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Aleixo Muise

Title:
Senior Scientist, Cell Biology
Designations:
MD, PhD, FRCPC
Email:
aleixo.muise@sickkids.ca
Alternate Contact Name:
Karoline Fiedler
Alternate Phone:
416-813-6858
Alternate Email:
karoline.fiedler@sickkids.ca
U of T Positions:
Professor, Departments of Paediatrics and Biochemistry and the Institute of Medical Sciences
Chair Positions:
Canada Research Chair (Tier 1) in Paediatric Inflammatory Bowel Disease

Hospital Positions

Staff Gastroenterologist
Division of Gastroenterology, Hepatology and Nutrition 

Co-Director
Inflammatory Bowel Disease (IBD) Centre

Websites

Biography

Dr. Aleixo Muise is a leader in the development of precision medicine to treat children diagnosed under six years of age with very early onset inflammatory bowel disease (VEOIBD) and intestinal diseases.

He received his education through St. Francis Xavier University (B.Sc.), Carleton University (M.Sc.), and Dalhousie University (PhD in Biochemistry). Muise then completed his MD at the University of Toronto, with a Paediatric Residency at The Hospital for Sick Children (SickKids) and a Subspecialty Fellowship in the Division of Gastroenterology, Hepatology and Nutrition. He finished Postdoctoral training in the laboratory of Dr. Daniela Rotin.

Muise established the world’s first multidisciplinary clinic focused exclusively on VEOIBD at SickKids. He developed the interNational Early Onset Pediatric IBD Cohort Study (NEOPICS), as well as co-founded and co-directs the international VEOIBD Consortium and the PEDIatric COngenital Diarrhea and Enteropathy Consortia study (PEDICODE). Dr. Muise also hosts an international training program for postdoctoral fellows (MD and PhD). These fellows visit his clinic and lab to study novel and known genes in IBD patients.

Research

Dr. Muise’s research lab conducts translational research to identify and understand the causes of very early onset intestinal disease in children. His research has made it possible for many young children from across Canada and internationally to receive appropriate, personalized treatment, including nutritional therapy and stem cell transplant. These discoveries have already had a major impact on the clinical care of many patients and will fundamentally change the way that children are treated with both rare and common forms of intestinal disease.

The Muise Lab routinely performs whole exome sequencing (WES) or whole genome sequencing (WGS) to screen young children with intestinal disease for known and novel genetic variants. Results are then analyzed using a searchable database to enable rapid understanding of causal, risk, modifying, and treatment specific genes associated with these diseases. In addition to identifying genetic causes for novel diseases, state-of-art technology such as human intestinal organoids (“mini guts”), animal models (mouse and zebrafish), and functional assays are used to further define molecular variants. High-throughput screening (HTS) is also used to search for existing and new therapies that may target a specific gene or pathway.

Muise partners with numerous clinicians and researchers worldwide to identify additional rare disease patients, accelerate research and disease modelling, and promote advanced academic training. This has led to large scale funding and industry partnerships that make his lab an international leader in the study of paediatric gastrointestinal diseases.

Education

  • 2005–2008: Postdoctoral Fellowship, Department of Biochemistry, University of Toronto, Toronto, ON
  • 2004–2008: Fellowship in Paediatric Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, University of Toronto, Toronto, ON
  • 2004: Fellow Royal College Physicians Canada (FRCPC) 
  • 2001–2004: Paediatric Residency, The Hospital for Sick Children, University of Toronto, Toronto, ON
  • 1997–2001: Doctor of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON
  • 1993–1997: Doctor of Philosophy, Department of Biochemistry, Dalhousie University, Halifax, NS
  • 1991–1993: Master of Science, Department of Chemistry, Carleton University, Ottawa, ON
  • 1987–1991: Bachelor of Science, Department of Chemistry, St. Francis Xavier University, Antigonish, NS

Employment

  • 2018: Professor of Biochemistry, University of Toronto, Toronto, ON. 
  • 2018: Professor of Institute of Medical Sciences, University of Toronto, Toronto, ON. 
  • 2018: Professor of Pediatrics, University of Toronto, Toronto, ON. 
  • 2015: Senior Scientist, Program in Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, ON. 
  • 2012: Co-Director of the SickKids IBD Centre of Excellence, The Hospital for Sick Children, Toronto, ON. 

Achievements

International

  • 2018: Honorary Professorship from Shenzhen Children’s Hospital, Shenzhen, China. 
  • 2018: Honorary Professorship from Fudan University, National Children’s Medical Center, Children’s Hospital of Fudan University, Shanghai, China. 
  • 2015: AGA/GRG - Young Investigator Award in Basic Science, American Gastroenterology Association (AGA) and Gastroenterology Research Group (GRG).
  • 2010: George Ferry Young Investigator Development Award, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Society (NASPGHAN). Awarded to meritorious research project in the clinical or basic sciences to study the diseases of the gastrointestinal tract, liver or pancreas and nutritional disorders in children. 

National

  • 2019–2026: Canada Research Chair in Pediatric Inflammatory Bowel Disease (Tier 1), Canadian Institute of Health Research (CIHR), Government of Canada. 
  • 2018: Joe Doupe Award, Canadian Society for Clinical Investigation (CSCI). For excellence in research in the first 10 years of investigators career. 
  • 2014: Institute of Nutrition, Metabolism and Diabetes (INMD) New Investigator Partnership Prize, Canadian Institutes of Health Research. The INMD New Investigator Partnership Prize supports New Investigator Prizes awarded by Partner Organizations 
  • 2014: Canadian Association of Gastroenterology Young Investigator Award, Canadian Association of Gastroenterology. The CAG Young Investigator Award recognizes outstanding contributions to gastroenterology through basic and/or clinical research by a young investigator (less than 45 years of age and less than 7 years of career). 
  • 2011: Future Leaders in IBD (FLIBD) Award Research Grant and one Month Professorship in the Hans Clevers Laboratory in Utrecht, Holland. 
  • 2009–2014: Early Researcher Award, Ontario Ministry of Research and Innovation. 
  • 2008–2012: New Investigator Award, Canadian Institutes of Health Research (CIHR)/Crohn’s and Colitis Foundation of Canada (CCFC)/Canadian Association of Gastroenterology (CAG). 
  • 2008–2012: Career Enhancement Award, Canadian Child Health Clinician Scientist Program (CCHCSP)/CIHR. 
  • 2008: Canadian Research Award for Specialty Residents, Royal College of Physicians and Surgeons of Canada. 
  • 2007: Award for Excellence in Resident Research, Canadian Society for Clinical Investigators (CSCI) and Canadian Institutes for Health Research (CIHR). 

Local (University of Toronto)

  • 2019: Physician Researcher Award for Scientific Accomplishment, Department of Paediatrics, University of Toronto. Recognizes the accomplishments of a physician who has generated a body of research that is exerting a major impact in a field of study.  
  • 2018: Janet Rossant Research Innovation Prize, SickKids Research Institute. In recognition of a significant research achievement from a cross-cutting innovative research endeavor involving two or more SickKids researchers from different disciplines. 
  • 2012: Early Career Physician Researcher Award. Department of Paediatrics, University of Toronto.

Publications

TTC7A: Our group identified the genetic and functional cause of a new disease in infants with very early onset (VEO) IBD: 

  1. Avitzur Y, Guo C, Mastropaolo LA, Bahrami E, Chen H, Zhao Z, Elkadri A, Dhillon S, Murchie R, Fattouh R, Huynh H, Walker JL, Wales PW, Cutz E, Kakuta Y, Dudley J, Kammermeier J, Powrie F, Shah N, Walz C, Nathrath M, Kotlarz D, Puchaka J, Krieger J, Racek T, Kirchner T, Walters TD, Brumell JH, Griffiths AM, Rezaei N, Rashtian P, Najafi M, Monajemzadeh M, Pelsue S, McGovern DP, Uhlig HH, Schadt E, Klein C, Snapper SB, Muise AM. Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease. Gastroenterology. 2014 146(4):1028-1039  
  2. Jardine S, Anderson S, Babcock S, Leung G, Pan J, Dhingani N, Warner N, Guo C, Siddiqui I, Kotlarz D, Dowling JJ, Melnyk R, Snapper SB, Klein C, Thiagarajah JR, Muise AM. Drug screen identifies leflunomide for the treatment of inflammatory bowel disease caused by TTC7A deficiency. Gastroenterology. 2020 158(4):1000-1015

WES in 1000 Pediatric IBD Patients: A proportion of infants and young children with inflammatory bowel diseases (IBD) have subtypes associated with a single gene variant driving disease (monogenic IBD). Knowledge of genetic factors can be used in prognosis and selection of therapy for precision medicine: 

  1. Crowley E, Warner N, Pan J, Khalouei S, Elkadri A, Fiedler K, Foong J, Turinsky AL, Bronte-Tinkew D, Zhang S, Hu J, Tian D, Li D, Regeneron Genetics Center, Horowitz J, Siddiqui I, Upton J, Roifman CM, Church PC, Wall DA, Ramani AK, Kotlarz D, Klein C, Uhlig H, Snapper SB, Gonzaga-Jauregui C, Paterson A, McGovern DP, Brudno M, Walters TD, Griffiths AM, Muise AM. Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated with Monogenic Variants, Identified by Whole-exome Sequencing in 1000 Children at a Single Center, Gastroenterology. 2020 Jun;158(8):2208-2220

ARPC1B: Our lab used WES to identify a cause of severe multisystem disease that includes VEOIBD, platelet abnormalities, eosinophilia, eczema and other indicators of immune disease.  

  1. Kahr WHA, Pluthero FG, Elkadri AR, Warner N, Drobac M, Chen CH, Lo RW, Li Q, Thoeni C, Pan J, Leung G, Lara-Corrales I, Murchie R, Cutz E, Laxer, RM, Upton J, CM Roifman, Young RSM, Brumell JH, Muise AM. Loss of the Arp2/3 complex component ARPC1B causes platelet abnormalities and predisposes to inflammatory disease. Nature Communications. 2017 8:14816

PLVAP: Our group identified the genetic cause of a new human disease that is characterized by severe protein losing enteropathy.  

  1. Elkadri A, Thoeni C, Deharvengt SJ, Murchie R, Guo CH, Stavropoulos JD, Marshall CR, Wales P, Cutz E, Roifman CM, Chitayat D, Avitzur Y, Stan RS, Muise AM. Mutations in Plasmalemma Vesicle Associated Protein (PLVAP) Result in Sieving Protein Losing Enteropathy Characterized by Hypoproteinemia, Hypoalbuminemia, and Hypertriglyceridemia. Cellular and Molecular Gastroenterology and Hepatology. 2015 1(4):381-393 

Canadian Institutes of Health Research (CIHR)

  • Defining the immune dysregulation underlying Pediatric IBD to better diagnose and treat patients 
  • Developing Targeted Therapies for Rare and Common Forms of Inflammatory Bowel Disease 
  • Human Immunology Initiative: Research Teams: Immune Dysregulation in Pediatric Inflammatory Bowel Disease. 

Crohn’s and Colitis Canada

  • Human Immunology Initiative: Research Teams: Immune Dysregulation in Pediatric Inflammatory Bowel Disease. 

Helmsley Charitable Trust

  • Defining and Developing the Therapeutic Pipeline for VEOIBD: Toronto Studies 
  • Defining and Developing the Therapeutic Pipeline for Very Early Onset Inflammatory Bowel Disease: International Academic Centres. 

National Institutes of Health (NIH)

  • Congenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepository. 

Relevant pages

IBD Centre

We lead cutting-edge research and provide leading clinical care and education for paediatric IBD patients.

Cell Biology

We aim to understand how cells function at the molecular level, and how these functions go awry in disease states.

Division of Gastroenterology, Hepatology and Nutrition New Block

Our objective is to brighten the future for children with GHN disorders.

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