Chemical Physiology

The Chemical Physiology Department aims to bring together researchers dedicated to developing and utilizing cutting-edge chemical technologies to address biological problems of exceptional complexity and medical relevance. The success of genome sequencing projects has propelled 21st century biologists and chemists into an era where focus has shifted from the discovery of new genes to the functional characterization of gene products. Indeed, of the more than 20,000 genes found in the human genome, at least half are lacking functional annotation. This finding underscores how little we still understand about the molecular basis of life and its disorders, while at the same time highlighting the tremendous opportunity that awaits post-genomic researchers interested in advancing new methods to characterize gene and protein function on a global scale.

The goal of the Chemical Physiology Department is to discover, characterize, and eventually control the biochemical pathways that regulate higher-order physiological and pathological processes. We are committed to creating innovative analytical and pharmacological tools to address biological problems at multiple levels of inquiry, toward the purpose of moving seamlessly from molecules to cellular pathways to living systems. Emergent from these studies will be a detailed understanding of the chemistry of life, along with the requisite tools to probe pathways and restore their dysregulated states in human disease for therapeutic gain.

Specific examples of the research ongoing in the Chemical Physiology Department include:

• Development of mass spectrometry methods for the large-scale analysis of protein expression, modifications, and interactions
• Creation of molecular probes of cell surface receptors to elucidate their physiological ligands and membrane microdomain organization
• Using high-throughput, small-molecule screens together with chemistry to generate potent and selective proof-of-concept chemical probes with cellular or in vivo activities defining potential control points in health and disease
• Development of chemical tools for profiling enzyme and small-molecule function in native biological systems
• Elucidation of the molecular, cellular, and (patho)physiological processes regulated by nuclear receptor signaling pathways
• Determination of the role that nuclear receptors play as integrators of higher-order metabolic states
• Investigation of the function of arginine post-translational modification in autoimmunity and other pathophysiological processes.