The PAS Sensor Family and Human Health

PROJECT SUMMARY
This R35 proposal is designed to consolidate two R01 programs, ES005703 and ES020668 into one
program with an emphasis on understanding how environment influences human health through the PAS
sensor family of proteins. Our approach is to use a highly experienced team, a broad spectrum of
biochemical and genetic reagents, a transdisciplinary approach, and the expertise of an array of
collaborators and clinician scientists to define the roles that PAS sensors play in environmentally influenced
disease states such as cancer, infertility, obesity, diabetes and inflammatory bowel disease. Our
overarching idea is that PAS sensors, and their related environmental signals, are impinging on almost
every aspect of human health through their capacity as sensors of circadian time, oxygen status, chemical
exposure and microbiome changes. We propose that by understanding these pathways, we can not only
identify important gene by environment, and environment by environment interactions, but that we can use
this information to develop intervention strategies in numerous environmental scenarios likely to be causing
human morbidity. Our vision is to understand these pathways through the prism of the Ah receptor (AHR)
and through the overarching idea that these pathways are in fact interacting through shared partners,
cofactors or ligands. We propose that the insights gained from the R35 will ultimately be useful in
intervention strategies to manipulate these pathways via therapeutics or to guide/modify human behavior or
the human environment in a manner that is most beneficial to sensitive populations. Over the next eight
years, this consolidated R35 should give us the freedom and power to make considerable advances in our
understanding of PAS sensors and how they influence human health.

Grant Number: 5R35ES028377-08
NIH Institute/Center: NIH
Principal Investigator: CHRISTOPHER BRADFIELD