Localized real-time sensors for metabolic signaling
The Cambronne lab studies how metabolites are regulated in different parts of the cell to control signaling pathways and gene expression. We develop genetically-encoded fluorescent biosensors for localized and real-time measurements of these metabolites. Our initial work has focused on oxidized nicotinamide adenine dinucleotide (NAD+) for its dual roles in oxidoreductive reactions and as the substrate for NAD+ consuming signaling enzymes. A mitochondrial NAD+ sensor contributed to de-orphaning mitochondrial carrier SLC25A51 as the major transporter of free NAD+ in humans. We found that the selectivity of SLC25A51 for oxidized NAD + can be attributed to charged interactions between the nicotinamide ring and an acidic patch in the central pore of SLC25A51. With its selectivity for oxidized NAD + , SLC25A51 serves as a decoupler for NAD + /NADH ratios in mitochondria, and as such, a promising vulnerability in oxidative cancers such as drug-refractory acute myeloid leukemias. Ongoing studies include understanding how electrogenic properties of SLC25A51 influence its directionality of transport.
Peptide Discovery in Physiology and Metabolism
Dr. Svensson is an Associate Professor of Pathology at Stanford University and the Affinity Group Leader of the Stanford Diabetes Research Center. She received her Ph.D. from Lund University, Sweden and completed her postdoctoral studies at Harvard Medical School and the Dana-Farber Cancer Institute, Boston. Her laboratory studies the physiology and biochemistry of circulating factors and peptide hormones by using a combination of computational, proteomics, cellular, and physiological approaches. Dr. Svensson is a standing member of the NIDDK POMD study section, serves as an Associate Editor for Endocrine Reviews and is on the Editorial Board at Diabetes. She is also a co-founder of Merrifield Therapeutics. Her laboratory is supported by grants from the NIH, American Heart Association, Innovative Medicines Accelerator, SPARK, SDRC, MCHRI, Merck, Eli Lilly, and Pfizer.