop scleroderma. Arthritis Care Res (Hoboken) 64(8):1175-85, Relat Res 470(9):2383-93, 2012. 2012. Tran D, Vaudry W, Moore DL, Bettinger JA, Halperin SA, Scheifele Liu XY, Gerges N, Korshunov A, Sabha N, Khuong-Quang DA, DW, Aziz S [and/for IMPACT investigators]. Comparison of Fontebasso AM, Fleming A, Hadjadj D, Schwartzentruber J, children hospitalized with seasonal versus pandemic Majewski J, Dong Z, Siegel P, Albrecht S, Croul S, Jones DT, Kool influenza A, 2004-2009. Pediatrics 130(3):397-406, 2012. M, Tonjes M, Reifenberger G, Faury D, Zadeh G, Pfister S, Jabado Vehik K, Cuthbertson D, Boulware D, Beam CA, Rodriguez H, N. Frequent ATRX mutations and loss of expression in Legault L, Hyytinen M, Rewers MJ, Schatz DA, Krischer JP adult diffuse astrocytic tumors carrying IDH1/IDH2 and [and/for TEDDY, TRIGR, Diabetes Prevention Trial-Type 1, and TP53 Mutations. Acta Neuropathol 124(5):615-25, 2012. Type 1 Diabetes TrialNet Natural History Study Groups]. Marcil V, Sinnett D, Seidman E, Boudreau F, Gendron FP, Beaulieu Performance of HbA1c as an early diagnostic indicator JF, Menard D, Lambert M, Bitton A, Sanchez R, Amre D, Levy E. of type 1 diabetes in children and youth. Diabetes Care Association between genetic variants in the HNF4A 35(9):1821-5, 2012. gene and childhood-onset Crohn's disease. Genes Immun Wilchesky M, Ernst P, Brophy JM, Platt RW, Suissa S. 13(7):556-65, 2012. Bronchodilator use and the risk of arrhythmia in COPD: Massoud AH, Guay J, Shalaby KH, Bjur E, Ablona A, Chan D, part 1: Saskatchewan cohort study. Chest 142(2): Nouhi Y, McCusker CT, Mourad MW, Piccirillo CA, Mazer BD. 298-304, 2012. Intravenous immunoglobulin attenuates airway inflam- Wintermark P. The role of brain MR scanning in the new- mation through induction of forkhead box protein born. Paediatrics and Child Health 22(4):155-159, 2012. 3-positive regulatory T cells. J Allergy Clin Immunol 129(6):1656-65 e3, 2012. Yeung JP, Kloda LA, McDevitt J, Ben-Shoshan M, Alizadehfar R. Oral immunotherapy for milk allergy. Cochrane Database Morin MP, Quach C, Fortin E, Chedeville G. Vaccination Syst Rev 11:CD009542, 2012 [Electronic Publication]. coverage in children with juvenile idiopathic arthritis followed at a paediatric tertiary care centre. Rheuma - Zappitelli M, Coca SG, Garg AX, Krawczeski CD, Thiessen tology (Oxford) 51(11):2046-50, 2012. Heather P, Sint K, Li S, Parikh CR, Devarajan P [and/for TRIBE- AKI Consortium]. Morinville VD, Husain SZ, Bai H, Barth B, Alhosh R, Durie PR, The association of albumin/creatinine Freedman SD, Himes R, Lowe ME, Pohl J, Werlin S, Wilschanski ratio with postoperative AKI in children undergoing cardiac surgery. Clin J Am Soc Nephrol 7(11):1761-9, 2012. M, Uc A [and/for INSPPIRE Group]. Definitions of pediatric pancreatitis and survey of present clinical practices. J Pediatr Gastroenterol Nutr 55(3):261-5, 2012. Ouimet T, Foster NE, Hyde KL. Auditory global-local pro- cessing: effects of attention and musical experience. J Acoust Soc Am 132(4):2536-44, 2012.

18 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS 2013

Benini R, Dagenais L, Shevell MI. Normal imaging in patients McDonald-McGinn DM, Fahiminiya with cerebral palsy: what does it tell us? J Pediatr S, Revil T, Nowakowska BA, Suhl J, 162(2):369-74 e1, 2013. Bailey A, Mlynarski E, Lynch DR, Yan Ben-Shoshan M, La Vieille S, Eisman H, Alizadehfar R, Mill C, Perkins AC, Bilaniuk LT, Sullivan KE, Warren E, Joseph L, Morris J, Clarke A. Anaphylaxis treated in a Cana- ST, Emanuel BS, Vermeesch JR, Zackai dian pediatric hospital: Incidence, clinical characteristics, EH, Jerome-Majewska LA. Hemi - triggers, and management. J Allergy Clin Immunol 132(3):739- zygous mutations in SNAP29 741 e3, 2013. unmask autosomal recessive conditions and contribute to Cherkasova M, Sulla EM, Dalena KL, Ponde MP, Hechtman L. atypical findings in patients Developmental course of attention deficit hyperactivity with 22q11.2DS. J Med Genet disorder and its predictors. J Can Acad Child Adolesc Psychi- 50(2):80-90, 2013. atry 22(1):47-54, 2013. Mitsnefes MM, Laskin BL, Dahhou M, Dancea A, Justino H, Martucci G. Catheter intervention for Zhang X, Foster BJ. Mortality risk Can congenital heart disease at risk of circulatory failure. among children initially treated J Cardiol 29(7):786-95, 2013. with dialysis for end-stage kid- Gdalevitch M, Kasaai B, Alam N, Dohin B, Lauzier D, Hamdy RC. ney disease, 1990-2010. Jama The effect of heparan sulfate application on bone forma- 309(18):1921-9, 2013. tion during distraction osteogenesis. PLoS One 8(2):e56790, Niles KM, Yeh JR, Chan D, Landry M, Nagano MC, Trasler JM. 2013. Haploinsufficiency of the paternal-effect gene Dnmt3L Gupta IR, Baldwin C, Auguste D, Ha KC, El Andalousi J, Fahiminiya results in transient DNA hypomethylation in progenitor S, Bitzan M, Bernard C, Akbari MR, Narod SA, Rosenblatt DS, Ma- cells of the male germline. Hum Reprod 28(2):519-30, 2013. jewski J, Takano. ARHGDIA: a novel gene implicated in Oskoui M, Coutinho F, Dykeman J, Jette N, Pringsheim T. J Med Genet 50(5):330-8, 2013. nephrotic syndrome. An update on the prevalence of cerebral palsy: a system- Horwood L, Nguyen LH, Brown K, Paci P, Constantin E. African atic review and meta-analysis. Dev Med Child Neurol American ethnicity as a risk factor for respiratory com- 55(6):509-19, 2013. JAMA Otolaryngol plications following adenotonsillectomy. Ouellet J, Odent T. Animal models for scoliosis research: Head Neck Surg 139(2):147-52, 2013. state of the art, current concepts and future perspective Kaczmarek J, Kamlin CO, Morley CJ, Davis PG, Sant'anna GM. applications. Eur Spine J 22 Suppl 2:S81-95, 2013. Variability of respiratory parameters and extubation Pham DN, Leclerc D, Levesque N, Deng L, Rozen R. beta, beta- Arch Dis Child Fetal readiness in ventilated neonates. Carotene 15,15'-monooxygenase and its substrate beta- Neonatal Ed 98(1):F70-3, 2013. carotene modulate migration and invasion in colorectal Lands LC, Stanojevic S. Oral non-steroidal anti-inflammatory carcinoma cells. Am J Clin Nutr 98(2):413-22, 2013. Cochrane drug therapy for lung disease in cystic fibrosis. Waissbluth S, Daniel SJ. Cisplatin-induced ototoxicity: Database Syst Rev 6:CD001505, 2013. transporters playing a role in cisplatin toxicity. Hear Res Liu S, Joseph KS, Lisonkova S, Rouleau J, Van den Hof M, Sauve R, 299:37-45, 2013. Kramer MS. Association between maternal chronic condi- Weiss MJ, Bhanji F, Fontela PS, Razack SI. A preliminary study tions and congenital heart defects: a population-based of the impact of a handover cognitive aid on clinical Circulation 128(6):583-9, 2013. cohort study. reasoning and information transfer. Med Educ 47(8):832-41, Matos-Miranda C, Nimmo G, Williams B, Tysoe C, Owens M, Bale 2013. S, Braverman N. A prospective study of brachytelephalangic chondrodysplasia punctata: identification of arylsulfatase E mutations, functional analysis of novel missense alleles, and determination of potential phenocopies. Genet Med 15(8):650-7, 2013.

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 19 - F U N D I N G (01/04/2012–31/03/2013)

Major Benefactors of Research Programs at the Montreal Children’s Hospital (MCH)

Donation fromThe Montreal Children’s Donation from the Foundation of Stars: Hospital Foundation: $5,137,984 $594,422 Generous support from donors committed to child The Foundation of Stars supports children’s health health enabled The Montreal Children’s Hospital research in Québec to give our children the chance Foundation to make disbursements of $5,137, 984 in to grow up healthy. support of child health research in 2012–2013. The Foundation of Stars is the primary source of non- Among the major contributors were the J. Armand governmental funding for research on children’s diseases, Bombardier Foundation, the Cole Foundation, Ray including orphan diseases, in Québec. Every dollar given Monahan Holdings, the Montreal Children’s Hospital to pediatric researchers is used to advance research with Research Endowment Fund, Judith and Charles Mappin, the aim of improving the quality of life of sick children Pedal for Kids, the Research Institute of the MUHC’s and their families. Special Fund, Shire,TD CanadaTrust,LouieTrakakis and a number of loyal groups and individuals. Their gifts led to For 35 years, the Foundation of Stars has cultivated significant advances in child health research in such areas a successful research environment at the MCH with such as oncology, allergies and mental health. establish ment and project support for investigators, bursaries for trainees and vital laboratory equipment. The Montreal Children’s Hospital Foundation’s Best Care These funds assist with the recruitment of investigators for Children Campaign has raised $105 million for the and help leverage innovative pilot research projects in cons truction of our new hospital and its new Research preparation for submission to federal and provincial Institute home on the Glen Campus. funding agencies for ongoing financial support. The Foundation of Stars is also proud to help the MCH realize one of its most valuable investments: training tomorrow’s Website: childrenfoundation.com child health researc hers.

Website: foundationofstars.ca

20 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS External Funding Recognized by the Fonds de recherche du Québec—Santé

4,938,795 Canadian Institutes of Health Research 964,872 Fonds de recherche du Québec—Santé 764,083 National Institutes of Health (U.S.) 592,742 Networks of Centres of Excellence of Canada 317,260 Canada Research Chairs Secretariat 208,133 Natural Sciences and Engineering Research Council of Canada 200,741 Genome Quebec 138,315 Sick Kids Foundation 100,570 Social Sciences and Humanities Research Council of Canada 99,770 The Canadian Cancer Society Research Institute 86,877 Foundation Fighting Blindness (Canada) 82,962 Canadian Diabetes Association 81,991 Ministère des Finances et de l’Économie (QC) 73,833 Dairy Farmers of Canada (QC) 69,032 Cystic Fibrosis Canada 62,295 The Kidney Foundation of Canada 60,208 Max Bell Foundation 47,655 United States Army Medical Research and Material Command 37,204 Ministère de la Santé et des Services sociaux (QC) 35,000 Talecris Biotherapeutics 26,578 Fonds de recherche du Québéc—Société et culture 20,000 Canadian Cancer Society 16,456 Heart and Stroke Foundation of Québec 13,440 Fonds de recherche du Québéc—Nature et les technologies 13,067 Ontario Neurotrauma Foundation 10,411 Canadian Dermatology Foundation 9,908 Autism Speaks (U.S.) 5,444 National Cancer Institute of Canada 3,748 Institut de recherche Robert-Sauvé en santé et en sécurité du travail 3,029 Heart and Stroke Foundation of Canada

$ 9,084,421

2012–2013 ANNUAL REPORT RI MUHC AT MCH | 21 - COMMITTEES

Advisory Group on Program Steering Research to the Council Committee for Services to Children Geneviève Bernard and Adolescents Hugh Clarke Gloria Tannenbaum, PhD, (right) receives a Gretta Chambers (Chair) Evelyn Constantin tribute from colleagues for her superlative management of the Research Seminar Program Phil Gold Bethany Foster at the MCH for 25 years (1988-2013). Martine Alfonso Paul Goodyer Michel Lanteigne Nada Jabado François Laurin Michael Kramer Acknowledgements David M. McEntyre Patricia Monnier This report was produced by Alison Burch of the Administrative Services of the RI-MUHC at Marianna Newkirk Robert Platt the Montreal Children’s Hospital. Thanks are Rose Goldstein Constantin Polychronakos due to many colleagues who were generous Jacquetta Trasler Aimée Ryan with their time and expertise, including Danuta Jacquetta Trasler Ry lski for her indispensable advice; André Simard and Melanie Cotiangco for statistics; Management Committee Vincenzo Comm Design Inc. for creative and Jacquetta Trasler (Chair) RI-MUHC Health and production services; and Sylvie Sahyoun for Robert Brouillette Safety Committee, translation. A very warm thank you to the Jean-Pierre Farmer MCH Site families who shared photographs of their Bethany Foster Aimée Ryan (Chair) children: Charlie, Darius, Delphine, Élodie, Laurent, Matheos, Michael, Nektario, Philip and Larry Lands Cynthia Gates Goodyer Pierre-Yves. Nada Jabado (Co-chair) Janusz Rak Dan Citra Charles Rohlicek Marie De Lorimier Our Research Community Aimée Ryan Adam Fontebasso The Research Institute of the McGill University Health Centre (RI-MUHC) at Michael Shevell Sarn Jiralerspong the Montreal Children’s Hospital (MCH) Micheline Ste-Marie Caroline Lebrun is composed of over 100 researchers and over Daniel Leclerc 100 graduate students and post doctoral fellows Fellowship Training Brian Meehan engaged in a broad spectrum of basic, clinical and evaluative research. Committee Janusz Rak Janusz Rak (Chair) Dac Hien Vuong Our research community constitutes the Nancy Braverman Hana Zouk pediatric site of the RI-MUHC, a world- Robert Brouillette renowned biomedical and health-care hospital research centre. Located in Mo ntreal, Quebec, Paul R. Goodyer Canada, the RI-MUHC is the research arm of Christine McCusker the MUHC, the university health centre Caroline Quach affiliated with the Faculty of Medicine at McGill University. Graduate Studentship The RI-MUHC is supported in part by the Committee Fonds de recherche du Québec—Santé Aimée Ryan (Chair) (FRQS). Evelyn Constantin Cynthia Gates Goodyer Nada Jabado Our website: thechildren.com/research Robert Platt Constantin Polychronakos

© 2014 Research Institute of the McGill University Health Centre at the Montreal Children’s Hospital 22 | CHILD HEALTH RESEARCH: SCIENCE THAT CONNECTS