ABSTRACT
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.