CAMBRONNE LAB
Research Overview
Metabolic Control of Cell Signaling and Disease
What do we study?
Our lab seeks to understand how metabolism regulates cellular processes. We elucidate detailed mechanisms for how cells compartmentalize metabolic pathways and metabolic signaling. We specialize in engineering and applying genetically encoded fluorescent biosensors for real-time measurements of metabolites in different parts of cells or tissues.
Why we care?
Cell metabolism concerns almost all aspects of life from survival, regulation of genes, and how cancers develop resistance to current treatments. Alterations in cell metabolism can drive states of health or disease.
What are the challenges we are overcoming?
Biosensors enable types of measurements unattainable with other approaches. We can use biosensors to measure metabolites with subcellular resolution and dynamically in real-time. We can distinguish the free metabolite pool from total metabolite, monitor fluctuations in specific live cells or tissues, and isolate subpopulations with specific metabolic characteristics.
Our Biosensor Approach
The lab has a unique collection of metabolic biosensors. This includes sensors developed by our lab and others to measure nucleotides, central carbon intermediates, amino acids, and signaling metabolites. We currently have an arrayed collection of ~100 unique and barcoded sensors. By identifying critical metabolite fluctuation points, we can uncover both stable and dynamic regulatory mechanisms, and with subcellular resolution within heterogenic samples.
What is the benefit?
The unique data afforded from biosensor measurements has led to foundational discoveries.
Our initial work has focused on nicotinamide adenine dinucleotide (NAD+) for its dual roles in oxidoreductive reactions and as the substrate for NAD+-consuming signaling enzymes.
Our lab developed NAD+ sensors (Cambronne et al 2016 Science), including the first mitochondrial NAD+ biosensor. This new tool led to the first direct intracellular NAD+ measurements, and our co-discovery of a dedicated NAD+ mitochondrial transporter in humans required for harnessing energy from carbon sources and required for mitochondrial ATP production (Luongo et al 2020 Nature).
Since then, we have developed multiple, in-cell assays based on these biosensors. We have elucidated how mitochondrial metabolite concentration gradients are established through voltage (Goyal et al 2025 Sci Advances) and that selective targeting of mitochondrial NAD+ can be a clinically relevant vulnerability in oxidative and resistant cancers. (Lu et al 2024.Cell Metabolism)