The Sedensky laboratory studies mitochondria, which are the parts of the cell that produce energy. When mitochondria do not function well, it can complicate how patients respond to anesthetics, and produce a bewildering array of diseases. The Sedensky laboratory currently uses two models to answer questions about how mitochondria function.
One of these models, C. elegans, is a simple invertebrate that has significant advantages over other models. This animal becomes hypersensitive to volatile anesthetics when a particular step in its mitochondria's ability to make energy is disrupted. When this mitochondrial dysfunction is introduced, the animal has many other hallmarks of mitochondrial disease, including a shortened life span.
There are many mutants in C. elegansthat affect mitochondria, making them an ideal model to begin understanding fundamental processes of mitochondrial function that are shared with the rest of the animal kingdom.
Building on the work in C. elegans, the Sedensky laboratory has found that disrupting the same aspect of mitochondrial function in mice causes them to be hypersensitive to gas anesthetics. The laboratory has characterized a particular mutant and is actively investigating it. This mutant has unusual behaviors when exposed to several anesthetics that are commonly used in patients. The Sedensky laboratory is working closely with Dr. Phil Morgan's laboratory to study this exciting animal model.
Margaret Sedensky, MD, is a principal investigator at Seattle Children's Research Institute and a professor in the Department of Anesthesiology and Pain Medicine at the University of Washington. She came to Seattle Children's in 2008 after working more than 20 years at University Hospitals of Cleveland, Case Western Reserve University School of Medicine. She and Phil Morgan, MD, became recognized as leaders in understanding anesthetic interactions in mitochondrial disease. She received an MD from the University of Colorado School of Medicine. She completed residencies at University Hospitals of Cleveland and completed a research fellowship in anesthesiology at the University of Washington.
Dr. Margaret Sedensky has authored many research papers, including the selected publications listed below. To see more of Sedensky's publications, view a complete list on PubMed.
- Sedensky MM, Meneely PM. Genetic Analysis of Halothane Sensitivity in Caenorhabditis elegans. Science 236:952-954, 1987.
- Kayser EB, Morgan PG, Hoppel CL, Sedensky MM. Mitochondrial Expression and Function of GAS-1 in Caenorhabditis elegans. J. Biol. Chem. 276:20551-20558, 2001.
- Falk, MJ, Kayser, EB, Morgan, PG, Sedensky, MM. Mitochondrial Complex I Function Modulates Volatile Anesthetic Sensitivity in C. elegans. Curr Biol. 16: 1641-45, 2006.
- Falk MJ, Rosenjack JR, Polyak E, Suthammarak W, Chen Z, Morgan PG, Sedensky MM. Subcomplex lambda specifically controls integrated mitochondrial functions in Caenorhabditis elegans. PLoS One 4; e6607, 2009.
- Quintana A, Morgan PG, Kruse SE, Palmiter RD, Sedensky MM. Altered anesthetic sensitivity of mice lacking Ndufs4, a subunit of mitochondrial complex I. PLoS One 7;e42904, 2012
- Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, Uhde L, Hui J, Wall VZ, Gagnidze A, Oh K, Wasko B, Ramos FJ, Palmiter R, Rabinovitch P, Morgan PG, Sedensky MM, Kaeberlein M. mTOR Inhibition by Rapamycin Alleviates Mitochondrial Disease 1 in the Ndufs4 -/- Mouse Model of Leigh Syndrome. Science 2013;342 (6165):1524-8.