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Interview with Dr. Aleixo Muise

Brief Biography

Dr. Aleixo Muise received his BSc from St. Francis Xavier University and then went on to complete a PhD in Biochemistry at Dalhousie University. Dr. Muise completed his MD at the University of Toronto and his Pediatric residency at the Hospital for Sick Children and a Subspecialty Fellowship in the Division of Gastroenterology, Hepatology and Nutrition. He also completed Post-doctoral training in the laboratory of Dr. Daniela Rotin. During his Post-doctoral Fellowship, he received the prestigious University of Toronto, Faculty of Medicine, Starr Medal from 2005-07, the Thrasher Research Fund New Investigators Grant, the 2007 Canadian Society for Clinical Investigators (CSCI)/ Canadian Institutes for Health Research (CIHR) Award for Excellence in Resident Research, and the 2008 – Canadian Research Award for Specialty Residents, Royal College of Physicians and Surgeons of Canada.

Research Interests

Inflammatory Bowel Disease

Research Activities:
Dr. Muise's research has focused on understanding the pathogenesis of the inflammatory bowel disease (IBD), which include Crohn's Disease (CD) and Ulcerative Colitis (UC).  Both CD and UC are chronic diseases that affect the intestinal tract of children, adolescents and adults and are often associated with severe morbidity.  The causes of IBD have not yet been identified; however, we now understand that IBD occurs in genetically susceptible individuals and is due to an inappropriate and exaggerated immune response to intestinal bacteria in the setting of impaired intestinal epithelial barrier function.  Recent genetic studies have shown that alterations in bacterial clearance, generalized immune dysfunction, and barrier defense are important in the pathogenesis of IBD.
Dr. Muise’s collaborative research focuses on identifying and understanding the function of candidate genes involved in the pathogenesis of IBD, including recent work on PTPRS, E-cadherin, RAC1, and NCF2. Most recently, Dr. Muise’s clinical interests and research has focused on identifying and understanding the genetic determinants of infantile and very young onset IBD. These studies have led to the formation of the CIHR funded Canadian National Early Onset IBD Cohort Study (NEOPICS) Consortium in which Dr. Muise is the principal investigator. His laboratory continues to work on the genetic and functional role of proteins in the pathogenesis of IBD especially in very young children.

Principal Investigator: Canadian National Early Onset Pediatric IBD Cohort Study (NEOPICS) http://www.neopics.org/

External Funding

Canadian Institute of Health Research – Operating Grant
Title: Genetic and Functional Studies in Very Early Onset-IBD (NEOPICS)

Future Leaders in IBD (FLIBD) Award
Title: Genetic Studies in early onset-IBD

2010 CDHNF/NASPGHAN George Ferry Young Investigator Development Award
Title: Novel pathway analysis in IBD

Ontario Ministry of Research and Innovation - Early Researcher Award (ER08-05-087)
Title: Understanding the Genes Involved in Inflammatory Bowel Disease

Crohn’s and Colitis Foundation of Canada (CCFC)/ Canadian Association of Gastroenterology (CAG)/ Canadian Institute of Health Research (CIHR) - Transition Award
Title: The role of adherens junction protein in IBD.

Crohn’s and Colitis Foundation of America. The Microbiome in IBD: Transformative, Multidisciplinary Clinical and Translational – Team Grant
Title: Determinants of the Microbiome in IBD by the Harvard/Broad Institute – Toronto IBD Consortium

Achievements

• Canadian Medical Research Award for Specialty Residents, Royal College of Physicians and Surgeons of Canada, 2008.
• Award for Excellence in Resident Research, Canadian Society for Clinical Investigators and Canadian Institutes for Health Research, 2007
• Chisolm Memorial Fellowship, Elizabeth Arbuthnot Dayson Fellowship, Nellie L. Farthing Fellowship, William S. Fenwick Fellowship, Miriam Neveren Memorial Award, Joseph M. West Family Memorial Fund, Faculty of Medicine, University of Toronto, 2005-2008.
• Canadian Child Health Clinician Scientist Program, Post-Doctoral Fellowship, 2006-2008.
• Starr Medal, Faculty of Medicine, University of Toronto, 2005, 2006 and 2007.
• Patrick Prize in Biochemistry, Department of Biochemistry, Faculty of Medicine, Dalhousie University, 1999.

Publications

1. He GP*,Muise AM*, Wi A, Ro HS. A eukaryotic transcriptional repressor with carboxypeptidase activity. Nature. 1995, 378(6552):92-6.

2. Muise AM, Storey KB. Reversible phosphorylation of fructose 1,6-bis-phosphatase mediates enzyme role in glycerol metabolism in the freeze avoiding gall moth Epiblema scudderiana. Insect Biochemistry & Molecular Biology. 1997, 27(7):617-23. (PA)

3.*Park J, *Muise AM, He GP, Kim SW, Ro HS. Transcriptional regulation by the g5 subunit of a heterotrimeric G protein during adipogenesis. EMBO Journal. 1999, 18(14):4004-12.

4. Muise AM, Ro HS. Enzymatic characterization of a novel member of the regulatory B-like carboxypeptidase with transcriptional repression function: Stimulation of the enzymatic activity by its target DNA. Biochemical Journal. 1999, 343(2):341-5.

5. Muise AM, Storey KB. Regulation of glycogen synthetase in a freeze avoiding insect: role in cryoprotectant glycerol synthesis. Cryo-Letters. 1999, 20(4):223-8.

6. Muise AM, Storey KB. Regulation of glycogen synthetase in a freeze avoiding insect: role in winter production on glycerol. Archives of Insect Biochemistry and Physiology. 2001, 47(1):29-34.

7.*Kim SW, *Muise AM, Lyons P, Ro HS. Regulation of adipogenesis by a transcriptional repressor that modulates MAP kinase. Journal of Biological Chemistry. 2001, 276(13):10199-206.

8. Muise AM, Storey KB. Regulation of hexokinase in a freeze avoiding insect: role in the winter production. Archives of Insect Biochemistry and Physiology. 2001, 47:29–34.

9. Lyons PJ, Muise AM, Ro HS. MAPK modulates the DNA binding of Adipocyte Enhancer Binding Protein 1. Biochemistry. 2005, 44:926-931.

10. Muise AM, Walters T, Wine W, Griffiths AM, Turner D, Duerr RH, Regueiro MD, Ngan BY, Xu W, Sherman PM,  Silverberg MS, Rotin D. Protein Tyrosine Phosphatase Sigma Is Associated with Ulcerative Colitis. Current Biology. 2007, 17:1212-1218.

11. Muise AM, Walter TD, Glowacka WK, Griffiths AM, Ngan BY, Lan H, Xu W, Silverberg MS, Rotin D. Polymorphisms in E-cadherin (CDH1) result in a mis-localized cytoplasmic protein that is associated with Crohn’s Disease. Gut. 2009, 58(8):1121-7.

12. Imielinski M, Baldassano R, Griffiths A, Russell R, Annese V, Dubinsky M, Kugathasan S, Bradfield J, Walters T, Sleiman P, Kim C, Glessner J, Saeed S, Muise AM, Grundmeier C, Castro M, Latiano PA,  Dallapiccola  B, Stempak J, Taylor K, Kirschner B,  Stephens M, Levine A, Piccoli D, Denson L, Van Limbergen L, Cucchiara S, Guthery S, Wilson D, Grant  S, Daly M, Silverberg M, Satsangi J, Hakonarson H. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nature Genetics. 2009, 41(12):1335-40.

13. Muise AM*, Walters T, Xu W, Shen-Tu, Guo CH, Lam GY, Wolters V, BennitzJ, Van Limbergen J, Fattouh R, Renbaum P, Kasirer Y, Ngan BY, Turner D, Denson LA, Sherman PM, Duerr RH, Cho J, Lees CW, Satsangi J, Wilson DC, Paterson AD, Griffiths AM, Glogauer M, Silverberg MS*, Brumell JH*. Single Nucleotide Polymorphisms that Increase Expression of the GTPase RAC1 are associated with Ulcerative Colitis. Gastroenterology. 2011, 141:633–641.

14.Wolters VM, Xu W, Walters T, Guo CH, GriffithsAM, Silverberg MS, Muise AM. Replication of genetic variation in MYO9B gene in Crohn´s disease. Human Immunology. 2011, 72:592-597.

15. Muise AM*, Xu W, Guo CH, Walters T, Wolters V, FattouhR, Lam GY, Murchie R, NEOPICS, Duerr RH, Cho J, Lees CW, Satsangi J, Wilson DC, GriffithsAM, Glogauer M, Silverberg MS*, Brumell JH*. NADPH oxidase complex and IBD Candidate Gene studies: Identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut. 2011, Online: doi:10.1136/gutjnl-2011-300078. (

16. Turner D, Mack DR, Hyams J, LeLeiko N, Otley A, Markowitz J, Kasirer Y, MuiseAM, Seow C, Silverberg MS, Crandall W, Griffiths AM. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) or both? A systematic evaluation in pediatric ulcerative colitis. Journal Crohn’s and Colitis. 2011, Online: doi:10.1016/j.crohns.2011.05.003

17. Lam GY, Fattouh R, Muise AM, Grinstein S, Higgins DE, Brumell JH. Listeriolysin O Inhibits NOX2 NADPH Oxidase Function During Listeria monocytogenes Infection of Macrophages. Cell Host Microbes. 2011, 10:627-634.

18. Moran C, Walters T, Guo CH, Kugathasan S, Klein C, Wolters VM, Benseler S, Roifman C, Silverberg MS, Griffiths AM, Snapper S*, MuiseAM*. IL-10R Polymorphisms Associated with Very Early-Onset Ulcerative Colitis. Accepted in IBDJ; IBD-12-0143. 2012