Grant: Emerging Team Grant: Regenerative Medicine and Nanomedicine - LOI

Fibrosis is the deposition of fibre-like scar tissue in a given organ. It is associated with a large number of diseases, infectious and inflammatory conditions as well as trauma. For example, there are over 140 conditions associated with the development of lung fibrosis. Fibrosis can take place in essentially all organs, with lung, gut liver and hearth the most relevant for the health system. The development of this hard scar tissue strongly impairs organ function and invariably leads to chronic disease requiring life-long and costly therapies. In addition, it alters the tissue environment in a way that strongly inhibits the ability of transplanted stem cells to engraft, and of local stem cells to regenerate damage. In short, the presence of fibrosis is a major obstacle to any regenerative medicine approach, whether based on delivering cells generated from ES cells or on using drugs to stimulate the stem cells already resident in the tissue. Surprisingly, while the associations of fibrosis with several diseases are well known, very little information exists on how exactly these diseases trigger its formation. Here we propose to assemble a multidisciplinary team of scientists to 1) identify the cells responsible for the appearance of fibrosis (fibrogenic stem cells) in animal models of lung, gut and hearth disease, and verify the validity of our conclusions by analyzing human patient samples. 2) Identify the signals acting on these cells and triggering the formation of scar tissue 3) Exploit this information to screen for compounds that may inhibit these cells and reduce fibre deposition in the tissues. To our knowledge, this is the first concerted attempt to investigate the cellular causes of fibrosis. Should this approach be successful, it will enable us to reduce fibrosis development in patients thus greatly increasing the likelihood that regenerative therapies will be successful.