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    Katerina Akassoglou, PhD

    TitleProfessor in Residence
    SchoolUCSF School of Medicine
    DepartmentNeurology
    Address1650 Owens Street
    San Francisco CA 94158
    Phone415-734-2512

       Biography 
       Awards and Honors
      The Vilcek Foundation 2009- Vilcek Prize for Creative Promise Finalist Award
      ASPET & Eli Lilly2007- The John J Abel Award in Pharmacology
      The White House2006- Presidential Early Career Award for Scientists and Engineers

       Overview 
       Overview
      Areas of Investigation: Our lab studies mechanisms of neurovascular regulation of inflammation and tissue repair. Our current research focuses on identifying the molecular and cellular interface that blood proteins utilize to interact with nervous system cells and change their functions. Our ultimate goal is to target these interactions for therapeutic intervention in neurologic diseases.


      Significance: Rupture of the vasculature allows the entry of blood proteins into the brain with subsequent edema formation and neuronal damage in a variety of neurologic diseases, such as stroke, multiple sclerosis (MS), Alzheimer's Disease (AD) and spinal cord injury. Our studies aim to unravel the molecular mechanisms of the CNS response to neurovascular changes with the ultimate goal to develop novel therapeutic strategies for neurologic diseases.

      Approaches: We integrate animal modeling, histopathology, tissue culture and biochemistry techniques, as a multifaceted experimental approach to address the biological complexity of disease and repair mechanisms. We have developed in vivo imaging tools of the mouse brain and spinal cord that enable us to monitor disease processes in real time in the living animal.

      Contributions: Our work showed that blood proteins are not merely markers of blood-brain barrier (BBB) disruption, but play a causative role in CNS disease by exerting both pro-inflammatory and neurodegenerative effects. Our studies identified fibrinogen as a potential novel target for therapeutic intervention in neuroinflammatory diseases and led to the design of inhibitory peptides that specifically inhibit the damaging proinflammatory effects of fibrinogen in the CNS without affecting its effects in blood coagulation. Our work also showed that removal of fibrin from the CNS via proteolytic degradation is regulated by the neurotrophin receptor p75NTR via a novel signaling pathway whereby p75NTR directly binds the phosphodieserase isoform PDE4A to compartmentalize cAMP signaling in cells. We also showed novel biological functions for p75NTR as a regulator of cell differentiation that is critical for the progression of fibrosis and tissue repair. Overall, our studies have suggested that bi-directional molecular mechanisms of communication between the blood and the brain determine the degree of damage and the regenerative potential of tissues within and outside of the nervous system.

      Some questions addressed in ongoing studies

      - What is the functional role of BBB disruption in inflammation and neurodegeneration in neurologic diseases?
      - How does fibrinogen affect neuronal and glial functions?
      - Can the beneficial effect of fibrinogen inhibition be exploited therapeutically?
      - What are the biological functions of p75NTR?


       Bibliographic 
       Publications
      Publications by year:
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      1. Chen W, Guo Y, Walker EJ, Shen F, Jun K, Oh SP, Degos V, Lawton MT, Tihan T, Davalos D, Akassoglou K, Nelson J, Pile-Spellman J, Su H, Young WL. Reduced Mural Cell Coverage and Impaired Vessel Integrity After Angiogenic Stimulation in the Alk1-deficient Brain. Arterioscler Thromb Vasc Biol. 2013 Feb; 33(2):305-10.
        View in: PubMed
      2. Shimazu T, Hirschey MD, Newman J, He W, Shirakawa K, Le Moan N, Grueter CA, Lim H, Saunders LR, Stevens RD, Newgard CB, Farese RV, de Cabo R, Ulrich S, Akassoglou K, Verdin E. Suppression of Oxidative Stress by ß-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor. Science. 2013 Jan 11; 339(6116):211-4.
        View in: PubMed
      3. Gut P, Baeza-Raja B, Andersson O, Hasenkamp L, Hsiao J, Hesselson D, Akassoglou K, Verdin E, Hirschey MD, Stainier DY. Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism. Nat Chem Biol. 2013 Feb; 9(2):97-104.
        View in: PubMed
      4. Kwan W, Träger U, Davalos D, Chou A, Bouchard J, Andre R, Miller A, Weiss A, Giorgini F, Cheah C, Möller T, Stella N, Akassoglou K, Tabrizi SJ, Muchowski PJ. Mutant huntingtin impairs immune cell migration in Huntington disease. J Clin Invest. 2012 Dec 3; 122(12):4737-47.
        View in: PubMed
      5. Baeza-Raja B, Akassoglou K. Glucose homeostasis and p75NTR: the sweet side of neurotrophin receptor signaling. Cell Cycle. 2012 Sep 1; 11(17):3151-2.
        View in: PubMed
      6. Baeza-Raja B, Li P, Le Moan N, Sachs BD, Schachtrup C, Davalos D, Vagena E, Bridges D, Kim C, Saltiel AR, Olefsky JM, Akassoglou K. p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity. Proc Natl Acad Sci U S A. 2012 Apr 10; 109(15):5838-43.
        View in: PubMed
      7. Le Moan N, Baeza-Raja B, Akassoglou K. p75 (NTR) and hypoxia: a breath of fresh air in neurotrophin receptor signaling. Cell Cycle. 2012 Mar 1; 11(5):829-30.
        View in: PubMed
      8. Pearn ML, Hu Y, Niesman IR, Patel HH, Drummond JC, Roth DM, Akassoglou K, Patel PM, Head BP. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology. 2012 Feb; 116(2):352-61.
        View in: PubMed
      9. Davalos D, Akassoglou K. In vivo imaging of the mouse spinal cord using two-photon microscopy. J Vis Exp. 2012; (59):e2760.
        View in: PubMed
      10. Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K. Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun. 2012; 3:1227.
        View in: PubMed
      11. Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, Jonsson Fagerlund M, Charo IF, Akassoglou K, Maze M. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011 Dec; 70(6):986-95.
        View in: PubMed
      12. Le Moan N, Houslay DM, Christian F, Houslay MD, Akassoglou K. Oxygen-dependent cleavage of the p75 neurotrophin receptor triggers stabilization of HIF-1a. Mol Cell. 2011 Nov 4; 44(3):476-90.
        View in: PubMed
      13. Baeten KM, Akassoglou K. Extracellular matrix and matrix receptors in blood-brain barrier formation and stroke. Dev Neurobiol. 2011 Nov; 71(11):1018-39.
        View in: PubMed
      14. Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol. 2012 Jan; 34(1):43-62.
        View in: PubMed
      15. Schachtrup C, Le Moan N, Passino MA, Akassoglou K. Hepatic stellate cells and astrocytes: Stars of scar formation and tissue repair. Cell Cycle. 2011 Jun 1; 10(11):1764-71.
        View in: PubMed
      16. Drew PJ, Shih AY, Driscoll JD, Knutsen PM, Blinder P, Davalos D, Akassoglou K, Tsai PS, Kleinfeld D. Chronic optical access through a polished and reinforced thinned skull. Nat Methods. 2010 Dec; 7(12):981-4.
        View in: PubMed
      17. Schachtrup C, Ryu JK, Helmrick MJ, Vagena E, Galanakis DK, Degen JL, Margolis RU, Akassoglou K. Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage. J Neurosci. 2010 Apr 28; 30(17):5843-54.
        View in: PubMed
      18. Ryu JK, Davalos D, Akassoglou K. Fibrinogen signal transduction in the nervous system. J Thromb Haemost. 2009 Jul; 7 Suppl 1:151-4.
        View in: PubMed
      19. Friedman B, Schachtrup C, Tsai PS, Shih AY, Akassoglou K, Kleinfeld D, Lyden PD. Acute vascular disruption and aquaporin 4 loss after stroke. Stroke. 2009 Jun; 40(6):2182-90.
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      20. Gaultier A, Wu X, Le Moan N, Takimoto S, Mukandala G, Akassoglou K, Campana WM, Gonias SL. Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis. J Cell Sci. 2009 Apr 15; 122(Pt 8):1155-62.
        View in: PubMed
      21. Xu M, Remillard CV, Sachs BD, Makino A, Platoshyn O, Yao W, Dillmann WH, Akassoglou K, Yuan JX. p75 neurotrophin receptor regulates agonist-induced pulmonary vasoconstriction. Am J Physiol Heart Circ Physiol. 2008 Oct; 295(4):H1529-38.
        View in: PubMed
      22. Rius J, Guma M, Schachtrup C, Akassoglou K, Zinkernagel AS, Nizet V, Johnson RS, Haddad GG, Karin M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature. 2008 Jun 5; 453(7196):807-11.
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      23. Davalos D, Lee JK, Smith WB, Brinkman B, Ellisman MH, Zheng B, Akassoglou K. Stable in vivo imaging of densely populated glia, axons and blood vessels in the mouse spinal cord using two-photon microscopy. J Neurosci Methods. 2008 Mar 30; 169(1):1-7.
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      24. Xu M, Platoshyn O, Makino A, Dillmann WH, Akassoglou K, Remillard CV, Yuan JX. Characterization of agonist-induced vasoconstriction in mouse pulmonary artery. Am J Physiol Heart Circ Physiol. 2008 Jan; 294(1):H220-8.
        View in: PubMed
      25. Sachs BD, Akassoglou K. Regulation of cAMP by the p75 neurotrophin receptor: insight into drug design of selective phosphodiesterase inhibitors. Biochem Soc Trans. 2007 Nov; 35(Pt 5):1273-7.
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      26. Schachtrup C, Lu P, Jones LL, Lee JK, Lu J, Sachs BD, Zheng B, Akassoglou K. Fibrinogen inhibits neurite outgrowth via beta 3 integrin-mediated phosphorylation of the EGF receptor. Proc Natl Acad Sci U S A. 2007 Jul 10; 104(28):11814-9.
        View in: PubMed
      27. Sachs BD, 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. p75 neurotrophin receptor regulates tissue fibrosis through inhibition of plasminogen activation via a PDE4/cAMP/PKA pathway. J Cell Biol. 2007 Jun 18; 177(6):1119-32.
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      28. Passino MA, Adams RA, Sikorski SL, Akassoglou K. Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR. Science. 2007 Mar 30; 315(5820):1853-6.
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      29. Adams RA, Bauer J, Flick MJ, Sikorski SL, Nuriel T, Lassmann H, Degen JL, Akassoglou K. The fibrin-derived gamma377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease. J Exp Med. 2007 Mar 19; 204(3):571-82.
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      30. Adams RA, Schachtrup C, Davalos D, Tsigelny I, Akassoglou K. Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis. Curr Med Chem. 2007; 14(27):2925-36.
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      31. Arthur DB, Akassoglou K, Insel PA. P2Y2 and TrkA receptors interact with Src family kinase for neuronal differentiation. Biochem Biophys Res Commun. 2006 Sep 1; 347(3):678-82.
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      32. Arthur DB, Georgi S, Akassoglou K, Insel PA. Inhibition of apoptosis by P2Y2 receptor activation: novel pathways for neuronal survival. J Neurosci. 2006 Apr 5; 26(14):3798-804.
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      33. Arthur DB, Akassoglou K, Insel PA. P2Y2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation. Proc Natl Acad Sci U S A. 2005 Dec 27; 102(52):19138-43.
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      34. Akassoglou K. Nerve growth factor-independent neuronal survival: a role for NO donors. Mol Pharmacol. 2005 Oct; 68(4):952-5.
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      35. Adams RA, Passino M, Sachs BD, Nuriel T, Akassoglou K. Fibrin mechanisms and functions in nervous system pathology. Mol Interv. 2004 Jun; 4(3):163-76.
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      36. Akassoglou K, Adams RA, Bauer J, Mercado P, Tseveleki V, Lassmann H, Probert L, Strickland S. Fibrin depletion decreases inflammation and delays the onset of demyelination in a tumor necrosis factor transgenic mouse model for multiple sclerosis. Proc Natl Acad Sci U S A. 2004 Apr 27; 101(17):6698-703.
        View in: PubMed
      37. Akassoglou K, Malester B, Xu J, Tessarollo L, Rosenbluth J, Chao MV. Brain-specific deletion of neuropathy target esterase/swisscheese results in neurodegeneration. Proc Natl Acad Sci U S A. 2004 Apr 6; 101(14):5075-80.
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      38. Akassoglou K, Akpinar P, Murray S, Strickland S. Fibrin is a regulator of Schwann cell migration after sciatic nerve injury in mice. Neurosci Lett. 2003 Mar 6; 338(3):185-8.
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      39. Akassoglou K, Douni E, Bauer J, Lassmann H, Kollias G, Probert L. Exclusive tumor necrosis factor (TNF) signaling by the p75TNF receptor triggers inflammatory ischemia in the CNS of transgenic mice. Proc Natl Acad Sci U S A. 2003 Jan 21; 100(2):709-14.
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      40. Akassoglou K, Yu WM, Akpinar P, Strickland S. Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation. Neuron. 2002 Mar 14; 33(6):861-75.
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      41. Akassoglou K, Strickland S. Nervous system pathology: the fibrin perspective. Biol Chem. 2002 Jan; 383(1):37-45.
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      42. Probert L, Akassoglou K. Glial expression of tumor necrosis factor in transgenic animals: how do these models reflect the "normal situation"? Glia. 2001 Nov; 36(2):212-9.
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      43. Brodsky S, Chen J, Lee A, Akassoglou K, Norman J, Goligorsky MS. Plasmin-dependent and -independent effects of plasminogen activators and inhibitor-1 on ex vivo angiogenesis. Am J Physiol Heart Circ Physiol. 2001 Oct; 281(4):H1784-92.
        View in: PubMed
      44. Probert L, Eugster HP, Akassoglou K, Bauer J, Frei K, Lassmann H, Fontana A. TNFR1 signalling is critical for the development of demyelination and the limitation of T-cell responses during immune-mediated CNS disease. Brain. 2000 Oct; 123 ( Pt 10):2005-19.
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      45. Akassoglou K, Kombrinck KW, Degen JL, Strickland S. Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury. J Cell Biol. 2000 May 29; 149(5):1157-66.
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      46. Aloe L, Properzi F, Probert L, Akassoglou K, Kassiotis G, Micera A, Fiore M. Learning abilities, NGF and BDNF brain levels in two lines of TNF-alpha transgenic mice, one characterized by neurological disorders, the other phenotypically normal. Brain Res. 1999 Sep 4; 840(1-2):125-37.
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      47. Kassiotis G, Bauer J, Akassoglou K, Lassmann H, Kollias G, Probert L. A tumor necrosis factor-induced model of human primary demyelinating diseases develops in immunodeficient mice. Eur J Immunol. 1999 Mar; 29(3):912-7.
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      48. Akassoglou K, Bauer J, Kassiotis G, Lassmann H, Kollias G, Probert L. Transgenic models of TNF induced demyelination. Adv Exp Med Biol. 1999; 468:245-59.
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      49. Akassoglou K, Bauer J, Kassiotis G, Pasparakis M, Lassmann H, Kollias G, Probert L. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. Am J Pathol. 1998 Sep; 153(3):801-13.
        View in: PubMed
      50. Probert L, Akassoglou K, Kassiotis G, Pasparakis M, Alexopoulou L, Kollias G. TNF-alpha transgenic and knockout models of CNS inflammation and degeneration. J Neuroimmunol. 1997 Feb; 72(2):137-41.
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      51. Akassoglou K, Probert L, Kontogeorgos G, Kollias G. Astrocyte-specific but not neuron-specific transmembrane TNF triggers inflammation and degeneration in the central nervous system of transgenic mice. J Immunol. 1997 Jan 1; 158(1):438-45.
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      52. Fiore M, Probert L, Kollias G, Akassoglou K, Alleva E, Aloe L. Neurobehavioral alterations in developing transgenic mice expressing TNF-alpha in the brain. Brain Behav Immun. 1996 Jun; 10(2):126-38.
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      53. Probert L, Akassoglou K, Alexopoulou L, Douni E, Haralambous S, Hill S, Kassiotis G, Kontoyiannis D, Pasparakis M, Plows D, Kollias G. Dissection of the pathologies induced by transmembrane and wild-type tumor necrosis factor in transgenic mice. J Leukoc Biol. 1996 Apr; 59(4):518-25.
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      54. Probert L, Akassoglou K, Pasparakis M, Kontogeorgos G, Kollias G. Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. Proc Natl Acad Sci U S A. 1995 Nov 21; 92(24):11294-8.
        View in: PubMed
      55. Douni E, Akassoglou K, Alexopoulou L, Georgopoulos S, Haralambous S, Hill S, Kassiotis G, Kontoyiannis D, Pasparakis M, Plows D, Probert L, Kollias G. Transgenic and knockout analyses of the role of TNF in immune regulation and disease pathogenesis. J Inflamm. 1995-1996; 47(1-2):27-38.
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