Associate Investigator
Gladstone Institute of Neurological Disease
University of California, San Francisco
Ph.D., University of Athens, Athens, Greece
Phone: 415-734-2512
Fax: 415-355-0824
E-mail:kakassoglou@gladstone.ucsf.edu
Lab Website
Key Words:
Extracellular Proteolysis, Fibrin, Regeneration, Multiple Sclerosis, Neurotrophins
Our laboratory is interested in molecular and cellular mechanisms that regulate nervous tissue regeneration. Regeneration failure in the adult mammalian CNS is not due to an inability of central neurons to elongate and remyelinate, but rather to the non-permissive nature of the CNS environment. Our studies identified fibrin as a novel inhibitory protein that delays nerve regeneration after sciatic nerve injury and showed that fibrin degradation correlates with nerve regeneration, while decreased proteolytic activity in the nervous tissue exacerbates damage. Fibrin, derived from the blood protein fibrinogen, is deposited in the nervous tissue after injury or disease associated with blood-brain barrier leakage. For example, in Multiple Sclerosis fibrin deposition correlates with demyelination and persists in plaques that do not show signs of repair. Our research focuses on the cellular mechanisms and molecular pathways that fibrin uses to affect remyelination and inflammation in the nervous system in an attempt to develop novel therapeutic strategies for neuroinflammatory diseases.
Schachtrup C, Lu P, Lee JK, Jones L, Sachs BD, Ju J, Zheng B,
Akassoglou K. 2007. Fibrinogen inhibits neurite outgrowth via ß3 integrin-mediated transactivation of the EGF receptor.
Proc Natl Acad Scie USA Epub July 2nd.
Sachs B.D., Baillie GS, McCall JR, Passino MA, Schachtrup C, Wallace DA, Dunlop AJ, MacKenzie KF, Klussmann E, Lynch MJ, Sikorski SL, Nuriel T, Tsigelny I, Zhang J, Houslay MD, Chao MV,
Akassoglou K. 2007. p75 Neurotrophin Receptor Regulates Tissue Fibrosis through Inhibition of Plasminogen Activation via a PDE4/cAMP/PKA Pathway. J Cell Biol,
177:1119-1132.
Passino MA, Adams, RA, Sikorski SL,
Akassoglou K. 2007. Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR.
Science,
315:1853-56
Adams RA, Bauer J, Flick MJ, Sikorski SL, Nuriel T, Lassmann H, Degen JL,
Akassoglou K. 2007. The fibrin-derived ?377-395 peptide inhibits microglia activation and reverses relapsing paralysis in central nervous system autoimmune disease.
J Exp Med,
204, 571-582
Akassoglou K, Yu W-M, Akpinar P, Strickland S. 2002. Fibrin inhibits peripheral nerve regeneration by arresting Schwann cell differentiation.
Neuron
33: 861-875.
Akassoglou K, Kombrink KW, Degen JL, Strickland S. 2000. Tissue plasminogen activator-mediated fibrinolysis protects from axonal demyelination after sciatic nerve injury,
J Cell Biol,
149:1157-1166.
Akassoglou K, Bauer J, Kassiotis G, Pasparakis M, Lassmann H, Kollias G and Probert L. 1998. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the CNS of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy.
Am J Pathol
153:801-813.
Akassoglou K, Probert L, Kontogeorgos G and Kollias G. 1997. Astrocyte, but not neuron-specific, transmembrane TNF triggers inflammation and degeneration in the CNS of transgenic mice.
J Immunol
158:438-445.