Christiane Auray-Blais, LL. M., Ph. D.
Biomarker Discovery, Characterisation and Quantification Using Mass Spectrometry Approaches
Lysosomal storage disorders comprise over 50 different hereditary metabolic diseases, such as Fabry disease, an X-linked disorder caused by the enzyme deficiency of alpha-galactosidase A. Until now, more than 660 mutations have been detected. Clinical manifestations of the disease are quite heterogeneous. Patients may present cardiac, kidney, CNS involvement, dermatololgy, GI manifestations, etc. Biomarkers are important indicators for the early detection of affected patients, as well as monitoring the response to treatment and/or progression of disease.
Biochemist and Director of the Mass Urinary Screening Program at CHUS, the investigator Christiane Auray-Blais has developed a simple method, using tandem mass spectrometry, for the analysis of one biomarker, globotriaosylceramide (Gb3), in urine samples collected on filter paper. This method has led to a protocol for high-risk screening of Fabry patients which is used worldwide. Recent studies using time-of-flight mass spectrometry have led to the discovery of novel biomarkers for individuals presenting cardiac variants of Fabry disease. These biomarkers are analogs of globotriaosylsphingosine (Lyso-Gb3). A relative quantification of these biomarkers has demonstrated that they are excreted in urine in greater quantities than lyso-Gb3 itself. In all, 18 isoforms/analogs of Gb3 and 7 novel analogs of lyso-Gb3 have been detected. This biomarker discovery and their quantification will lead to the development of new tests which will be validated and transferred to the clinical field to be offered to the population, and also in a Fabry gene therapy research project started last year. Moreover, a metabolic pathway has been proposed showing a possible link between Gb3 and lyso-Gb3. Novel methodologies have also been developed by tandem mass spectrometry for the quantification of glycosaminoglycans, such as dermatan sulfate and heparan sulfate for mucopolysaccharidoses type I, II and VI patients for high-risk and eventually mass screening. The ultimate goal being preventive genetic medicine in targeted populations.
As Scientific Director of the Waters-CHUS Expertise Centre in Clinical Mass Spectrometry, Doctor Auray-Blais has developed and implemented other projects with her colleagues related to prematurity in newborns, gestational diabetes, asthma, and eventually autism amongst others.
- Excellence Award 2008, ADESAQ, Best Ph.D. thesis in the province of Québec
- Excellence Award 2007, CHUS, Multidisciplinary Council Category
- Example Award 2005, Sherbrooke Rehabilitation Center, Qc
- Research Partnership with CIHR, Genzyme, Shire HGT and Waters Corporation from 2008 to 2013: more than 2 M$
- Over 170 publications and abstracts, some in prestigious journals (Science, Journal of Clinical Investigation, etc.)
Know-How & Opportunities for Collaboration
- Expertise in mass screening for inborn errors of metabolism in Quebec (2 950 000 newborns screened over the years)
- Implementation and development of the Waters-CHUS Expertise Centre in Clinical Mass Spectrometry
- Metabolomics and discovery of biomarkers for lysosomal storage disorders and others
- Quantification and validation of novel methodologies for biomarkers as new tests to be transferred to the clinic
- Development of a new course in mass spectrometry offered to graduate students entitled: "Mass Spectrometry and Applications in Health"
- Expertise in ethics, genetics and biobanking