James W. Mandell, M.D., Ph.D.

Associate Professor of Pathology 

 

EDUCATION:

Medical School: Cornell University Medical College, New York, NY.  MD, 1992; Ph.D, 1991 M.D./Ph.D.
 
Graduate School: Postdoctoral Neuroscience, University of Virginia, 1992 - 1994 

Residency: Anatomic Pathology, University of Virginia, 1994 - 1995
1995 - 1996  Chief Resident, Anatomic Pathology, University of Virginia

Fellowship: Fellow, Neuropathology, University of Virginia, 1996 - 1998  

CLINICAL:

Diagnostic neuropathology of neuromuscular disorders, neurodegenerative disease, nervous system neoplasms. See my neuromuscular pathology site.

RESEARCH:

  • Signal transduction mechanisms underlying the astroglial response to neuronal injury and degeneration
  • Roles of astrocytes and other glia in the recognition and phagocytic clearance of degenerating neurons, axons, and synapses during development and degeneration

Astrocytes play an active role in the central nervous system's response to many forms of neural injury and neurodegenerative disease. The underlying mechanisms and functional consequences of this cellular response are poorly understood. My laboratory  investigates transmembrane signaling pathways important for the astroglial response to neuronal injury.   A recent focus is on the recognition and clearance of apoptotic/degenerating neurons during development and degeneration, which is mediated in part by the  BAI1/DOCK/ELMO/Rac1 engulfment pathway.  We utilize techniques of cellular and molecular neuroscience to elucidate the intracellular signal transduction mechanisms and cell biological machinery  involved in these processes. Specific techniques include generation and phenotypic analysis of conditional knockout mice, primary neuronal and glial culture and coculture, DNA transfection, promoter/reporter assays, immunohistochemistry, electron microscopy,  and protein and nucleic acid blotting.

More information on my research laboratory.

  

mandelljuly09
 
Evidence for astroglial engulfment of degenerating axons in the adult mouse olfactory bulb.  Olfactory sensory neuron axons were labeled (red) via anterograde transport of the MiniRuby dye, and astroglia are labeled with anti-GFAP (green).   No uptake is evident in intact glomeruli (A), but astroglial engulfment is observed in glomeruli showing fragmented axonal degeneration (B).
 

REFERENCES:

  • Correa-Cerro LS, Mandell JW. Molecular mechanisms of astrogliosis: new approaches with mouse genetics.  J Neuropathol Exp Neurol. 2007 66(3):169-76. Review.
  • Favero CB and Mandell JW*.  A pharmacological activator of AMP-activated kinase induces astrocyte stellation". Brain Research 2007  1168:1-10
  • Park, D., A.C. Tosello-Trampont, M.R. Elliott, Z. Ma, M. Lu, L. Haney, J.W. Mandell, A. Klibanov, K.S. Ravichandran. 2007. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature. 2007 450:430-4.
  • Mandell JW*. Immunohistochemical assessment of protein phosphorylation state: the dream and the reality. Histochem Cell Biol. 2008 Sep;130(3):465-71.
  • Swerdlow RH, Miller BB, Lopes MB, Mandell JW, Wooten GF, Damgaard P, Manning C, Fowler M, Brashear HR. Autosomal dominant subcortical gliosis presenting as frontotemporal dementia. Neurology. 2009 72:260-7.
  • Mandell JW*, Locke CN; George Glass G,Gianchandani EP, Bourne TD, Schiff D, Amos S, Papin JA Dephosphorylation of beta-arrestin 1 in glioblastomas. J. Neuropath. Exp. Neurol.  2009 68:535-41
  • Glass G, Papin JA, Mandell JW*.  SIMPLE:  A Sequential Immunoperoxidase Labeling and Erasing Method.  J. Histochem. Cytochem. 2009 Apr 13. [Epub ahead of print].
  • Heffron DS, Landreth GE, Samuels IS, Mandell JW*. Brain-Specific Deletion Of ERK2 MAP Kinase Leads to Aberrant Cortical Collagen Deposition.  Am. J. Pathol. 2009, in revision

Neuroscience Graduate Program

A more complete list of Dr. Mandell's publications can be obtained from PubMed