Support is requested for a Keystone Symposia conference entitled Therapeutic Targeting of Hypoxia-Sensitive Pathways, organized by Drs. Chris W. Pugh, Pablo Wappner, Johanna Myllyharju and Moira K. Whyte to be held April 10-14, 2018 at University of Oxford Mathematical Institute in Oxford, United Kingdom. Tissue oxygen gradients contribute to cellular morphogenesis and, when healthy, cells in different tissues function under differing ambient oxygen conditions. Diseases or environmental challenges can reduce oxygen supply or increase demand, resulting in tissue hypoxia. Adaptive mechanisms have evolved that range from almost instantaneous acute ventilatory changes, through transcriptional events entrained in hours, to epigenetic events with slower effects and genetic adaptations selected across species and over generations. The role of the 2-oxoglutarate dependent dioxygenase enzyme family in influencing many, but not all, of these pleiotropic processes is increasingly recognized, and drugs targeting these enzymes are being evaluated in both experimental and clinical settings. This conference aims to combine the Keystone Symposia brand with the European HypoxiaNET consortium to bring together experts in hypoxia biology from clinical, academic and industrial backgrounds, including trainees, to: 1) address gaps in our knowledge of responses to hypoxia across different timeframes and in different tissues; 2) benefit the field by sharing techniques and reagents to enhance therapeutic targeting of the hypoxic response in general, including via inhibition of oxygen-sensitive enzymes; 3) consider the utility of harnessing these pathways in organ dysfunction, regenerative medicine and to influence immune and inflammatory responses; and 4) disseminate outcomes of ongoing clinical trials and enhance plans for future trials. One of the most significant anticipated outcomes from this conference is that through collaboration, knowledge sharing, and training young investigators/students from diverse backgrounds, the likelihood of successful manipulation of hypoxia pathways to produce clinical benefits in a variety of fields, such as renal anemia, will be considerably enhanced.
The maintenance of oxygen homeostasis is a fundamental physiological challenge and failure of this process is a central component of most human diseases. Recent work has even revealed a different oxygen sensing pathway in plants and a novel class of oxygen-sensitive enzyme in neuroendocrine tissues suggesting that there may be important targets outside the HIF pathway. By holding this Keystone Symposia conference on the theme of hypoxia research, we will promote the sharing of new knowledge, enhance collaborations and training of participants from diverse backgrounds and increase the likelihood, over time, of successful manipulation of hypoxia pathways to produce advances in the treatment of human disease.
