Metabolomics Of The Extracellular Matrix As Diagnostic Markers Of Disease | 807
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The Extracellular Matrix (ECM) is a dynamic and complex mixture of glycoproteins produced by cells in response to the
biological signals present in the surrounding local environment. The end result of this precisely orchestrated process has
been referred to as ECM regeneration and has been shown to be altered in many disease states. Proteoglycans (PGs) are a group
of ECM molecules that are characterized by their carbohydrate modifications known as glycosaminoglycans (GAGs), and which
are linear alternating co-polymers of hexuronic acid and hexoxasamine that are differentially modified with sulfate that provide
both molecular weight dispersity and charge heterogeneity. Our fundamental hypothesis is that the protein and carbohydrate
structures of PGs change in response to disease and that we can use these changes of structure as a diagnostic of disease. We have
shown that a chondroitin sulfate proteoglycan (CSPG), lubricin undergoes alternative splicing and that this might be in response
to arthritis. We have also shown that another PG bikunin, which is important in incorparating hyaluronan into the ECM has
different CS sulfation patterns in arthritis, which affect its biological function. Another example from our laboratory focuses in
the structure of perlecan, a heparan sulfate proteoglycans (HSPG) that can be decorated with HS, CS or keratan sulfate, which
have profound effects on its ability to bind and signal growth factors. We have undertaken a PCR-based, immuno-detection study
and have shown that perlecan undergoes alternative splicing that results in forms with different biological functions and forms
that are assocated with disease.
John M Whitelock graduated with a Ph.D. from the University of Technology, Sydney in 1991, and after completing post-doctoral studies at the
University of Alabama, Birmingham and the Commonwealth Scientific Industrial Research Organization (CSIRO) is now the Head of the Graduate
School of Biomedical Engineering at the University of New South Wales. His research focuses on the roles of the extracellular matrix and the way
tissues and organs are generated during development and how this relates to the regenerative processes seen in disease. He has authored over
200 conference presentations and published over 75 journal articles in international peer-reviewed journals.
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