Joanna Bakowska, DVM, PhD

  • Associate Professor
  • Molecular Pharmacology and Therapeutics

Genetic, behavioral and cellular approaches to study mechanisms in spastic paraplegias

Hereditary spastic paraplegias are a group of neurological disorders characterized by lower extremity spastic weakness, which is caused by distal axonal degeneration of the upper motor neurons with the longest axons. These disorders afflict tens of thousands of people in the United States. In the past several years, many genes have been shown to be responsible for different types of spastic paraplegias. My research has focused on examining the function of spartin protein, which gene mutation results in Troyer syndrome known also as hereditary spastic paraplegia type 20 (SPG20). Thus far, we discovered that spartin protein is an important component in the intracellular trafficking of receptors. Spartin plays a role in the internalization and sorting of epidermal growth factor receptor (ligand-induced receptor) but not in constitutively recycled receptors. Our studies using fibroblasts derived from patients with Troyer syndrome show that a premature stop codon in the spartin gene results in a complete loss of spartin rather than a truncated form of this protein.

  • Truong,T.; Karlinski,Z. A.; O'Hara,C.; Cabe,M.; Kim,H.; Bakowska,J. C.Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin PLoS ONE 2015 ;10(6):e0130455
  • Karlsson,A. B.; Washington,J.; Dimitrova,V.; Hooper,C.; Shekhtman,A.; Bakowska,J. C.The role of spartin and its novel ubiquitin binding region in DALIS occurrence Molecular biology of the cell 2014 ;25(8):1355-1365
  • Rieger,M. A.; Duellman,T.; Hooper,C.; Ameka,M.; Bakowska,J. C.; Cuevas,B. D.The MEKK1 SWIM domain is a novel substrate receptor for c-Jun ubiquitylation. Biochemical Journal 2012 ;445(3):431-439
  • Rangasamy,V.; Mishra,R.; Sondarva,G.; Das,S.; Lee,T. H.; Bakowska,J. C.; Tzivion,G.; Malter,J. S.; Rana,B.; Lu,K. P.; Kanthasamy,A.; Rana,A.Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function. Proceedings of the National Academy of Sciences of the United States of America 2012 ;109(21):8149-8154
  • Joshi,D. C.; Bakowska,J. C.Determination of mitochondrial membrane potential and reactive oxygen species in live rat cortical neurons Journal of visualized experiments : JoVE 2011 ;(51). pii: 2704. doi(51):10.3791/2704
  • Joshi,D. C.; Bakowska,J. C.SPG20 protein spartin associates with cardiolipin via its plant-related senescence domain and regulates mitochondrial Ca2+ homeostasis. PLoS ONE [Electronic Resource] 2011 ;6(4):e19290
  • Hooper,C.; Puttamadappa,S. S.; Loring,Z.; Shekhtman,A.; Bakowska,J. C.Spartin activates atrophin-1-interacting protein 4 (AIP4) E3 ubiquitin ligase and promotes ubiquitination of adipophilin on lipid droplets. Bmc Biology 2010 ;8:72
  • O'Connor,C.; Pertel,T.; Gray,S.; Robia,S. L.; Bakowska,J. C.; Luban,J.; Campbell,E. M.p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha. Journal of virology 2010 ;84(12):5997-6006
  • Bakowska,J. C.; Wang,H.; Xin,B.; Sumner,C. J.; Blackstone,C.Lack of spartin protein in Troyer syndrome: a loss-of-function disease mechanism?. Archives of Neurology 2008 ;65(4):520-524
  • Bakowska,J. C.; Jupille,H.; Fatheddin,P.; Puertollano,R.; Blackstone,C.Troyer syndrome protein spartin is mono-ubiquitinated and functions in EGF receptor trafficking. Molecular biology of the cell 2007 ;18(5):1683-1692
  • Jeong,K. H.; Bakowska,J. C.; Song,I. O.; Fu,N.; Breakefield,X. O.; Kaiser,U. B.Improvement in reproductive parameters in hypogonadal female mice by regulated gene replacement therapy in the central nervous system. Gene therapy 2007 ;14(14):1092-1101
  • Bakowska,J. C.; Jenkins,R.; Pendleton,J.; Blackstone,C.The Troyer syndrome (SPG20) protein spartin interacts with Eps15. Biochemical & Biophysical Research Communications 2005 ;334(4):1042-1048
  • Bakowska,J. C.; Morrell,J. I.The distribution of mRNA for the short form of the prolactin receptor in the forebrain of the female rat. Brain Research.Molecular Brain Research 2003 ;116(1-2):50-58
  • Bakowska,J. C.; Di Maria,M. V.; Camp,S. M.; Wang,Y.; Allen,P. D.; Breakefield,X. O.Targeted transgene integration into transgenic mouse fibroblasts carrying the full-length human AAVS1 locus mediated by HSV/AAV rep(+) hybrid amplicon vector. Gene therapy 2003 ;10(19):1691-1702