Research Overview

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What do we study?

Our lab seeks to understand how metabolism superimposes its regulation on cellular processes.

We’re currently focused on the regulation of a key intermediary metabolite, nicotinamide adenine dinucleotide or NAD+.

Why do we care about NAD+?

This dinucleotide is synonymous with life, as there is no sustainable production of ATP without NAD+. Further, it has roles in post-translational modifications as the substrate and adduct used by Parp and Sirtuin enzymes, as well as in 2nd messenger signaling as the precursor for ADP-Ribose and cyclic-ADP-Ribose.

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What is the problem?

Metabolic pathways are highly compartmentalized within tissue and even within a single cell. The challenge is matching the in situ method of study with the biological compartmentalization.

Our approach?

Our group develops and employs genetically encoded fluorescent sensors to measure free NAD+ in different parts of cells. These sensors have high spatial and temporal resolution and are used to take measurements in physiological contexts, both in real-time and non-invasively.

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Most recently, our work with the mitochondrial sensor led to insight into how human mitochondria replenish their NAD+ levels and harness cellular energy (read about it here). This critical pool of NAD+ is typically the last to be depleted at the expense of cytoplasmic or nuclear pools when a cell is faced with stress.

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What is the benefit?

Because maintenance of mitochondrial NAD+ is important for cell heath, how NAD+ gets into mitochondria is likely important in pathogenesis. We’re excited because this new regulatory point we’ve identified could represent a new disease etiology and also holds potential as a target for intervention.