James W. Mandell

Education

  • AB, Cornell University
  • PhD, Cornell University
  • MD, Cornell University
  • Postdoc, University of Virginia

Primary Appointment

  • Associate Professor, Pathology

Contact

Research Interest(s)

Mechanisms of Brain Astroglial Activation in Neural Injury

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

  • Sokolowski J, Chabanon-Hicks C, Han C, Heffron D, Mandell J. Fractalkine is a "find-me" signal released by neurons undergoing ethanol-induced apoptosis. Frontiers in cellular neuroscience. 2014;8 360. PMID: 25426022 | PMCID: PMC4224129
  • Sokolowski J, Gamage K, Heffron D, Leblanc A, Deppmann C, Mandell J. Caspase-mediated cleavage of actin and tubulin is a common feature and sensitive marker of axonal degeneration in neural development and injury. Acta neuropathologica communications. 2014;2 16. PMID: 24507707 | PMCID: PMC3996144
  • Hochreiter-Hufford A, Lee C, Kinchen J, Sokolowski J, Arandjelovic S, Call J, Klibanov A, Yan Z, Mandell J, Ravichandran K. Phosphatidylserine receptor BAI1 and apoptotic cells as new promoters of myoblast fusion. Nature. 2013;497(7448): 263-7. PMID: 23615608 | PMCID: PMC3773542
  • Sokolowski J, Mandell J. Phagocytic clearance in neurodegeneration. The American journal of pathology. 2011;178(4): 1416-28. PMID: 21435432 | PMCID: PMC3078427
  • Daubert E, Heffron D, Mandell J, Condron B. Serotonergic dystrophy induced by excess serotonin. Molecular and cellular neurosciences. 2010;44(3): 297-306. PMID: 20394820 | PMCID: PMC2878889
  • Sokolowski J, Nobles S, Heffron D, Park D, Ravichandran K, Mandell J. Brain-specific angiogenesis inhibitor-1 expression in astrocytes and neurons: implications for its dual function as an apoptotic engulfment receptor. Brain, behavior, and immunity. 2010;25(5): 915-21. PMID: 20888903 | PMCID: PMC3033447
  • Glass G, Papin J, Mandell J. SIMPLE: a sequential immunoperoxidase labeling and erasing method. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2009;57(10): 899-905. PMID: 19365090 | PMCID: PMC2746723
  • Heffron D, Landreth G, Samuels I, Mandell J. Brain-specific deletion of extracellular signal-regulated kinase 2 mitogen-activated protein kinase leads to aberrant cortical collagen deposition. The American journal of pathology. 2009;175(6): 2586-99. PMID: 19893051 | PMCID: PMC2789603
  • Immunohistochemical assessment of protein phosphorylation state: the dream and the reality. Histochemistry and cell biology. 2008;130(3): 465-71. PMID: 18648845 | PMCID: PMC2522329
  • Correa-Cerro L, Mandell J. Molecular mechanisms of astrogliosis: new approaches with mouse genetics. Journal of neuropathology and experimental neurology. 2007;66(3): 169-76. PMID: 17356378
  • Favero C, Mandell J. A pharmacological activator of AMP-activated protein kinase (AMPK) induces astrocyte stellation. Brain research. 2007;1168 1-10. PMID: 17706943 | PMCID: PMC2000700
  • Park D, Tosello-Trampont A, Elliott M, Lu M, Haney L, Ma Z, Klibanov A, Mandell J, Ravichandran K. BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature. 2007;450(7168): 430-4. PMID: 17960134
  • Bourne T, Mandell J, Matsumoto J, Jane J, Lopes M. Primary disseminated leptomeningeal oligodendroglioma with 1p deletion. Case report. Journal of neurosurgery. 2006;105(6): 465-9. PMID: 17184079
  • Hamilton D, Bourne T, Ahmed H, Cousar J, Mandell J, Sheehan J. Follicular lymphoma of the dura: case report. Neurosurgery. 2006;59(3): E703-4; discussion E703-4. PMID: 16955025
  • McFarland K, Wilkes S, Koss S, Ravichandran K, Mandell J. Neural-specific inactivation of ShcA results in increased embryonic neural progenitor apoptosis and microencephaly. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2006;26(30): 7885-97. PMID: 16870734