Craig Blackstone, M.D., Ph.D.
Cell Biology Section
Building 35, Room 2A-201
35 Convent Drive
Bethesda, MD 20892-3704
Our research group investigates cellular mechanisms underlying inherited neurological disorders, with an emphasis on neuromuscular and movement disorders. In particular, the pathogenesis of hereditary spastic paraplegias, which affect corticospinal motor axons in a length-dependent manner, is an area of very active interest. These disorders comprise well over 50 distinct genetic loci, with over 30 genes identified whose proteins segregate into a few common cellular themes. In addition to an active clinical program assessing new patients with these disorders, we investigate the functions of the disease gene products at the cellular level and in animal models. We have identified that the most common forms of inherited spastic paraplegia are due to mutations in genes encoding proteins with hydrophobic hairpin domains that help shape the distinct morphology of the tubular endoplasmic reticulum network. A number of these proteins as well as other spastic paraplegia proteins implicated in endocytic processes also act as inhibitors of bone morphogenetic protein signaling, providing an exciting translational line of investigation. Our current studies investigate both the disease pathogenic mechanisms as well as the more fundamental aspects of how organelles are shaped in cells, and why this is particularly important for neurons. The common pathogenic themes that are emerging will likely represent novel targets for therapeutic intervention.
Chang CL, Weigel AV, Ioannou MS, Pasolli HA, Xu CS, Peale DR, Shtengel G, Freeman M, Hess HF, Blackstone C, Lippincott-Schwartz J. Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III. J Cell Biol. 2019;218(8):2583-2599.
Nixon-Abell J, Obara CJ, Weigel AV, Li D, Legant WR, Xu CS, Pasolli HA, Harvey K, Hess HF, Betzig E, Blackstone C, Lippincott-Schwartz J. Increased spatiotemporal resolution reveals highly dynamic dense tubular matrices in the peripheral ER. Science. 2016;354(6311).
Lee S, Chang J, Blackstone C. FAM21 directs SNX27-retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus. Nat Commun. 2016;7:10939.
Renvoisé B, Malone B, Falgairolle M, Munasinghe J, Stadler J, Sibilla C, Park SH, Blackstone C. Reep1 null mice reveal a converging role for hereditary spastic paraplegia proteins in lipid droplet regulation. Hum Mol Genet. 2016;25(23):5111-5125.
Chang J, Lee S, Blackstone C. Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Invest. 2014;124(12):5249-62.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Genetics and Genomics
This page was last updated on September 9th, 2019