Simon Fraser University
Amandio Vieira is interested in the structure and function of biological systems at different levels. In terms of basic research, he and other members of his group study molecular and cellular mechanism of physiological regulation, e.g., biological transport and signaling, genetic and epigenetic control. In much of his work, they develop these interests in the context of nutrition and metabolism: endocytic transport of nutrients, nutritional epigenetics, transport-function relations of hormones and other regulatory/metabolic factors. Basic work on biological transport and transport proteins is also considered in a pathological or therapeutic perspective: basic studies on the endocytic transport of vitamins A, D, and other nutrients, for example, can contribute to a better understanding of the modulation of such transport in cancer cells, or more generally to the identification of pharmaco-modulators of the transport process. One of the nutrient/hormone transport proteins that they study, transthyretin, is also a factor in some amyloidogenic neurodegenerative diseases; its related cellular toxicity mechanisms are being investigated by his group. Another area of interest is that of dietary phytochemicals and human health, e.g., how they contribute to health and longevity, antioxidant activities, and how they may impact pathological processes involved in cancer, cardiovascular, neurodegenerative and other chronic diseases.
The protein transthyretin (formerly, prealbumin) has multiple physiological roles, e.g., in the extracellular transport of thyroid hormones and other compounds, and through its association with other proteins including retinol-binding protein. Misfolded and aggregated transthyretins can have pathological properties and contribute to amyloidogenic diseases including neurodegeneration in hereditary disorders such as amyloidic polyneuropathy. A comparative analysis will be presented based on the results of our studies in terms of (i) the basic biology of transthyretin, e.g., receptor-mediated endocytic transport, (ii) the toxicity of misfolded/ aggregated transthyretins, e.g., disruption of cell membranes and redox balance, and (iii) the moderation of such toxicity by pharmacological compounds including phytochemicals. The presentation will also include biophysical and bioinformatics analyses of transthyretins and other amyloidogenic proteins in an attempt to relate protein structural changes to misfolding/ aggregation and, ultimately, to toxicity and disease.