2 | 2011-2012 IRCM ANNUAL REPORT |3 The IRCM: a biomedical research institute located in the heart of Montréal
4 | 2011-2012 IRCM ANNUAL REPORT |5 DISCOVERING T R E AT I N G 36 researchers – IRCM research professors 16,000 yearly visits at the clinic 182 scientific publications 31 health professionals $22.9 million in research funding 21 physicians specialized in hypertension cholesterol obesity and diabetes
6 | 2011-2012 IRCM ANNUAL REPORT |7 I N N O V ating CONTRIBUTING 8 core facilities 5 new declarations of invention 3 research platforms 7 new patent filings (or applications) 5 specialized services
8 | 2011-2012 IRCM ANNUAL REPORT |9 Cancer Cholesterol Diabetes Hypertension Cardiovascular diseases Degenerative diseases TRAINING Infectious diseases Neuroethics Clinical research 113 Master’s and PhD students Nervous system 52 postdoctoral fellows Systems biology 58 scholarship holders HIV/AIDS 467 teaching hours Medicinal chemistry Embryonic development
10 | 2011-2012 IRCM ANNUAL REPORT MISSION / THE IRCM AT A GLANCE | 11 To understand the causes of diseases / To find diagnostic tools and means of prevention and treatment / To train a new generation of high-calibre scientists / To contribute to Quebec’s socioeconomic development by facilitating the commercial development of new discoveries MISSION / THE IRCM AT A GLANCE Founded in 1967 Supported by the Fonds de recherche du Québec – Santé (frqs) Independent non-profit institution Member of the Université de Montréal’s ruis Affiliated with the Université de Montréal (Réseau universitaire intégré de santé) Associated with McGill University 425 researchers, students and employees IRCM Clinic affiliated with the Centre hospitalier A budget of 42.3 million dollars de l’Université de Montréal (CHUM) Funded by Quebec ministry of Economic Development, Innovation and Export Trade
12 | 2011-2012 IRCM ANNUAL REPORT | 13 Translational research at the IRCM: precursor to Quebec’s model As early as 1952, the IRCM was born from the idea of bringing together basic and clinical researchers under the same roof. Translational research thus began with the fields of hypertension, atherosclerosis, immune disorders and Parkinson’s disease. After all these years, this model continues to be extremely relevant. The following are two examples of translational research conducted at the IRCM in 2011-2012.
14 | 2011-2012 IRCM ANNUAL REPORT Translational research at the IRCM: precursor to Quebec’s model | 15REPLACING STATINS “We discovered that the PCSK9 enzyme leads IMPROVING THE CLINICAL MANAGEMENT OF THE “Although our society’s ever-growing problems to the deterioration of receptors, located on the TYPE-2 DIABETES EPIDEMIC: A PROJECT AT THE of obesity and sedentary lifestyles are amongSince 1994, statins have been the treatment liver’s surface, that collect bad cholesterol (LDL) HEART OF PERSONALIZED HEALTHCARE the main risk factors for type-2 diabetes, theyof choice to lower cholesterol levels in the particles circulating in the blood and internalize far from justify the occurrence of the disease orblood. Nearly 30 million people are prescribed them in the liver, where they are then disintegrated. Two IRCM teams are currently conducting a the associated cardio-metabolic risk. Resistancestatins today because they suffer from Consequently, PCSK9 leads to an accumulation study that, when completed, could have an impact to insulin, a hormone secreted by the pancreas,familial hypercholesterolemia or have had a of LDL in the blood and contributes to the growth on the management of the type-2 diabetes displayed by peripheral tissues such as muscles,cardiovascular incident such as a stroke. Others of plaque that eventually blocks arteries. Following epidemic. By using proteomics and computational the liver or the adipose tissue, is required for thereceive the drug because, in addition to having numerous observations, we found PCSK9 to be an biology, we will be able to use additional criteria development of the disease. However, the underlyinghigh levels of cholesterol, they are predisposed ideal therapeutic target for the development of a to predict the risk of developing type-2 diabetes, molecular mechanisms to this insulin resistanceto cardiovascular diseases due to various risk new generation of products more effective than the in addition to current criteria such as obesity and remain poorly understood. A better knowledge offactors, including a sedentary lifestyle, smoking currently-available medication. We recently received family history. Hence, we could segment patient these mechanisms will allow us not only to betteror high blood pressure. However, many among a substantial investment from AmorChen that could groups so they could receive the appropriate understand the trigger and the progression of thethem have become intolerant to the drug, to the allow us to develop a novel cholesterol-lowering treatment in due course, according to their risk disease, but also to define therapeutic targets andpoint of having to interrupt treatment. drug. This drug will block PCSK9, which will in turn of developing complications. develop tools for diagnosis and prediction.” significantly lower levels of cholesterol in the blood.”“This intolerance to statins is a catastrophe for “Recent genomic studies have shown that a series RÉMI RABASA-LHORET, MD, PhDpeople suffering from familial hypercholesterolemia. NABIL G. SEIDAH, C.M., O.Q., PhD, MSRC Director, Metabolic Diseases research unit of genes are “susceptible” to insulin resistance. We Director, Biochemical Neuroendocrinology research unit Director, Obesity, Metabolism and Diabetes clinicNew therapeutic approaches are crucial for those developed a process to map protein interaction Director, Research platform on obesity, metabolism and Full IRCM Research Professorwho are intolerant, but also for the large number of Canada Research Chairholder in Precursor Proteolysis networks in human cells. We then applied this diabetespatients for whom the current treatment does not process to the characterization of networks involving Holder of the J.A. DeSève Chair of Excellenceallow them to reach the recommended cholesterol proteins that are coded with the insulin-resistantlevels. Clinical trials are currently underway at susceptibility genes. We are looking for specificthe IRCM in order to evaluate a new therapeutic signatures, named proteomic “imprints”, for each approach, which, once completed, could replace phenotype. These imprints could then be used tostatins and thus provide individuals with a better diagnose or predict the onset of various phenotypestreatment option. These clinical trials were made related to type-2 diabetes.”possible thanks to the discovery of PCSK9 by ourbasic researcher colleague, Nabil G. Seidah.” BENOIT COULOMBE, PhD Director, Gene Transcription and Proteomics research unitROBERT DUFOUR, MD, M.Sc., CSPQ Director, Proteomics discovery platformDirector, Nutrition, Metabolism and Atherosclerosis clinic Director, National platform for human interactome mapping Full IRCM Research Professor
16 | 2011-2012 IRCM ANNUAL REPORT TABLE OF CONTENTS | 17 Message from the Chairwoman of the Board / 18 IRCM Foundation / 100 Message from the President and Scientific Message from the President / 104 Director / 22 Message from the Director / 106 Planning the future / 26 SUPPORTING dISCOVERING / 108 Benefit activities / 30 Research divisions Volunteering TrEATING / 111 IRCM Foundation’s Board of Directors / 112 / 52 Give for Life campaign Board / 113 IRCM Clinic InnovATING GIVING / 116 / 62 TABLE OF CONTENTS Core facilities and technology platforms The impact of your donations / 118 Partners and donors / 120 ContribuTING Research Funds and Chairs / 130 / 70 Technology transfer TRAINING / 74 Tomorrow’s researchers ParticipATING / 84 Science for all Research funding / 90 Administration / 92 IRCM Board of Directors / 93 IRCM Management / 95 Organizational charts / 96 Financial statements / 98
18 | 2011-2012 IRCM ANNUAL REPORT | 19 MESSAGE FROM THE CHAIRWOMAN OF THE BOARD
20 | 2011-2012 IRCM ANNUAL REPORT MESSAGE FROM THE CHAIRWOMAN OF THE BOARD | 21MESSAGE FROM THE CHAIRWOMAN OF THE BOARD A new signature engineer. I also welcome the arrival of Brian Z. I am undertaking my second year as Chair of the Gelfand, Vice President of Institutional relations Board with confidence and enthusiasm, and hopeI proudly accepted to chair the IRCM’s Board of The Board’s Communications Committee expressed and market operations at the Montréal Exchange, that the IRCM’s excellent reputation, and that of itsDirectors. I knew that I was undertaking a demanding a wish to increase the IRCM’s visibility by working who undertakes his first term on the Board in 2012- researchers, continues to spread.mandate. I also knew that the groundwork had been on a signature project to define the IRCM in a few 2013. These news directors join our prestigiouswell laid by my predecessor, Gérard A. Limoges, and words. Following a consultation exercise conducted in team of Board members (see page 93 of this annualthat I would be surrounded by competent individuals collaboration with Dr. Tarik Möröy, his management report).who hold dear the Institut’s success. Working team and the Institut’s communications department,with people I admire, including the President and the Communications Committee submitted aScientific Director, Dr. Tarik Möröy, the researchers proposal that was approved by the Board. Appointment Louise Lambert-Lagacé, C.M., C.Q., Dt. P.and the IRCM’s community, seemed an outstandingproposal to me. Hence, the acronym “IRCM” becomes the designation The Board approved the appointment of Thérèse of use, and the verb “Discovering” the official Leroux as Chair of the IRCM’s ethics committee corporate signature. Discovering is the term that best for research on human subjects. A prominent lawyer,A very busy year describes, in one word, what is done at the IRCM, Thérèse Leroux is a professor in the Faculty of Law because every day, researchers make discoveries in at the Université de Montréal, and a main researcherIn the first months following my appointment, I various fields. The public will also be able to better at the university’s Centre de recherche en droitvisited Avenue des Pins on several occasions to recognize what happens at the Institut without public.familiarize myself with my new role and the people having to decipher the letters of its acronym. ThisI would have the pleasure of working with. A signature also invites people to discover the IRCM.relationship of trust was established, and methods The word “Discovering” will henceforth appear in Acknowledgementsof operation were implemented so that we could all the IRCM’s different communications tools.effectively manage our new tasks. I would like to thank members of the Board of Directors for their hard work and support throughoutThe Board worked on several projects, and more Board recruitments my first year at the helm of the IRCM.particularly on the IRCM’s funding by the Quebecministry of Economic Development, Innovation and Influential members from the Montréal community, I wish to congratulate Dr. Tarik Möröy for theExport Trade and the Fonds de recherche du Québec sitting on the IRCM’s Board of Directors, are remarkable work he accomplishes every year, and for– Santé. This project had a favourable outcome. dedicated to the development, success and future his invaluable and open collaboration. I also thank of our institution. This year, I had the pleasure of everyone at the Institut for their warm welcome. recruiting and welcoming Monique Jérôme-Forget, Special Advisor at Osler, Hoskin & Harcourt and Finally, I would like to acknowledge the departure Korn/Ferry International; Michel Lespérance, of Camille Limoges, and sincerely thank him, on corporate director; and Hélène Robitaille, civil behalf of the entire Board, for his outstanding contributions since 2008 as a Board member.
22 | 2011-2012 IRCM ANNUAL REPORT | 23 MESSAGE FROM THE PrESIDENT AND SCIENTIFIC DIRECTOR
24 | 2011-2012 IRCM ANNUAL REPORT MESSAGE FROM THE PRESIDENT AND SCIENTIFIC DIRECTOR | 25MESSAGE FROM THE PRESIDENT AND SCIENTIFIC Recruitment of researchers the Cardiovascular and Metabolic Diseases research Give for Life fundraising campaignDIRECTOR division. Dr. Berthiaume was previously a researcher I had the honour of welcoming, this year, Benjamin at the Hôtel-Dieu’s CHUM research centre. As The IRCM Foundation’s major fundraising campaignIt is my pleasure to once again present you with a Haibe-Kains as Assistant IRCM Research for Dr. Larochelle, he will continue his work on was publicly launched in fall 2011. Since then, manyreport of this year’s activities at the IRCM, the first Professor and Director of the Bioinformatics and hypertension as IRCM Emeritus Professor, and will significant donations have been confirmed. I wouldyear of my second term of office. Firstly, I would Computational Genomics research unit, which keep consulting with his patients at the clinic. therefore like to thank everyone who contributed tolike to cordially thank the Chairwoman of the is part of the Systems Biology and Medicinal this important campaign. Without their continualBoard of Directors, Louise Lambert-Lagacé, for her Chemistry research division. He also supervises the Finally, it is with great enthusiasm that I announced support and their unwavering commitment, we couldcommitment and her unwavering support. new Bioinformatics core facility. Dr. Haibe-Kains the return of Mathieu Ferron, who completed his not continue to recruit and set up elite researchers holds a PhD in bioinformatics from the Université doctoral studies at the IRCM. He will be Assistant from around the world or offer cutting-edge training Libre de Bruxelles in Belgium and, before his arrival IRCM Research Professor and Director of the new to our students.Sustainable funding at the IRCM, was a postdoctoral fellow at the Dana- Integrative and Molecular Physiology research unit. Farber Cancer Institute at Harvard in Boston. His laboratory will be part of the CardiovascularThe IRCM’s funding is a key issue. Three years ago, and Metabolic Diseases research division. His arrival Congratulationsthe Fonds de recherche du Québec – Santé announced I was also very pleased to announce the hiring of is scheduled for May 2013. He currently worksa complete reform of its funding program for its Cheolho Cheong as Assistant IRCM Research as a research associate in Dr. Gérard Karsenty’s I would like to sincerely congratulate all theaffiliated centres. Despite the IRCM’s excellent Professor. He is Director of the Cellular Physiology laboratory at Columbia University in New York. researchers who won prestigious awards this year,performance, this FRQS reform significantly reduced and Immunology research unit, and has joined the here or abroad. These honours reflect upon thethe Institut’s annual funding. This placed the IRCM Immunity and Viral Infections research division. Institut’s entire community.in a position that could become precarious in the Dr. Cheong obtained a PhD in genetics from the Appointmentlong term. In collaboration with members of the Seoul National University in South Korea. He was Our researchers once again obtained excellentBoard of Directors, we undertook discussions with previously a research associate in the Laboratory of Towards the end of 2011, I suggested to the Board results in different funding agency competitions, atthe Quebec ministry of Economic Development, Cellular Physiology and Immunology at Rockefeller of Directors that Dr. Michel Chrétien, who directed a time when obtaining research grants has becomeInnovation and Export Trade so that the IRCM’s University in New York. the Institut from 1984 to 1994, should be appointed increasingly difficult.operating budget could henceforth be completely IRCM Emeritus Professor. In accordance with thecovered by the ministry. This project was a lengthy In addition, in response to the desire expressed by Dr. Board’s decision, Dr. Chrétien was reinstalled at theone, but came to a positive conclusion in the summer Pierre Larochelle to reduce his professional activities, IRCM in January 2012. He can now continue his Acknowledgementsof 2012. I would therefore like to sincerely thank the position of Executive Director of the clinic and close collaboration with Dr. Nabil G. Seidah and hiseveryone who worked on this crucial matter for the clinical research became available. I therefore had team in the field of cardiovascular diseases. I wish to warmly thank the researchers, students,future of the IRCM, and more particularly, Louise the pleasure of announcing the appointment of employees, and Board members of the IRCM andLambert-Lagacé, Chair of the Board, and Monique Dr. Yves Berthiaume to this position. Renowned the Foundation for their commitment and dedication,Jérôme-Forget, Board member, for their invaluable pulmonologist, Dr. Berthiaume will also set up a and for their contribution to our institution’s success.assistance, and, of course, the ministry for its specialized research clinic in cystic fibrosis at thesupport. IRCM, and will conduct his research projects in the new Cellular and Molecular Lung Biology research unit. He is Full IRCM Research Professor, and joined Tarik Möröy, PhD
26 | 2011-2012 IRCM ANNUAL REPORT | 27 PLANNING THE FUTURE We are continuing to implement the recommendations made in the IRCM’s 2010-2015 strategic plan. Regular communication with members of the Scientific Advisory Board (SAB) occurred throughout the year. Their first scientific and institutional evaluation visit of the IRCM took place in June 2012, and a report is under preparation. The SAB members said to have been delighted by their visit and impressed with the high calibre of the Institut’s researchers, as well as by the cutting-edge technological facilities. Committee members: Roderick R. McInnes, interim Chair (Lady Davis Research Institute, Canada); John Aitchison (Institute for Systems Biology, USA); Peter Bruns (Howard Hughes Medical Institute, USA); Gordon Fishell (New York University, USA); Paul Frenette (Albert Einstein College of Medicine, USA); Walter Rosenthal (Max- Delbrück Center for Molecular Medicine, Germany); Alfred Singer (National Cancer Institute, USA).
28 | 2011-2012 IRCM ANNUAL REPORT | 29Clinical research boost Evaluation of our engineering services and physical plantWe continued our discussions with CHUM in orderto establish extensive collaborations in clinical and An external firm was commissioned to evaluatetranslational research between our two institutions. our engineering services and physical plant.A joint CHUM-IRCM committee was created, and This evaluation is now complete and a report isthis committee made several recommendations currently being studied by the IRCM’s managementthat are currently being assessed. committee.Consolidation of our alliance with the Prioritizing the training of graduate studentsUniversité de Montréal A new graduate studies option in molecular andWe held many meetings with the Université de cellular medicine was established at the IRCM asMontréal and discussed financial support and the part of the Université de Montréal’s programmes depotential revision of our affiliation contract, among biologie moléculaire (molecular biology programs).other topics. These discussions were fruitful and the We should welcome the first students in July 2013.university will continue supporting the IRCM, namely You can learn more about this new program onthrough programs led by the Canada Research page 76 of this annual report.Chairs and Canada Foundation for Innovation, andthrough compensation for student training carriedout at the Institut.Recruitment of researchersWe established a 2012-2014 recruitment planoutlining available positions for new researchprofessors, which was reviewed by members ofthe Scientific Management and Managementcommittees to ensure the scientific development ofall five research divisions.
30 | 2011-2012 IRCM ANNUAL REPORT DISCOVERING | 31 OUR PRIORITIES Conquering cancer / Living with a healthy heart / Fighting infectious diseases / DISCOVERING Understanding embryonic development and the nervous system / Exploring the complexity of biological systems / Participating in ethical debates 5 research divisions 36 research units 182 scientific publications, including 167 peer-reviewed journals 254 researchers and clinicians* * * including postdoctoral fellows and students (as of August 31, 2012)
32 | 2011-2012 IRCM ANNUAL REPORT | 33 2011-2012 7 teams • 2 Canada Research Chairs • 15 publications by the division’s researchers • 1 scholarship holder from the Fonds de recherche du Québec – Santé: Katrina Podsypanina • 2 recipients of the Leaders Opportunity Fund from the Canada Foundation for Innovation: Katrina Podsypanina and William Y. Tsang, for a total funding ot $829,680 (including the contribution from the government of Quebec) • 1 grant from the Cancer Research Society: TarikCONQUERING CANCER Möröy ($120,000) • 1 grant from the Quebec Breast Cancer Foundation: Jean-François Côté (principal investigator) and Jean-Philippe Gratton (co-applicant) ($450,000) • 1 researcher active in the community: Jean-François Côté chaired the Canadian Cancer Society’s Gala des Grands Chefs de Bromont Cancer research division The IRCM actively participates in efforts to cure cancer – the leading cause DID YOU KNOW… of death in Quebec. Cancer research is complex, as more than 100 different types of cancer exist, affecting various organs and systems. ...according to Osteoporosis Canada, as many as two million Canadians suffer from osteoporosis. In Researchers in this field benefit from the extensive knowledge, gained over addition, approximately 25,000 hip fractures occur in Canada every year, and 80 per cent of these 20 years of intense basic and applied research, on the mechanisms and fractures are related to osteoporosis. causes of the malignant transformation of cells. Despite new therapeutic options that allow us to cure a high proportion of cancer, the battle is far from over. At the IRCM, current studies focus on malignant transformation and tumour growth, metastasis, and the genetic bases for predisposition to cancer. Research is also conducted on osteopetrosis, a genetic disease characterized by the absence of bone resorption.
34 | 2011-2012 IRCM ANNUAL REPORT DISCOVERING | 35 NEW RISK FACTOR FOR DEVELOPING OSTEOPOROSIS “My research team and I identified a new gene that modulates bone mass and could become Cancer research division a risk factor for developing osteoporosis. We identified this gene as a novel modulator of bone mineral density in mice and humans. More importantly, we showed that the humanOsteoporosis is a “silent” genetic disease characterized by low bone mineral density and deterioration of gene could represent a new susceptibilitybone tissue, which leads to increased bone fragility and risk of fracture. In all cases, the disease is caused factor for osteoporosis. Hence, this discoveryby an imbalance between the formation and resorption of bone tissue. will help identify individuals with a greater predisposition to the disease who could benefit from preventive measures.” JEAN VACHER, D.Sc.Research unit directors Full IRCM Research Professor Director, Cellular Interactions and Development research unitJean-François Côté, PhD Katrina Podsypanina, MD, PhDDirector, Cytoskeletal Organization and Cell Migration Director, Breast Cancer BiologyAssociate IRCM Research Professor Assistant IRCM Research ProfessorJean-Philippe Gratton, PhD Marie Trudel, PhDDirector, Endothelial Cell Biology Director, Cancer research divisionAssociate IRCM Research Professor Director, Molecular Genetics and DevelopmentCanada Research Chair in Endothelial Cell Functional Full IRCM Research ProfessorSignalling William Y. Tsang, PhDTarik Möröy, PhD Director, Cell Division and Centrosome BiologyDirector, Hematopoiesis and Cancer Assistant IRCM Research ProfessorFull IRCM Research Professor Jean Vacher, D.Sc.Canada Research Chair in Hematopoiesis and Immune Cell Director, Cellular Interactions and DevelopmentDifferentiation Full IRCM Research Professor
36 | 2011-2012 IRCM ANNUAL REPORT | 37 2011-2012 8 teams • 1 Canada Research Chair • 1 IRCM Research Chair • 78 publications by the division’s researchers • 2 scholarship holders from the Fonds de recherche du Québec – Santé: Rémi Rabasa-Lhoret and Jennifer Estall • 1 LIVING WITH New Investigator Award from the Canadian Institutes of Health Research: Jennifer Estall • 6 researchers honoured: Nabil G. Seidah received the 2011 Wilder-Penfield Prix du Québec in biomedical research; May Faraj, visiting scientist, received the 2011 Trophée Femmes arabes in the health category; Michel Chrétien, IRCM Emeritus Professor, was promoted to Officer of the National Order of the Legion of Honour (France); Rémi Rabasa-Lhoret received an award for A HEALTHY teaching excellence in health sciences from the Université de Montréal; Timothy L. Reudelhuber received the Pierre- Bois Excellence Award from the IRCM Foundation; and Claude Lazure was Acting Scientific Director of the Fonds de recherche du Québec – Santé from January to July 2012 • 3 grants from the Canadian Diabetes Association: Jennifer Estall, May Faraj, Rémi Rabasa-Lhoret • 1 « bridge » grant from the Canadian Institutes of Health Research: May Faraj HEART ($100,000) • 1 funding from AmorChem: Nabil G. Seidah ($250,000) Cardiovascular and Metabolic Diseases research division Cardiovascular diseases remain among the leading causes of death in the DID YOU KNOW… western world. At the IRCM, researchers in this division work on the biology of cardiovascular and metabolic diseases. Collectively, their projects lead to a better understanding of these diseases’ risk factors, including genetic …according to the Heart and Stroke Foundation, high blood pressure affects one in five Canadians, factors, hypertension, dyslipidemia, endothelial cell dysfunctions and and is the number one risk factor for strokes. High blood pressure is often referred to as the “silent metabolic disorders. killer” as patients usually do not show any symptoms before complications occur. Research is conducted by both basic and clinical researchers, thereby increasing collaborations and, in turn, reaffirming the clinical relevance of their work.
38 | 2011-2012 IRCM ANNUAL REPORT DISCOVERING | 39 WHAT FACTORS ARE RESPONSIBLE FOR HIGH BLOOD PRESSURE? Cardiovascular and Metabolic “We are studying a hormonal system that acts on blood pressure and are Diseases research division trying to understand the mechanisms responsible for the activity of this system in the body’s various tissues. More precisely, we are interestedBlood pressure is the pressure exerted upon the walls of arteries (blood vessels) when blood circulates in the renin-angiotensin systemthrough the body. Normal blood pressure is defined by a measurement of 120 (systolic pressure) over 80 and the molecular determinants of(diastolic pressure). A person with hypertension (high blood pressure) will consistently show measurements renin’s activity. As a protein that playsof 140 over 90. Beyond these blood pressure values, the risk of complications progressively increases. We a significant role in regulating bloodknow these complications: cerebrovascular disease, heart disease, and chronic kidney disease, to name a pressure, renin is a prime target forfew. But, what are the factors responsible for hypertension? the treatment of hypertension. A better understanding of all these activities combined will certainlyResearch unit directors provide us with the answers we are searching for.”Christian F. Deschepper, MD Timothy L. Reudelhuber, PhDDirector, Cardiovascular and Metabolic Diseases research Director, Molecular Biochemistry of Hypertensiondivision Full IRCM Research Professor TIMOTHY L. REUDELHUBER, PhDDirector, Experimental Cardiovascular Biology Director, Molecular Biochemistry of M. Ram Sairam, PhD Hypertension research unitFull IRCM Research Professor Director, Molecular Endocrinology Full IRCM Research ProfessorJennifer Estall, PhD Full IRCM Research ProfessorDirector, Molecular Mechanisms of Diabetes Nabil G. Seidah, C.M., O.Q., PhD, MSRCAssistant IRCM Research Professor Director, Biochemical NeuroendocrinologyPierre Larochelle, MD, PhD, FRCPC, FACP, FAHA Full IRCM Research ProfessorDirector, Cardiovascular Pharmacology Canada Research Chair in Precursor ProteolysisClaude Lazure, PhDDirector, Neuropeptide Structure and MetabolismFull IRCM Research ProfessorRémi Rabasa-Lhoret, MD, PhDDirector, Metabolic DiseasesJ.A. DeSève Chair of Excellence
40 | 2011-2012 IRCM ANNUAL REPORT | 41 2011-2012 FIGHTING INFECTIOUS 6 teams • 4 Canada Research Chairs • 1 IRCM Research Chair • 17 publications by the division’s researchers • 2 operating grants from the Canadian Institutes of Health Research: Paul Jolicoeur, André Veillette ($968,320) • 1 grant from the Cancer Research Society: Javier DISEASES M. Di Noia ($120,000) • 1 researcher promoted to associate professor-researcher at the Université de Montréal: Javier M. Di Noia Immunity and Viral Infections research division Allergic reactions, respiratory tract diseases and autoimmune diseases are growing problems in our society. The resurgence of infectious diseases thought to have been eradicated and the emergence of new viruses require DID YOU KNOW… ...with over 25 million deaths over the past three decades, HIV is causing one major research efforts in the field of immune system diseases. of the world’s deadliest infectious diseases. According to the World Health Organization, approximately 34 million people were living with HIV/AIDS in This research division groups together scientists interested, on one hand, by 2010. the development of immune cells and the regulation of their functions, and on the other hand, by viral infections, especially those involving viruses that infect immune cells. Collectively, the researchers’ studies lead to a better understanding of immune cell regulation in normal immune responses and during diseases such as autoimmune diseases, viral infections and immunodeficiency.
42 | 2011-2012 IRCM ANNUAL REPORT DISCOVERING | 43 WHY DEVELOP A MOUSE MODEL OF AIDS? “One of my team’s main research projects is the understanding of the HIV-1 virus. To Immunity and Viral achieve this, our laboratory is interested in developing mice models of AIDS. For Infections research division example, to create one of these models, we used a promoter of the CD4 human gene (a receptor of HIV-1) to express the HIV-1 genome in transgenic mice, in the same cellsPaul Jolicoeur has earned degrees in medicine and endocrinology from the Université Laval. He joined that are normally infected in individuals withthe IRCM in 1976. At the time, cloning technologies were not yet discovered and the AIDS virus was not HIV-1. These mice developed many similaryet known. Since then, Dr. Jolicoeur has become a major player in the field of HIV/AIDS by creating phenotypes to those observed in patients withan animal model of the disease in mice. His work represents a significant and vital contribution to the AIDS, such as the loss and activation of CD4international scientific community for the study of this disease. t-cells, thymic atrophy, immunodeficiency, weight loss, abnormal growth, premature death and a kidney disease typical of AIDS.Research unit directors Such models are useful not only to understand the disease, but also to eventually develop aÉric A. Cohen, PhD Paul Jolicoeur, MD, PhD vaccine against HIV-1.”Director, Immunity and Viral Infections research division Director, Molecular BiologyDirector, Human Retrovirology Full IRCM Research Professor PAUL JOLICOEUR, MD, PhDCanada Research Chair in Human Retrovirology Canada Research Chair in Studies of Pathogenesis of Director, Molecular Biology research unit Retrovirus-Induced Diseases Full IRCM Research ProfessorJavier Marcelo Di Noia, PhD Canada Research Chair in Studies of Pathogenesis ofDirector, Mechanisms of Genetic Diversity Woong-Kyung Suh, PhD Retrovirus-Induced DiseasesAssociate IRCM Research Professor Director, Immune RegulationCanada Research Chair in Genetic Diversity Assistant IRCM Research ProfessorHua Gu, PhD André Veillette, MD, MSRCDirector, Molecular Immunology Director, Molecular OncologyFull IRCM Research Professor Full IRCM Research ProfessorAndré-Aisenstadt Chair of Excellence in Immunology Canada Research Chair in Immune System Signalling
UNDERSTANDING44 | 2011-2012 IRCM ANNUAL REPORT | 45 THE NERVOUS 2011-2012 SYSTEM / 7 teams • 1 Canada Research Chair • 23 publications by the division’s researchers PARTICIPATING • 2 honoured researchers: Frédéric Charron received the 2012 Young Investigator Award from the Canadian Association for Neuroscience; Éric Racine was elected a member of the Dana Alliance for Brain Initiatives (DABI) • 1 operating grant from IN ETHICAL the Canadian Institutes of Health Research: Frédéric Charron ($796,365) • 1 grant from the Foundation Fighting Blindness: Michel Cayouette ($295,743) • 1 Canada Research Chair renewal: Marie Kmita • 1 researcher promoted to associate professor-researcher at the Université de Montréal: Éric Racine DEBATES Neurobiology and Development research division Embryonic development is carefully controlled by cellular and molecular mechanisms that ensure the proper functioning of organs in adults. The disruption of these mechanisms often causes diseases, such as cancer, Parkinson’s or Alzheimer’s diseases. DID YOU KNOW… ... the generation of baby boomers, those born between 1946 and 1956, Researchers in this division study the basic mechanisms of development and provide started turning 65 in 2011. It is also known that the prevalence of new considerations for the treatment of neurodegenerative diseases, blindness, muscular neurodegenerative diseases increases with age. We can therefore expect dystrophies and hormone deficiencies. a growing portion of the population to be affected by these pathologies (INSPQ, 2010). In addition, research at the IRCM is conducted in the emerging field of neuroethics. Work in this area is designed to improve our knowledge of the ethical challenges that arise from neurosciences in terms of health care, public information and prevention in neurology, psychiatry and neurosurgery.
46 | 2011-2012 IRCM ANNUAL REPORT DISCOVERING | 47 IS IT POSSIBLE TO RECONNECT DAMAGED AXONS? “The nervous system is not the only system Neurobiology and Development formed during human embryonic development. Blood vessels are also organized into a very research division complex network, which led to the idea that certain molecules could be reused by both the nervous system and the vascular system. We recently discovered that a key moleculeThe brain is made up of billions of neurons organized into a complex network. The inaccurate connection of the vascular system (VEGF) can attractof these neurons has severe consequences on the nervous system’s sensory, motor and cognitive functions. nervous system axons to their targets. MoreTo properly form neural circuits, developing axons (long extensions that form the nerves) need molecules specifically, we identified Flk-1 as the receptorto guide them towards their target. responsible for this effect, making it a prime target for the development of therapies to re-grow axons following lesions of theResearch unit directors central nervous system or neurodegenerative diseases.”Michel Cayouette, PhD Artur Kania, PhD FRÉDÉRIC CHARRON, PhDDirector, Neurobiology and Development research division Director, Neural Circuit Development Director, Molecular Biology of Neural DevelopmentDirector, Cellular Neurobiology Associate IRCM Research Professor research unitAssociate IRCM Research Professor Marie Kmita, PhD Associate IRCM Research ProfessorFrédéric Charron, PhD Director, Genetics and DevelopmentDirector, Molecular Biology of Neural Development Associate IRCM Research ProfessorAssociate IRCM Research Professor Canada Research Chair in Molecular Embryology and GeneticsJacques Drouin, D.Sc., MSRCDirector, Molecular Genetics Éric Racine, PhDFull IRCM Research Professor Director, Neuroethics Associate IRCM Research ProfessorDavid R. Hipfner, PhDDirector, Epithelial Cell BiologyAssociate IRCM Research Professor
48 | 2011-2012 IRCM ANNUAL REPORT | 49 EXPLORING THE 2011-2012 COMPLEXITY 8 teams • 34 publications by the division’s researchers • 1 honoured researcher: Yvan OF BIOLOGICAL Guindon received the 2012 Alfred Bader Award from the Canadian Society for Chemistry and was appointed Knight of the Ordre national du Québec • 1 scholarship holder from the Fonds de recherche du Québec – Santé: François Robert • 1 grant from the National SYSTEMS Institutes of Health: Peter W. Schiller ($1,000,000) • 1 grant from the Cancer Research Society: Jacques Archambault ($120,000) Systems Biology and Medicinal Chemistry research division Systems biology is a rapidly expanding area of research. It examines the immense complexity of biological systems in order to gain a better understanding of the way cells function. The IRCM has seized the opportunity to play a leading role in the DID YOU KNOW… revolution of this emerging discipline. …genomics is the study of a living being’s complete genetic information (DNA). Researchers in this field are working towards mapping human genes The research units working in this division address questions that are central to by using sequencing methods, which will help them understand why, among understanding normal cell functions and their deregulation in diseases, such as other questions, certain people become sick when others remain healthy. cancer and viral infections. The medicinal chemistry component of this division focuses on chemical biology, an area of interdisciplinary research at the crossroads between chemistry and biology. This is where expertise in synthesizing organic molecules is applied to solving problems in cell and molecular biology.
50 | 2011-2012 IRCM ANNUAL REPORT DISCOVERING | 51 A STEP CLOSER TO UNDERSTANDING THE FUNCTION OF GENES “By using modern functional genomics tools, our Systems Biology and Medicinal research team confirmed the first hypothesis that transcription operates in a uniform way Chemistry research division across virtually all genes. As misregulation of transcription often underlies genetic diseases and cancer, this breakthrough provides critical insights that could one day lead to newBy examining a small number of genes, certain pioneering studies that have been long-accepted in the treatments.”field of molecular biology had shown that phosphorylation of RNA polymerase II – one of the mostimportant regulation mechanisms for cells – always occurred in the same prescribed pattern during FRANÇOIS ROBERT, PhDtranscription. However, recent genome-wide analyses challenged this idea by suggesting that this process Director, Systems Biology and Medicinal Chemistry research divisionwas not uniform across different genes. The latter model is very controversial, because it is unclear how, Director, Chromatin and Genomic Expression research unitor why, transcription could work in such radically different ways from one gene to the next. Associate IRCM Research ProfessorResearch unit directorsJacques Archambault, PhD Éric Lécuyer, PhDDirector, Molecular Virology Director, RNA BiologyFull IRCM Research Professor Assistant IRCM Research ProfessorBenoit Coulombe, PhD Marlene Oeffinger, PhDDirector, Gene Transcription and Proteomics Director, Ribonucleoprotein BiochemistryFull IRCM Research Professor Assistant IRCM Research ProfessorYvan Guindon, C.M., PhD, MSRC François Robert, PhDDirector, Bioorganic Chemistry Director, Systems Biology and Medicinal Chemistry researchFull IRCM Research Professor division Director, Chromatin and Genomic ExpressionBenjamin Haibe-Kains, PhD Associate IRCM Research ProfessorDirector, bioinformatics and computational genomicsAssistant IRCM Research Professor Peter W. Schiller, O.Q., PhD, MSRC Director, Chemical Biology and Peptide Research Full IRCM Research Professor
52 | 2011-2012 IRCM ANNUAL REPORT TREATING | 53 IRCM CLINIC A multidisciplinary team Doctors, nutritionists, kinesiologists, nurses T R E AT I N G hypertension – cholestErol – DIABETES AND OBESITY 3 specialized research clinics Hypertension clinic Nutrition, metabolism and atherosclerosis clinic Obesity, metabolism and diabetes clinic
54 | 2011-2012 IRCM ANNUAL REPORT | 55 ACCELERATING The IRCM Clinic boasts three specialized research clinics in the fields of hypertension, cholesterol, CLINICAL and diabetes. Clinical research protocols are regularly conducted, thus contributing to the RESEARCH development of new diagnostic methods, the identification of new biochemical or genetic markers for cardiovascular diseases, and the evaluation of new therapeutic The IRCM’s Outpatient Clinic handles over 16,000 patient visits per year. The approaches. This research IRCM offers its clinical researchers the unique opportunity to follow their patients’ progress on site thanks to its external consultation services. The Institut’s bridges the gap between basic infrastructure and distinctive conceptual model allows for clinical and translational laboratory research and its clinical research, within the framework of an institution devoted to basic research. application in humans. The Institut’s clinic and clinical research are funded directly by the IRCM, and also receive funding from private sources, such as the pharmaceutical industry, government agencies and the Canadian Institutes of Health Research. The IRCM Clinic is affiliated with the Centre hospitalier de l’Université de Montréal.
56 | 2011-2012 IRCM ANNUAL REPORT TReating | 57 The Nutrition, Metabolism and Atherosclerosis Clinic’s research activity The Hypertension clinic assesses and treats patients referred for their high deals with the characterization and treatment of hyperlipidemia, that is to say blood pressure. The research protocols study new diagnostic methods and the increase of cholesterol or other fats in the blood. Experts are studying the treatments for hypertension. Studies are also conducted to better understand nutritional, genetic, biochemical, pharmacological, and molecular components the role of the autonomic nervous system in hypertension and its effects on of these diseases to better understand what causes them and provide the vascular function. appropriate treatment. Nutrition, metabolism and atherosclerosis clinic Hypertension clinic DID YOU KNOW… DID YOU KNOW… ... the liver produces the majority (80 per cent) of the cholesterol used by …according to the Société québécoise d’hypertension artérielle, one in the body for various functions. The other 20 per cent comes from the food five adults in Canada suffers from hypertension. The risk of developing we eat, particularly animal products. hypertension increases with age, in such a way that approximately 50 per cent of men or women aged over 60 have high blood pressure.
58 | 2011-2012 IRCM ANNUAL REPORT TReating | 59 Permanent staff – medical personnel The Obesity, Metabolism and Diabetes clinic allows experts to follow the Directors Nurses Kinesiologists progress of patients suffering from obesity and various metabolic disorders, Robert Dufour Martine Gauthier, head nurse Philippe Briand and, more particularly, patients with type-1 and type-2 diabetes. Patients benefit Pierre Larochelle Lucienne Bourque Corinne Suppere from the support of a multidisciplinary team. Numerous research projects are Rémi Rabasa-Lhoret Maryse Dallaire Joanie Houle Project coordinator ongoing, including the development of an artificial external pancreas and the Nutritionists Hélène Larchevêque Virginie Messier identification of new relationships between hypercholesterolemia and the risk Chantal Blais Jennifer Levasseur Sonia Fortin of developing type-2 diabetes. Annabelle Mathieu Technicians Cherylene Pinaroc Annie Tardif Diane Mignault Obesity, metabolism and diabetes clinic DID YOU KNOW… …according to Diabetes Québec, an estimated 760,000 people in Quebec have diabetes, 200,000 of whom are unaware that they have the disease. The World Health Organization predicts that the number of people with diabetes will double by 2025, making diabetes the new epidemic. Hélène Larchevêque, Lucienne Bourque, Joanie Houle, Martine Gauthier
60 | 2011-2012 IRCM ANNUAL REPORT TReating | 61 What is the nutritionist’s role DID YOU KNOW……as early as the 19th century, a French at the IRCM Clinic?gastronome, Brillat-Savarin, set the table Nutritionists at the IRCM evaluate patients’ eating habits, develop treatmentfor the notion that food has a significantinfluence on the human body’s function- plans adapted to the needs of each person and supervise their effectiveness.ing. In fact, we owe him this famous quote: They also advise patients to help them prevent disease, as well as maintain“Tell me what you eat, and I will tell you or restore their health.what you are.” “For example, the Éducoeur study that we conducted at the IRCM showed thatToday, the increasing variety of foodat our disposal complicates the healthy people at risk of developing cardiovascular diseases could, with a nutritionalchoices consumers should be making. In program tailored to their needs, improve many of the risk factors such asaddition, for adults and children alike, blood pressure, cholesterol, blood sugar and weight. With an evaluation,chronic diseases are on the rise because of practical advice, accompanied visits to the grocery store and tastings ofinadequate lifestyles. lesser-known ingredients, we were able to motivate these individuals with better eating habits and help them correct these risk factors.” CHANTAL BLAIS, Dt.P., BSc Head of the nutrition department, IRCM Clinic
62 | 2011-2012 IRCM ANNUAL REPORT INNOVATING | 63 Core facilities and technology platforms 8 core facilities Animal facilities and animal experimentation | Bioinformatics | Chemical biology | Flow cytometry | Histology | Microscopy and imaging | Molecular biology and functional genomics | Transgenesis and microinjection I N N O VAT I N G 3 ultra-specialized research platforms National platform for human interactome mapping 8 core facilities Proteomics discovery platform 3 research platforms Research platform on obesity, metabolism and diabetes (PROMD) 5 specialized services 5 specialized services Electrophysiology | Molecular modelling | Nuclear magnetic resonance | Protein sequencer | Specialized equipment 50 people serving research
64 | 2011-2012 IRCM ANNUAL REPORT | 65 STRENGTHENING This year, the IRCM set up a Bioinformatics core facility. Supervised by Dr. Benjamin Haibe-Kains, this OUR2011-2012 new facility aims at providing support to scientists, from the IRCM and the TECHNOLOGICAL scientific community, in the analysis of biological and clinical data, and particularly next-generation genomic ADVANTAGE data. With the development of new technologies generating large amounts of biological data, including next-generation sequencing, the To facilitate innovation, the IRCM ensures that it provides its researchers with the complexity of many studies now lies best technologies. The IRCM’s core facilities thereby allow researchers to remain at the forefront of modern science, achieve important scientific breakthroughs, and in the computational analysis of such offer cutting-edge training to tomorrow’s scientists. data. This analysis, which has become Over the years, its core facilities and technology platforms have proven to be impossible to complete “manually”, extremely useful and effective. Certain discoveries may not have been possible now requires the development of without these state-of-the-art resources. algorithms and support from personnel specialized in bioinformatics.
66 | 2011-2012 IRCM ANNUAL REPORT | 67 “Flow cytometry is a specialized technique that has existed for several years and is currently used by many IRCM researchers. Over the years, after numerous technical modifications, the level of sophistication has greatly increased and now allows for more effective sorting and more complex approaches. For example, in my laboratory, we are interested in intracellular organelles, much smaller than cells. We incorporated a fluorescent protein specifically in the organelles we are studying, namely the endocrine secretion granules (pituitary or pancreatic) or the endosomes. We therefore needed to optimize the cytometer’s parameters in order for the device to “see” FLOW CYTOMETRY CORE FACILITY and sort extremely small particles while preserving their structural integrity. This work was complex and required much effort. Today, as a result, we have a brand new method at our disposal that was made DID YOU KNOW… possible thanks to the expertise of the ...flow cytometry is a technique that can analyse individual cells, which offers, among other things, a quick IRCM’s flow cytometry team.” method for researchers to confirm the transfer of a gene using fluorescent markers. CLAUDE LAZURE, Phd The technique consists of streaming cells very quickly, one cell behind the other, through a laser beam. The Director, Neuropeptide Structure and Metabolism research unit device used, the cytometer, can analyze cells individually according to numerous parameters, at the speed Full IRCM Research Professor of several thousand particles per second. The light, reemitted by diffraction and fluorescence, enables the classification and sorting of cells in accordance with several criteria. A computer then calculates the statistical data associated with the measured parameters.
68 | 2011-2012 IRCM ANNUAL REPORT INNOVATING | 69 Research services Executive Director: Louis-Gilles Durand | Assistant Director: Judith Cotton-Montpetit Core facilities Animal experimentation and animal facilities Director: Ion-Ovidiu Jumanca Animal facilities Head: Julie D’amours Animal physiology Head: Manon Laprise Bioinformatics Head: Rashad El-Badrawi | Expert advisor: Benjamin Haibe-Kains Chemical biology Contact person: David Gagnon | Expert advisor: Jacques Archambault Flow Cytometry Head: Éric Massicotte | Contact person: André Veillette Histology Head: Dominique Lauzier Microscopy and imaging Head: Dominic Filion MICROSCOPY AND IMAGING CORE FACILITY Molecular biology and functional genomics Head: Odile Neyret | Expert advisor: François Robert Transgenesis and microinjection Director: Qinzhang Zhu | Supervisor: André Veillette DID YOU KNOW… Technology platforms ...a jellyfish contributed to the explosion of fluorescence in microscopy. The Green Proteomics discovery platform Director: Benoit Coulombe Fluorescent Protein (GFP), a molecule discovered in 1962 and now commonly used in Mass spectrometry and proteomics Head: Denis Faubert microscopy, has existed for over 160 million years in a bioluminescent jellyfish called Research platform on obesity, Aequorea Victoria. Researchers at the IRCM use fluorescent microscopy, a technique metabolism and diabetes (PROMD) Director: Rémi Rabasa-Lhoret | Contact person: Diane Mignault that uses the light emitted by fluorescent molecules to form an image of various National platform for human interactome mapping Director: Benoit Coulombe samples, such as live or fixed cells and tissues. They can thus obtain digital data that would otherwise require many hours of manual data manipulation, including the Other specialized services quantity of cells, the relative fluorescent intensity, surface measures and speed of movement. Electrophysiology Contact persons: Artur Kania, Michel Paquet Molecular modelling Contact persons: Peter W. Schiller, Brian Wilkes Nuclear magnetic resonance Contact persons: Yvan Guindon, Michel Prévost Protein sequencer Contact person: Claude Lazure Specialized equipment Head: Richard Cimon