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James  W.  Mandell
Degree(s): M.D., Ph.D.
Graduate School: Cornell University Medical College
Primary Appointment: Associate Professor of Pathology
Research Interests:
Mechanisms of Brain Astroglial Activation in Neural Injury

Email Address: jwm2m@virginia.edu
Biomedical Sciences Graduate Program(s)
  • Neuroscience
  • Molecular Medicine
    • Research Description

    Astrocytes are the most numerous cell type in the brain and perform multiple functions in development and maturity. These cells, also known as astroglia, respond to diverse forms of neural injury with a complex but poorly understood phenotypic change, termed reactive astrogliosis. Like the immune response, astrogliosis has both beneficial and detrimental consequences. The response is classically defined by cell hypertrophy and process extension, glial filament upregulation, and in some cases, proliferation and migration. MAP kinase (MAPK) signaling pathways were classically characterized as effectors of mitogenic and stress stimuli, but are recently implicated in the regulation of cell motility. Our preliminary in vitro data indicate that astroglial process extension and migration are differentially modulated by the ERKMAPK and the p38MAPK pathways. The broad objective of the proposed research program is to define specific roles for and mechanisms by which these two MAPK modules modulate the morphology and motility of reactive astroglia. Experiments employ established in vitro and in vivo techniques as well as Cre/lox conditional gene inactivation approaches. It is anticipated that knowledge gained from these studies will lead to a greater understanding of astroglial involvement in neurological diseases, and lead to development of targeted therapies to therapeutically modulate astrogliosis.

    Selected Publications
  • Carbonell WS, Murase S, Horwitz AF, Mandell JW. Migration of perilesional microglia after focal brain injury and modulation by CC chemokine receptor 5: an in situ time-lapse confocal imaging study. J Neurosci. 2005 Jul 27;25(30):7040-7.
  • Heffron D, Mandell JW. Differential localization of MAPK activated protein kinases RSK1 and MSK1 in mouse brain. Brain Res Mol Brain Res. 2005 May 20;136(1-2):134-41. Epub 2005 Feb 25.
  • Heffron DS, Mandell JW. Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension. Mol Cell Neurosci. 2005 Apr;28(4):779-90.
  • Carbonell WS, Murase SI, Horwitz AF, Mandell JW. Infiltrative microgliosis: activation and long-distance migration of subependymal microglia following periventricular insults. J Neuroinflammation. 2005 Jan 28;2(1):5.
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    Contact Information
      Office Address: PO Box 800904, MR-5, 3220, 
      Office Phone: +1 434-924-2316, +1 434-924-9175
      Fax Phone: +1 434-924-2151

    Other Websites for this mentor:
    http://www.med.virginia.edu/ed-programs/neuroscience/Faculty/mandell-james.html

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