Dr. Barbara Triggs-Raine received her B.Sc. and Ph.D. degrees from the University of Manitoba. Her post-doctoral training in the molecular basis of human genetic disease was done in the lab of Dr. Roy Gravel at The Hospital for Sick Children in Toronto and the McGill University-Montreal Children’s Hospital Research Institute. Dr. Triggs-Raine is presently Associate Head and Professor in the Department of Biochemistry and Medical Genetics and cross-appointed in the Department of Pediatrics and Child Health at the University of Manitoba. She serves as the Chair of the Research Advisory Committee for Research Manitoba and is a member of the Board for Research Manitoba, the Board of the Children’s Hospital Research Institute of Manitoba, and as a member of the CancerCare Manitoba Foundation’s Program Grants and Awards Committee.
Molecular Pathogenesis of Genetic Disease
The interests of Dr. Triggs-Raine’s lab focuses on the molecular basis of human disease and in particular on genome alterations that impact the metabolism of hyaluronan. They have studied mouse models with deficiencies in enzymes that break down hyaluronan and humans with disorders of hyaluronan degradation. More recently, they have extended their work to include studies of the impact of hyaluronan levels on cancer resistance.
Hyaluronan is a large sugar that is present in the matrix that surrounds all cells in vertebrates. It has a very high rate of turnover in humans, approximately 5 grams per day! Despite these high levels of turnover, the route of degradation is not fully understood. There are several hyaluronidase genes, three of which are broadly expressed in somatic tissues. The Triggs-Raine laboratory has characterized mice deficient in each of these three enzymes, HYAL1, HYAL2, and HYAL3. They are currently working to understand how these enzymes and the exoglycosidases work together in hyaluronan degradation.
HYAL1 deficiency results in a rare lysosomal storage disorder called mucopolysaccharidosis IX which is primarily characterized by joint abnormalities resembling juvenile arthritis. The mouse model with this deficiency also exhibits abnormalities in the knee joints, consistent with HYAL1 have a role for turnover in cells of the joint.
HYAL2 deficient mice have a more severe phenotype, including developmental abnormalities. The characterization of the abnormalities resulting from HYAL2 deficiency is the current focus of much or the research in their laboratory.
For those of you interested in a specific protein, antibodies-online will work with you to determine if any of the antibodies they supply can be validated; it was a great opportunity for us to test a number of antibodies at once!
Example 1| Example 2
Chowdhury B, Hemming R, Faiyaz S, Triggs-Raine B. Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism. Histochem Cell Biol. 2016 Jan;145(1):53-66. doi: 10.1007/s00418-015-1373-8. Epub 2015 Oct 29.
Armistead J, Patel N, Wu X, Hemming R, Chowdhury B, Basra GS Del Bigio MR, Ding H, Triggs-Raine B. (2015) Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression. BBA Mol Basis Dis 1852:1029-1037.
Walia JS, Altaleb N, Bello A, Kruck C, LaFave MC, Varshney GK, Burgess S, Chowdhury B, Hurlbut D, Hemming R, Kobinger GP, Triggs-Raine B. (2015) Long term correction of Sandhoff disease following intravenous delivery of rAAV9 to mouse neonates. Molecular Therapy 23 (3):414-422.
Chowdhury B, Hemming R, Hombach-Klonisch S, Flamion B, Triggs-Raine B. (2013) Murine hyaluronidase 2-deficiency results in extracellular hyaluronan accumulation and severe cardio-pulmonary dysfunction. J. Biol. Chem 288: 520-528.
Triggs-Raine B, Salo T, Zhang H, Wicklow B, and Natowicz MR. Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. (1999) Proc Natl Acad Sci 96: 6296-6300.
Research Publications: PubMed
Characterization of HYAL2 and non-HYAL2 dependent pathways of HA degradation ($40,000/year)
NSERC with D Merz
Pathways of glycosaminoglycan degradation ($26,000/year)
Canadian Foundations for Innovation with A Halayko
Murine MicroCT/Optical Imaging Laboratory ($1,277,982)
Basic Core Platform Fund with A Halayko and R Madziak
U of M Small Animal and Materials Imaging Core Facility ($60,000/yr)
Pathogenesis of, and therapeutic approaches for, hyaluronidase 2 (HYAL2) deficiency ($75,000/year)
University of Manitoba
Determination of the role of hyaluronidase 2 in development and disease ($60,000)
Canadian Cancer Society Research Institute
Evaluation of Hyaluronidase 2 as a Target for Cancer Prevention ($98,981/yr)
University of Manitoba
335-745 Bannatyne Avenue, BMSB
Winnipeg, MB R3E 0J9
Rick Hemming, Research Associate
Wafa Kammouni, Research Associate
Promita Ghosh, MSc Student