Brief Biography

Dr. Aleixo Muise completed his BSc at Sr. Francis Xavier University and his PhD in Biochemistry at Dalhousie University.  Dr. Muise obtained his MD at the University of Toronto and then completed is Pediatric Residency and subspecialty training in the Division of Gastroenterology, Hepatology and Nutrition at SickKids.  Dr. Muise was recently appointed as Assistant Professor in the Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, and as a Scientist-Track Investigator in the Program in Cell Biology, Research Institute, Hospital for Sick Children, University of Toronto.

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.

His collaborative work focuses on understanding the role of IBD genes identified in both genome wide association studies (GWAS) and candidate gene approaches.  We have recently identified an association with IBD and single nucleotide polymorphisms (SNPs) in the PTPRS (encoding PTPsigma) and in the CDH1 (encoding E-cadherin) genes.  We have also shown through genetic and functional studies that these SNPs result in altered protein production that, in part, ultimately leads to the development of IBD.  We plan on further studying these proteins (and others) so as to determine their specific role in the development of IBD.

Ongoing Research Projects:

1. IBD Genetic Studies: Collaboration with Drs. Walters, Griffiths, Brumell, and Silverberg.
2. Functional IBD Studies: Collaboration with Drs. Rotin, Brumell, and Sherman.
3. IBD Translational Projects: Collaboration with Drs. Walters, Griffiths, and Benchimol.

External Funding

• Crohn's and Colitis Foundation of Canada (CCFC)/ Canadian Association of Gastroenterology (CAG)/ Canadian Institutes of Health Research (CIHR) - Transition Award, 2008-2012.
• Canadian Child Health Clinician Scientist Program (CCHCSP)/ CIHR - Career Enhancement Operating Grant, 2008-2012. 

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

Selected Publications:

1. Muise A, He GP, Wi A, Ro HS. A eukaryotic transcriptional repressor with carboxypeptidase activity. Nature. 1995, 378(6552):92-6.
2. Muise A, Park J, 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.
3. Muise A, Ro HS. Enzymatic characterization of a novel member of the regulatory B-like carboxypeptidase with transcriptional repression function: Stimuation of the enzymatic activity by its target DNA. Biochemical Journal. 1999, 343(2):341-5.
4. Muise A, Kim SW, Lyons P, Ro HS. Regulation of adipogenesis by a transcriptional repressor that modulates MAP kinase. Journal of Biological Chemistry. 2001, 276(13):10199-206.
5. Lyons PJ, Muise AM, Ro HS. MAPK modulates the DNA binding of Adipocyte Enhancer Binding Protein 1. Biochemistry. 2005, 44:926-931.
6. Muise AM, Turner D, Wine E, Kim P, Marcon M, Ling S. Biliary Atresia and Choledochal Cyst: Implications for Classification. Clinical Gastroenterology and Hepatology. 2006, 4(11):1411-1414.
7. Turner D, Hammerman C, Bernard R, Schlesinge Y, Wine E, Muise A, Schimmel MS. Low levels of procalcitonin during episodes of necrotizing enterocolitis. Digestive Diseases and Sciences. 2007, 52(11):2972-6.
8. 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.
9. Muise AM, Rotin D. Apical Junction Complex Proteins and Ulcerative Colitis: a focus on the PTPRS gene.  Expert Review of Molecular Diagnostics. 2008, 8(4) 465-477.
10. Muise AM, Walter TD, Glowacka WK, 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, Apr 26. [Epub ahead of print]