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RECENT SCIENTIFIC CONTRIBUTIONS DISCOVERING Affiliated with the Université de Montréal
RECENTSCIENTIFICCONTRIBUTIONS
DISCOVERINGAffiliated with the Université de Montréal
IRCM | Scientific contributions 1
TABLE OF CONTENTS IRCM researchers maintain a high performance level in comparison with their peers and contribute to the institute’s reach and influence through their numerous scientific publications. Their research results are published in nationally and internationally renowned scientific journals. This document presents a selection of discoveries that were the subject of public communications. For more information on these breakthroughs, refer to the IRCM website: www.ircm.qc.ca/medias.
CONQUERING CANCER AND GENETIC DISEASES 3 LIVING WITH A HEALTHY HEART AND 5 IMPROVING CARDIOVACULAR FUNCTION FIGHTING INFECTIOUS AND AUTO-IMMUNE DISEASES 6 UNDERSTANDING EMBRYONIC DEVELOPMENT 8 AND THE NERVOUS SYSTEM PREVENTING AND TREATING METABOLIC DISEASES 11 AND ENDOCRINE DISORDERS EXPLORING THE COMPLEXITY OF THE HUMAN GENOME 13 PARTICIPATING IN ETHICAL DEBATES 15 UNDERSTANDING RARE DISEASES 16 OTHER SIGNIFICANT CONTRIBUTIONS 17 IRCM | August 2014 www.ircm.qc.ca
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IRCM | Scientific contributions 3
CONQUERING CANCER AND GENETIC DISEASES 2013 Bioinformatics breakthrough associated with breast and ovarian cancer A bioinformatics expert, in collaboration with researchers in Boston, defined a new method to identify gene sets that predict ovarian and breast cancer prognoses. These results could eventually be applied to other diseases. Benjamin Haibe-Kains | Study published in PLoS Computational Biology | February 2013 “Discovery of the Achilles’ heel for lymphoid leukemia” An international research team found a possible alternative treatment for lymphoid leukemia. The team discovered a molecule that represents the disease’s “Achilles’ heel” and could be targeted to develop a new approach that would reduce the adverse effects of current treatments such as chemotherapy and radiation therapy. Tarik Möröy | Study published in Cancer Cell | February 2013 Reducing the progression of metastases The research team identified the DOCK1 protein as a potential target to reduce the progression of metastases in patients suffering from breast cancer, the most common type of cancer in women. Nearly 90 per cent of cancer patient deaths are attributable to metastasis, thus explaining the importance of understanding the underlying cellular and molecular mechanisms of this harmful process. The study’s results could eventually lead to the development of new drugs that would limit the progression of metastatic breast cancer and could thereby improve patient prognosis. Jean-François Côté | Study published in Proceedings of the National Academy of Sciences (PNAS) | April 2013 Important breakthrough in the fight against breast cancer An IRCM researcher was part of an international team that found an enzyme in triple-negative breast cancer that makes patients less responsive to chemotherapy. This breakthrough opens the door to new treatments for this particularly aggressive type of cancer, which accounts for 15 to 20 per cent of all breast cancers and is associated with a poor prognosis. Benjamin Haibe-Kains | Study published in Proceedings of the National Academy of Sciences (PNAS) | June 2013 2011 Identification of a new gene that modulates bone mass and that could become a risk factor for developing osteoporosis. This discovery could help identify individuals predisposed to developing the disease. Jean Vacher | Study published in Cell Metabolism | October 2011 2010 Discovery that a variant of the Growth Factor Independence 1 (GFI1) gene predisposes humans to develop acute myeloid leukemia (AML), a certain subtype of blood cancer. This variant could be used in the future as a new biomarker for evaluating prognosis in AML patients. Tarik Möröy | Study published in Blood | January 2010 Identification of a new intracellular mechanism responsible for modulating vascular permeability: the nitrosylation of the beta-catenin protein by nitric oxide. This scientific breakthrough could have an impact on the treatment of cancerous tumours by altering the permeability of the blood vessels irrigating them. Jean-Philippe Gratton | Study published in Molecular Cell | August 2010 Identification of a protein called Gfi1b that can regulate certain characteristics of blood stem cells, which could lead to a better treatment for leukemia patients. Tarik Möröy | Study published in Blood | September 2010 Discovery of a novel molecular mechanism in the control of cell motility, which could eventually lead to the development of new cancer-treating drugs that could block the spread of tumours (metastasis). Jean-François Côté | Study published in Current Biology | October 2010 Identification of a mechanism regulating activation-induced deaminase (AID), a B-lymphocyte enzyme that creates deliberate mutations in the DNA encoding antibodies, which helps produce an appropriate immune response. This breakthrough could be important for the therapy of some types of lymphoma and leukemia. Javier M. Di Noia | Study published in The Journal of Experimental Medicine | November 2010
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Identification of a new regulator playing a critical role in the development of B cells, which produce antibodies. This study could lead to a new target for therapeutic interventions in the treatment of certain types of blood cancer. Tarik Möröy | Study published in Immunity | December 2010
2009 Discovery of the key role played by a family of three small molecules essential to the eradication of cancerous cells. This finding is important in order to understand how the immune system can eliminate blood cancers, such as leukemia and lymphoma, as well as cells infected by viruses such as the Epstein-Barr virus (which leads to infectious mononucleosis) and HIV (which causes AIDS). André Veillette | Study published in Nature Immunology | August 2009 Demonstration that a change in endothelial cell permeability in arteries is due, in part, to the enzyme eNOS. In removing the characteristic high permeability of blood vessels within tumours, the inhibition of the enzyme eNOS through this new mechanism could slow down their development, which could have therapeutic implications for oncology, among others. Jean-Philippe Gratton | Study published in Blood | October 2009 2004 Discovery of a new role of the GATA-4 protein in decreasing chemotherapy’s harmful effects on the heart. This finding will allow for the optimal use of anti-cancer agents, and will also pave the way for new protective therapies for the heart. Mona Nemer | Study published in Proceedings of the National Academy of Sciences (PNAS) | April 2004 Identification of the genes that control the anti-cancer immune response. This discovery will lead to the creation of drugs able to stimulate the immune response against several types of cancer. André Veillette | Study published in Immunity | November 2004 2003 Identification of a gene responsible for a type of hereditary osteoporosis. This discovery will lead to better detection, prevention and treatment of bone diseases such as osteoporosis. Jean Vacher | Study published in Nature Medicine | April 2003 Discovery of cavtratin’s unexpected effect of slowing down the development of tumours by reducing the permeability of the blood vessels that irrigate them. This discovery offers new therapeutic options for certain types of cancer by inhibiting the synthesis of nitric oxide. Jean-Philippe Gratton | Study published in Cancer Cell | July 2003
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LIVING WITH A HEALTHY HEART AND IMPROVING CARDIOVASCULAR FUNCTION 2011 Several publications on five of nine PCSK enzymes. These discoveries could have several positive health impacts, including those on cholesterol, osteoporosis and cancer. Nabil G. Seidah | Study published in The Journal of Biological Chemistry / Atherosclerosis, Thrombosis, and Vascular Biology | February 2011 2009 Discovery of an intracellular pathway important in the control of bad cholesterol, which could have a great impact on the treatment of hypercholesterolemia and coronary artery diseases. Nabil G. Seidah | Study published in The Journal of Biological Chemistry | October 2009 2008 Demonstration in which the administration of sildenafil (Viagra) protects the heart in mice with Duchenne muscular dystrophy. The discovery suggests a new way of treating cardiac complications in patients suffering from this disease. Christian F. Deschepper | Study published in Proceedings of the National Academy of Sciences (PNAS) | May 2008 A discovery on the control of bad cholesterol, which paves the way toward the development of a new drug that would lower blood cholesterol to recommended levels. A drug that would block PCSK9 could either be used alone or in combination with statins, and would be highly beneficial for patients on whom statins do not work or who are unable to take this drug. Nabil G. Seidah | Study published in The Journal of Biological Chemistry | November 2008 2005 Discovery of the benefits of phystoestrogen in the prevention of cardiac hypertrophy. This finding implies that infants, whose mothers’ diets were rich in soya, have fewer risks of suffering from congestive heart failure. Christian F. Deschepper | Study published in American Journal of Physiology | May 2005 2003 Discovery of a link between the NARC-1 gene and a form of familial hypercholesterolemia. This discovery will result in better prevention, thanks to a more accurate diagnosis based on the disease’s genetic causes. Nabil G. Seidah | Study published in Nature Genetics | May 2003
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FIGHTING INFECTIOUS AND AUTO-IMMUNE DISEASES 2014 A new function for an important player in the immune response The team of researchers uncovered a new function of AID, a crucial enzyme for the immune response. This breakthrough could help explain a rare genetic disorder, hyper-IgM syndrome type 2 (HIGM2), which dramatically compromises the immune’s system ability to fight infectious diseases, causing an immunodeficiency syndrome. Javier M. Di Noia | Study published in Proceedings of the National Academy of Sciences | March 2014 How does our immune system kill abnormal blood cells? Researchers explained how our immune system kills abnormal blood cells in order to protect us against viruses and cancer cells. Their discovery could lead to new treatment avenues for leukemia, lymphoma and certain types of infectious viral diseases. André Veillette | Study published in Journal of Experimental Medicine | April 2014 2013 A novel research model for the study of auto-immune diseases The scientists were the first to find a way to separate two important mechanisms that improve the quality of antibodies, the proteins used by the immune system to identify and neutralize foreign objects like bacteria and viruses. They thereby discovered a novel model to the study certain auto-immune diseases such as lupus or rheumatoid arthritis, or some infections like influenza. Javier M. Di Noia | Study published in The Journal of Immunology | June 2013 2012 Explanation of a poorly understood molecular mechanism associated with a human immune disorder known as XLP disease or Duncan’s syndrome. This breakthrough on the function of the SAP molecule could have implications on the role of the same molecule in other diseases such as lupus and arthritis. André Veillette | Study published in Immunity | June 2012 2010 Discovery of a new mechanism through which HIV-1 manipulates natural immunity. This scientific breakthrough could open new avenues for therapeutic intervention against the human immunodeficiency virus (HIV-1). Éric A. Cohen | Study published in Blood | February 2010 Explanation of the negative role played by the Vpu viral protein on the expression of Tetherin, which contributes to the emergence of HIV-1 in humans. This discovery could eventually lead to the development of new strategies to combat AIDS. Éric A. Cohen | Study published in PLoS Pathogens | March 2010 Discovery of the function of the PTP-PEST protein located in T cells, which may open new avenues in the treatment of multiple sclerosis and other autoimmune diseases. André Veillette | Study published in Immunity | August 2010 Discovery of the involvement of the viral protein R (Vpr) in HIV infection and AIDS by blocking normal cell division. This new information will allow the scientific community to better focus its efforts, and will eventually lead to a better understanding of HIV infection and AIDS pathogenesis. Éric A. Cohen | Study published in PLoS Pathogens | September 2010 2009 Identification of one of the basic mechanisms controlling NK (“natural killer”) cell activity, produced by the immune system and responsible for eliminating cancerous cells and cells infected by viruses such as lymphoma. This discovery could have a significant impact on the treatment of cancers and infectious diseases. André Veillette | Study published in Nature Immunology | January 2009 Identification of new mechanisms regulating an enzyme (AID) essential for the antibody-mediated immune response. A better understanding of these mechanisms could help clarify the cause of certain genetic immunodeficiencies. Javier M. Di Noia | Study published in Nature Structural & Molecular Biology | May 2009
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Identification of a crucial signal transduction mechanism that promotes the production of the key immunological weapon: antibodies. Woong-Kyung Suh | Study published in Proceedings of the National Academy of Sciences (PNAS) | November 2009 2008 Explanation of a new mechanism regulating type I interferon production in while blood cells. This discovery could eventually help physicians develop better therapeutic strategies to fight infectious diseases. Andrew P. Makrigiannis | Study published in Journal of Experimental Medicine | December 2008 2007 Identification of a new cellular protein complex targeted by the HIV-1 Vpr protein to stop the division of infected cells. The major breakthrough could lead to the development of a new class of drugs to combat HIV. Éric A. Cohen | Study published in PLoS Pathogens | July 2007 2006 Identification of immune cell defects that give rise to a fungal infection commonly related to HIV. These findings will help in the development of better treatments to prevent such opportunistic infections in HIV patients. Paul Jolicoeur | Study published in The Journal of Immunology | July 2006 2005 Identification of the molecule known as EAT-2, which is present in NK (natural killer) cells and suppresses their killer, yet essential, functions. This major breakthrough will help improve the effectiveness of treatments against cancer and infectious diseases, such as hepatitis and herpes. André Veillette | Study published in Nature Immunology | August 2005 2004 Identification of one of the basic mechanisms that control the production of antibodies by immune-system cells, known as B lymphocytes or B cells. This discovery could revolutionize the treatment of autoimmune diseases, such as juvenile diabetes, lupus and rheumatoid arthritis. André Veillette | Study published in Immunity | November 2004
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UNDERSTANDING EMBRYONIC DEVELOPMENT AND THE NERVOUS SYSTEM 2014 Discovery of a “conductor” in muscle development The team of researchers identified the receptor BA13 as the “conductor” in the fusion of muscle cells, a critical step in the formation of muscle tissue during embryonic development. Given the potential applications on the regeneration of tissue from stem cells, this discovery could have an important impact on the treatment of muscular diseases such as myopathies and muscular dystrophies. Jean-François Côté | Study published in Proceedings of the National Academy of Sciences (PNAS) | February 2014 How are damaged cells eliminated in developing embryos? The study reveals new details about a quality-control mechanism that operates during embryonic development. This discovery shed new light on how organisms deal with genomic stress, which predisposes individuals to a range of diseases, including cancer. Éric Lécuyer | Study published in Developmental Cell | May 2014 2013 A scientific breakthrough that contributes to a better understanding of embryogenesis A research team analyzed the impact of Hox genes on the control of organ and tissue growth during embryonic development. The study confirms that this family of genes does in fact control limb bud growth by regulating the signalling of a specific growth factor (FGF). This discovery opens new avenues to better understand how growth processes are regulated during embryogenesis. Marie Kmita | Study published in Development | May 2013 A breakthrough helps further out understanding of such disorders as autism and schizophrenia Researchers analyzed specialized areas of cells known as adhesion complexes that enable cells to interact and bind with one another or with extracellular components. The team’s research focuses on the synapse, which is a structure that enables a neuron to pass a signal to another cell, making it essential for the proper functioning of the nervous system. The new concepts proposed by the study will accelerate future studies on synapse development and plasticity, and contribute to furthering our understanding of certain neuropsychiatric disorders such as autism and schizophrenia. Hideto Takahashi | Study published in Trends in Neurosciences | July 2013 Identification of new proteins crucial for hearing A team of researchers identified a group of proteins crucial for shaping the cellular organ responsible for detecting sounds. Research has shown that mutations in one of the studied proteins are associated with inherited forms of hearing loss in humans. By defining the function of this class of proteins in targeted cells, the researchers’ work helps explain the mechanisms that could cause hearing loss. Michel Cayouette | Study published in Developmental Cell | October 2013 Discovery of a protein’s critical role in the brain The researchers discovered that the protein PC7 plays a critical role in the brain by affecting certain types of cognitive functions such as anxiety, learning and emotional memory. Their results could have a significant impact on regulating behaviour related to anxiety disorders and trauma. Results of a second study demonstrate that a lack of PC7 also results in an excess of dopamine in the brain. Collectively, these discoveries could be very significant for a number of conditions related to anxiety and trauma, such as bipolar disorder and posttraumatic stress disorder. Nabil G. Seidah | Studies published in Nature and Proceedings of the National Academy of Sciences (PNAS) | December 2012 and October 2013 Important discovery for the diagnosis of genetic diseases Researchers have shown the importance of the DNA architecture in controlling the activity of genes, especially those required for proper embryonic development. Their discovery paves the way for studying the mechanisms that control the architecture of chromatin, which should have a significant impact on identifying the causes and diagnosing genetic diseases. Marie Kmita | Study published in PLoS Genetics | December 2013
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2012 Important breakthrough in the fight against muscular dystrophies. This international collaboration could lead to a better understanding of myotonic dystrophy (Steinert’s disease), the most common form of muscular dystrophies seen in adults, and to the development of diagnostic tools for monitoring disease progression and response to therapy. Éric Lécuyer | Study published in Cell | September 2012 Discovery of a nerve cell’s internal clock, used during embryonic development. This breakthrough could lead to the development of new tools to repair and regenerate nerve cells following injuries to the central nervous system. Frédéric Charron | Study published in Neuron | November 2012 Identification of a new mechanism that allows retinal stem cells to give rise to two different neuronal cell types when they divide. This breakthrough provides an essential first step towards using stem cells to replace damaged photoreceptors. Michel Cayouette | Study published in The Journal of Neuroscience | November 2012 First study showing that the mechanism generating our fingers and toes is similar to the theoretical model for pattern formation known as the Turing mechanism. These findings further support the key role of Hox genes in the transition of fins to limbs during evolution, one of the most important anatomical innovations associated with the transition from aquatic to terrestrial life. Marie Kmita | Study published in Science | December 2012 2011 Discovery of the mechanism of action required for the proper functioning of the Sonic Hedgehog protein, which gives cells the information needed for the embryo to develop properly. This breakthrough could also lead to new avenues for the treatment of certain diseases such as cancer. Frédéric Charron | Study published in Neuron | June 2011 First demonstration that a key molecule of the vascular system guides axons during the formation of neural circuits. This connection between the nervous system and the vascular system could be a good starting point for the development of therapies for neurodegenerative diseases. Frédéric Charron | Study published in Developmental Cell | June 2011 Discovery of a new piece of the puzzle in the development of our nervous system and, more specifically, in motor neuron axons growing in limb muscles. This elucidation of motor system mechanisms will offer the scientific community a new basis for understanding neural development. Artur Kania | Study published in Neuron | July 2011 2010 Discovery of a new molecular mechanism that guides visual nerves towards the brain, which sheds light on the molecular mechanisms involved in the formation of the visual system. Frédéric Charron | Study published in The Journal of Neuroscience | January 2010 Findings show that using specific inhibitors of ACAT1’s expression and activity could be a new and extremely interesting therapeutic option to treat Alzheimer’s disease. Nabil G. Seidah | Study published in PNAS | January 2010 Identification of computers and microscopes capable of predicting the future of neural progenitor cells before they actually divide. The study suggests that new genes regulating stem cell biology could be found by this approach. Michel Cayouette | Study published in Nature Methods | February 2010 Discovery that the mutation found to cause mirror movements is located in a gene called DCC (Deleted in Colorectal Carcinoma). The first to shed light on the role of the DCC gene in the formation of brain cell connections in human, this discovery is important to provide new understanding of the genetic cause of mirror movements and to improve scientific knowledge of the brain’s functioning. Frédéric Charron | Study published in Science | April 2010 Explanation of the link between the development of axons and cell body positions of spinal motor neurons. This important breakthrough suggests one of the first molecular models addressing the emergence of organization in the nervous system. Artur Kania | Study published in PLoS Biology | August 2010
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2009 Demonstration that Src family kinases (SFKs) are essential for motor axon guidance in limb development. Understanding how such nerve guidance signals work could have very important implications for the regeneration of nerve connections in the damaged or degenerating nervous system. Artur Kania | Study published in The Journal of Neuroscience | April 2009 Identification of a key molecular pathway required for the formation of the brain’s neural circuit. This discovery could help treat spinal cord injuries and neurodegenerative diseases. Frédéric Charron | Study published in Neuron | May 2009
2008 Development of a new tool for targeted cell ablation. The technique is of broad interest to the scientific community and will be useful for addressing issues related to cell interaction, organogenesis, tissue homeostasis and regeneration. Marie Kmita | Study published in PNAS | September 2008 Demonstration of the precise role played by Dock1 and Dock5 genes in muscle tissue formation. These genes are critical regulators of the fusion process during myogenesis in mammals. Jean-François Côté | Study published in PNAS Early Edition | September 2008 Discovery of a new mechanism that regulates neural stem cell development. These findings could influence the development of future cell replacement therapies. Michel Cayouette | Study published in Neuron | October 2008 Demonstration showing how a family of proteins present in the developing limb controls nerve targeting from the spinal cord to the muscles of the limb. A better understanding of the process of limb nerve development will contribute to the development of new strategies for treating patients with a diseased or damaged nervous system. Artur Kania | Study published in Neuron | December 2008
2006 Discovery of a molecular mechanism underlying limb architecture and asymmetry (the fact that our fingers are not identical). This is an important finding as the asymmetry of a limb is essential to its wide range of motion. Marie Kmita | Study published in Nature | October 2006 New understanding of the formation mechanism for myelin, the nerve component affected in multiple sclerosis and peripheral neuropathies. This discovery could have a major impact on the treatment of such diseases, as well as an important influence on myelin reconstruction strategies. Michel Cayouette | Study published in Science | November 2006 Identification of a key gene required for brain neural circuit formation. This discovery could lead to new strategies for treating brain and spinal cord injuries, as well as neurodegenerative diseases such as Alzheimer’s and Parkison’s diseases. Frédéric Charron | Study published in Nature | November 2006 2003 Development of an experimental model of Parkinson’s disease. This breakthrough advances the understanding and prevention of the disease, and opens new avenues for its treatment. Jacques Drouin | Study published in Development | June 2003
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PREVENTING AND TREATING METABOLIC AND ENDOCRINE DISEASES 2014 A new early predictor of increased diabetes risk A research team discovered that the PGC-1α protein found in muscle tissue may contribute to the development of type 2 diabetes later in life. The study showed that, over time, the absence of this protein in the muscle increases inflammation in the liver and adipose tissue (fat). The study’s results indicate that the protein could be a promising early predictor of increased diabetes risk and that drugs to increase the levels of this protein may help prevent or delay the progression of the disease. Jennifer Estall | published in American Journal of Physiology – Endocrinology and Metabolism | January 2014 A link found between pollutants and certain complications of obesity In collaboration with a team in Norway, researchers found a link between persistent organic pollutants (POPs) and certain metabolic complications of obesity. This breakthrough could eventually help improve the prevention, diagnosis and treatment of cardiometabolic risk associated with obesity, such as diabetes, hypertension and cardiovascular disease. Rémi Rabasa-Lhoret | Study published in The Journal of Clinical Endocrinology & Metabolism | February 2014 2013 Artificial pancreas: the way of the future for treating type 1 diabetes Researchers were the first to conduct a trial comparing a dual-hormone artificial pancreas with conventional diabetes treatment using an insulin pump, which showed improved glucose levels and lower risks of hypoglycemia. The scientists found that the artificial pancreas improved glucose control by 15 per cent and significantly reduced the risk of hypoglycemia as compared with conventional treatment using an insulin pump. This study represents an important step in the development of an external artificial pancreas, which could substantially improve the management of diabetes and reduce daily frustrations for patients. Rémi Rabasa-Lhoret | Study published in the Canadian Medical Association Journal | January 2013 New mechanism to prevent type 2 diabetes in obese individuals A study demonstrated that the number of LDL particles carrying bad cholesterol in the blood is an important factor in promoting the risk for type 2 diabetes in obese individuals. This discovery may help identify people with a higher risk of developing type 2 diabetes and cardiovascular disease and target them with pharmaceutical or dietary interventions to prevent the onset of these diseases. May Faraj | Study published in the Journal of Lipid Research | May 2013 2012 Reprogramming the identity of certain cells in the pituitary gland led to the identification of new cell mechanisms. This discovery could eventually lead to new pharmacological targets for the treatment of Cushing’s disease. Jacques Drouin | Study published in Genes & Development | October 2012 2011 Unexpected discovery on hormone secretion and the organization of pituitary cells into structured networks. Disturbances in the two studied networks (cells that modulate our responses to stress and cells that control reproduction) could be associated with hormone deficiencies. Jacques Drouin | Study published in Proceedings of the National Academy of Sciences (PNAS) | July 2011 2009 First 3-D modeling of a critical component of an insulin-activating enzyme. This three-dimensional picture opens the door to a better understanding of the granule-sorting mechanism and may lead to new insights into endocrine disorders, such as obesity-related diabetes. Timothy L. Reudelhuber | Study published in PNAS | May 2009
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2006 Discovery of the mechanism of hormone resistance in pituitary tumours, which cause Cushing disease. This insight will allow for the rational design of therapeutic approaches, which, in turn, will lead to more efficient support for Cushing disease patients. Jacques Drouin | Study published in Genes and Development | October 2006 2003 Identification of the cause of a fatal hormone deficiency in infants. The new discovery provides an explanation for some infant deaths – a deficiency in a hormone that controls glycemia. Jacques Drouin | Study published in Genes & Development | March 2003
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EXPLORING THE COMPLEXITY OF THE HUMAN GENOME 2014 An important controversy in molecular biology The research team tackled an important controversy on the function of Mediator, a transcription co-activator. The debate within the scientific community is mainly focused on where Mediator exerts its function. To address this issue, the researchers performed a thorough genomic study and showed, for the first time, the different steps involving Mediator in living cells. François Robert | Study published in Nature Structural & Molecular Biology | April 2014 2013 Predicting response to therapeutic drugs A team constructed predictive models for 16 drugs on cell lines and demonstrated that they are difficult to validate based on independent data. This breakthrough is important for the bioinformatics and biomedical communities who often rely on this type of data to characterize and predict response to therapeutic drugs. Benjamin Haibe-Kains | Study published in Journal of the American Medical Informatics Association (JAMIA) | February 2013 A new code in biology offers hope for the treatment of degenerative diseases A team of scientists proposed the existence of a new code in biology. While the genetic code specifies how DNA makes proteins, the researchers suggested that the “chaperone code” stipulates how proteins produce a functional proteome. The existence of this new chaperon code is redirecting research efforts and creating new hopes for the treatment of degenerative diseases. Benoit Coulombe | Studies published in PLoS Genetics and Biochimica Biophysica Acta | January and May 2013
The importance of standardizing drug screening studies A bioinformatics expert examined inconsistencies between two large-scale pharmacogenomic studies. The study supports the need for further development and standardization to improve the reproducibility of drug screening studies, as they are important in identifying new therapeutic agents and their potential combinations with existing drugs. The researcher stresses that this study and the resulting observations could not have been possible if the data had not been well documented and made accessible to the scientific community. This represents a big success for open data science and reproducible research. Benjamin Haibe-Kains | Study published in Nature | December 2013 2012 Confirmation that the phosphorylation of RNA polymerase II, a key enzyme in the process of gene expression, is uniform across all genes. This discovery, which contributes to numerous debates on the topic, represents a major contribution to the scientific community in the understanding of different cellular processes within the field of molecular biology. François Robert | Study published in Molecular Cell | January 2012 Definition of the interaction between two essential proteins that control inflammation: the transcription factors Stat3 and the glucocorticoid receptor (GR). This important breakthrough will contribute to a better understanding of the human genome. Jacques Drouin | Study published in Molecular Cell | July 2012 2010 Mapping of all the fragile sites of the yeast Saccharomyces cerevisiae’s genome. The method used can be applied to humans. François Robert | Study published in Nature Structural and Molecular Biology | February 2010 Discovery that RNA polymerase II erases its own tracks after passing through nucleosomes, which is part of an important process to avoid complications due to cryptic gene expression. François Robert | Study published in PLoS Genetics | November 2010
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2009 Discovery of a new perspective on the role of histone variants of RNA polymerase, which have the function of “cleaning” the genome of the histone variants incorporated in the wrong areas. François Robert | Study published in PLoS Genetics | October 2009 2007 Development of a new proteomics approach, which promises to have a profound impact on our current understanding of the human proteome and the function of its individual proteins. Benoit Coulombe | Study published in Molecular Cell | July 2007 2006 Mapping of "gene switches" within the human genome. This discovery may revolutionize the way we think about gene regulation and speed up discovery for diagnostics and treatments. François Robert | Study published in Genome Research | April 2006
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PARTICIPATING IN ETHICAL DEBATES 2014 Helping young adults with neurodevelopmental disabilities The team of neuroethics experts addressed shortcomings in transitional care in the Canadian healthcare system. They identified important challenges in the transition from paediatric to adult health care, especially among young adults with neurodevelopmental disabilities (such as autism spectrum disorder, fetal alcohol spectrum disorders and cerebral palsy). Eric Racine | Article published in Paediatrics & Child Health | February 2014 What is being said in the media and academic literature about neurostimulation? Ethics experts raise important questions about neurostimulation techniques such as transcranial direct current stimulation (tDCS), which have gradually gained favour in the public eye over the past several decades. Their report analyzed the rising tide of tDCS media coverage while regulatory action is lacking and ethical issues need to be addressed. Eric Racine | Article published in Neuron | May 2014 2013 Ethical issues in research on cognitive enhancers for healthy individuals The research team published an article that analyzes and characterizes, from an ethics standpoint, the different positions towards research on cognitive enhancement, a term that usually refers to drugs used to augment cognitive performance or alter mood and behaviour. This article could bring greater awareness of the choices available to the scientific community and emphasize the need for an international discussion about the direction of cognitive-enhancement research. Eric Racine | Article published in EMBO reports, Science & Society section | March 2013 2012 Publication of a book, Vegetative State: A Paradigmatic Problem of Modern Societies: Medical, ethical legal, and social perspectives on chronic disorders of consciousness, with colleagues from the University of Munich, Ralf Jox, Katja Kuehlmeyer et Georg Marckmann. This book is based on an international workshop during which experts in the fields of medical ethics, neuroethics and neuroscience were invited to share their perspective on decision-making for patients in the vegetative state. Eric Racine | Book published by LIT Verlag | April 2012 Analysis of the clinical, ethical and social issues relating to disorders of consciousness, considering the growing number of requests clinicians receive from patients’ families who wish to use novel techniques for the diagnosis, prognosis and treatment of chronic disorders of consciousness such as the vegetative state. Eric Racine | Report published in The Lancet Neurology | August 2012 Report on the role of physicians in the prescription of cognitive enhancers to healthy individuals, in view of the increasing use by students on university campuses of prescription stimulants to enhance mental performance. Recommendations are based on the professional integrity of physicians, the drugs’ uncertain benefits and harms, and limited healthcare resources. Eric Racine | Report published in Journal de l’Association médicale canadienne | December 2012 2010 Publication of a monograph, Pragmatic Neuroethics: Improving Treatment and Understanding of the Mind-Brain, which argues that the emerging field of neuroethics offers a way to integrate certain specialties (neurology, psychiatry, neurosurgery) with humanities and social sciences in order to tackle key ethical challenges and improve patient care. Eric Racine | Monograph published by MIT Press | June 2010 2008 Review of the Schiavo case’s media coverage, which provides an objective measure of misinformation and underlines the limitations of information made available to the media. The study comes to the conclusion that specialists must adopt strategies to improve the quality of information relayed to the public. Ethical and medical debates would certainly benefit from information that is both more accurate and more accessible. Eric Racine | Report published in Neurology | September 2008
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UNDERSTANDING RARE DISEASES 2013 Characterization of a molecule involved in certain rare diseases The researchers characterized a novel protein known as NPHP5, which is involved in certain rare diseases such as Leber congenital amaurosis (an inherited eye disease characterized by severe loss of vision) and Senior-Løken syndrome (an inherited disorder associated with retinal and renal failure). With their study, they uncovered the functional significance of the NPHP5 protein, and were able to define its location as well as its interactions with other important proteins. This information could lead to the development of novel pharmacological approaches to treat NPHP5 deficiency in patients with such diseases. William Y. Tsang | Study published in Human Molecular Genetics | April 2013
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OTHER SIGNIFICANT CONTRIBUTIONS Identification of a new function of the E2A transcription factor as a restrictor of lymphocyte proliferation. Identification of the gene (Tpit) responsible for a lethal hormonal deficiency in children. Development of an animal model of AIDS, which demonstrates that HIV viral proteins can, on their own, inhibit immune system functions. Identification of the mechanism of action of a deadly mononucleosis syndrome and of the development of malignant tumours in young boys. Identification of new therapeutic targets to regularize blood pressure in pregnant women without harming the foetus. Identification of a cardiac hormone, ANF, essential for regulating blood pressure. Discovery of the genetic foundation of certain cancers and immune deficiencies. Discovery of a gene related to familial hypercholesterolemia. Discovery of new properties of an antihypertensive treatment by way of a conversion-enzyme blocker. Characterization of genes essential to foetus development. Development of an analgesic 3,000 times more powerful than morphine. Development of a muscular re-adaptation device for hands, as well as an electronic stethoscope. Development of selective and effective methods for the synthesis of complex molecules. These new chemical tools allow access to a new category of antibiotics, as well as anticancer and anti-inflammatory drugs, which were previously difficult to acquire. Discovery and synthesis of the first antioxidant peptide that specifically targets cells’ mitochondria, which represents a new class of potential drugs.
