Broken metabolism

Breaking through the current bottlenecks in fundamental mitochondrial biochemistry, drug design and therapeutic compounds

The health of every living organism is dependent on metabolism, a basic process of life that captures and releases the energy contained in foods we eat to help fuel the body. Within nearly every cell type in the body are tiny, pill-shaped structures called mitochondria. These are the powerhouses for the cells, allowing proper growth, enabling the organs and muscles of the body to function effectively, and providing us with the energy needed for good health. Defects in mitochondrial function can result in serious, often fatal, diseases.

When the varieties of mitochondrial conditions are pooled together, dysfunctional mitochondria become a major source of disease, affecting primarily the very young, but also increasingly older adults as part of the aging process. The defects are centered within the energy transduction pathways of mitochondria, which ultimately produce energy in the form of ATP.

Although the macro elements of the different enzymes are well known, a detailed map and systems biology understanding of the chemical events and their regulation is currently ill-defined. Drug discovery efforts have been hampered due to mitochondria carrying out a distinct type of oxidation-reduction, or redox chemistry.

Traditional medicinal chemistry libraries are devoid of redox compounds and standard systems biology assays omit oxidative elements from their analysis. Our efforts hope to combine both research and translational aspects of discovery in order to break through the current bottlenecks in fundamental mitochondrial biochemistry, drug design and therapeutic compounds.

Our research can be broadly divided into three primary areas:
Understanding nature’s biochemical energy lexicon—the energy code
Identification of chemical scaffolds to enable therapeutic design
Design of systems biology models predictive of human function

Translation aspects of our research program include:
Development of biomarkers to enable optimization and therapeutic evaluation
Chemical optimization using systems biology screens
Advance small molecules into therapeutic evaluation