BBB seminar: Joan Chang
The circadian endosome and collagen-I fibrillogenesis
Wellcome Trust Centre for Cell-Matrix Research, Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, UK
Dysregulation of collagen homeostasis underpins many diseases: excess collagen leads to fibrosis, associated with 45% of all deaths including cancer; conversely, insufficient collagen causes conditions such as poor wound-healing. Despite collagen’s fundamental importance, therapeutics for collagen pathologies have been lacking, due to conceptual hurdles in understanding how collagen is assembled and removed.
Our previous work has identified that the circadian clock controls fibroblast collagen production and assembly through the secretory pathway. Here I will show additional evidence that the endosome of a fibroblast determines the fate of collagen molecules, and that extracellular collagen is recycled to form new matrix. This endocytic recycling route of fibrillogenesis is also enhanced in collagen pathologies, indicating the importance of endosomes in collagen regulation. We are currently carrying out mass spectrometry-based analyses to identify the network of protein machineries involved in collagen trafficking, and investigate how this is involved in fibrosis.
Chairperson: Donald Gullberg, Department of Biomedicine