This presentation will cover my journey from discovering an unexplained band on a SDS-PAGE gel analysing chicken serum to elucidation that it was in fact a novel interaction between an important growth factor and a protein that is abundant in the extracellular matrix and in the circulation. We went on to discover that this interaction is conserved in mammals and enables co-activation of two cell surface receptors which stimulate expression of a unique gene signature, which in turns facilitates enhanced cell survival, migration and proliferation, including in skin cells. Given this, we turned our attention to determining whether the technology held potential as a topical therapy for chronic non-healing wounds, such as diabetic foot and venous leg ulcers, a huge and growing healthcare problem. In order to make the therapy cost-effective, we engineered a chimeric protein that retained the key motifs required for these cellular responses within a single protein and formed a start-up, a company that went on to list on the Australian Stock Exchange. The company further developed the technology through scaled-up clinical grade manufacturing to regulatory approval to conduct clinical trials, raising $80M along the way to support technology development. Unfortunately, despite the early promise of the technology in animals studies and early clinical trials in patients with wounds, when the technology was rigorously tested in a large double-blinded randomised Phase 2b clinical trial it failed – so this technology joins the other 70% of therapies that fail to make it through Phase 2 trials. Despite the immense disappointment associated with this failure, I have had an amazing journey. I will share my experiences and learnings, from both a professional and personal perspective.
Zee Upton joined the Institute of Medical Biology in A*STAR, Singapore, as a Research Director in July 2015 to establish, the Tissue Technologies Group. She is a biochemist by training, a tissue engineer, an inventor and entrepreneur who is highly regarded for her research in molecular, biochemical and cellular aspects related to growth factors, extracellular matrix proteins and tissue repair. She is passionate about ensuring research delivers benefits, is taken up and utilised, as well as champions interdisciplinary approaches; she believes that innovation commonly arises in the “white spaces” between disciplines. She also has an interest in “frugal”- or “constraint”-driven innovation, and to this end she is working with collaborators in India and China on projects related to tissue repair, scar remediation and diagnostic technologies. Prof Upton is now the Executive Director of the Institute, and has attracted more than $120M in funding since being in Singapore to establish the “Skin Research Institute of Singapore”, the “Wound Care Innovation for the Tropics” and the “Additive Manufacturing for Biological Materials” Programmes amongst other things.
