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Fletcher A. White, Ph.D.
Assistant Professor
Department of Cell Biology, Neurobiology, and Anatomy
Joint Assistant Professor, Department of Anaesthesiology
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B.A., Baldwin-Wallace
College, Psychology, 1985
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M.Sc., Medical College
of Ohio, Pathology, 1989
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Ph.D., Medical College
of Ohio, Anatomy and Neurobiology, 1995
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Research Fellow,
Neurology, Washington University in St. Louis,1994-1998
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Research Associate,
Anaesthesia & Critical Care, Massachusetts General Hospital
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and Harvard University Medical School,
1998-1999
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Instructor, Neurology
& Anesthesiology, Yale University, 1999-2002
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EMAIL |
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Current Interests |
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Mechanisms of neuropathic
pain, Neuroinflammation, Development of the somatosensory system |
Laboratory Focus |
The focus of my research is on the
peripheral nervous system. Our efforts in peripheral nervous
system research are largely divided between 1) neuropathic pain
mechanisms and 2) the effects of ethanol administration on
trauma-induced neurogenic inflammation of the small intestine.
Damage to peripheral nerves following
trauma or disease has a number of consequences including the
emergence of neuropathic pain. Commonly, neuropathic pain sufferers
experience spontaneous burning pain in and radiating from the area
innervated by the damaged nerves, and an exquisite sensitivity to
light touch stimuli, which are now perceived as painful. These
neuropathic pains are often refractory to conventional analgesic
therapy, with most patients obtaining at best only partial relief.
Unfortunately, neuropathic pains are frequently also very persistent
and do not resolve with time. Thus, neuropathic pain is often an
extremely debilitating condition with a bleak outlook. Our research
focus is on the pathophysiological and neural-immune mechanisms
linking injury to the peripheral nervous system with structural and
chemical alterations in the central nervous system causing
neuropathic pain.
Acute ethanol ingestion commonly contributes to the
etiology of burn injuries as nearly 50% of severe burns occurs in
association with ethanol consumption. Excessive ethanol consumption
is closely linked with trauma-related hospital admissions,
especially in young adults and working-age individuals and
contributes to increased length of hospital stays and mortality
after burn trauma. This increased mortality is largely due to severe
sepsis. Previous studies have shown that disruption of the
intestinal endothelium is a primary mechanism that results in lethal
sepsis and multiple organ failure. Increased postburn endothelial
permeability associated with deranged neutrophil activity are likely
mechanisms that together modulate the postburn intestinal
inflammatory response. As such, we will investigate the degree to
which burn injury alone and burn injury combined with acute ethanol
exposure affects postburn plasma extravasation, myeloperoxidase
levels, and the production of pro-inflammatory cytokines and
chemokines in the ileum. In addition, the protein levels and
cellular localization of the tachykinin, Substance P, a known
neutrophil chemoattractant, will be assayed in the ileum. Substance
P is known to modulate the function of immunocompotent and
inflammatory cells and enhances production of pro-inflammatory
mediators such as cytokines and cell surface receptors.
Importantly, acute ethanol exposure produces a dose-dependent nerve
fiber release of Substance P in intestinal tissue. Based on the
cellular changes present within the small intestines, we propose a
neuropeptide-related mechanism for augmentation of neutrophil
infiltration observed in murine burn injury combined with acute
ethanol exposure when compared with murine burn injury alone.
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Publications |
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White FA, Bhangoo SK, Miller RJ. Chemokines: Integrators of Pain
and Inflammation. Nat Rev Drug Discov 4 (10): 834-44, 2005 |
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White FA,
Waters SM, Sun J, Ma C, Ren D, Ripsch M, Steflik, J, Cortright DN,
LaMotte RH, Miller RJ. Excitatory MCP-1/CCR2 chemokine signaling is
up-regulated by sensory neurons subjected to chronic injury. PNAS, accepted, 2005
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Jellish WS,
Murdoch J, Kindel G, Zhang X, White FA. The effect of clonidine oc
ell survival, glutamate and aspartate release in normo and hyperglycemic
rats after near complete forebrain ischemia. Experimental Brain Research,
accepted 2005
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Chen L,
Grabowski KA, Xin JP, Coleman J, Huang Z, Espiritu B, Alkan S, Xie HB, Zhu
Y, White FA, Clancy J Jr, Huang H. IL-4 induces differentiation and
expansion of Th2 cytokine-producing eosinophils. Journal of Immunology,
172(4): 2059-66, Feb 2004
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White FA.
Peripheral injury-induced central sprouting of myelinated afferents and
CFA-induced neuron phenotype changes are absent in a line of Thy1-YFP
mice. Journal of Pain. 4(2 Suppl): 53, March 2003
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Ma C, Shu Y,
Zheng Z, Chen Y, Yao H, Greenquist KW, White FA, LaMotte RH.
Similar electrophysiological changes in axotomized and neighboring
intact dorsal root ganglion neurons. Journal of Neurophysiology. 89(3):
1588-602, Mar 2003
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Recent Abstracts |
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Combined
alcohol and burn injury differentially regulates bacterial translocation
and inflammatory responses in the mouse
small intestines. Murdoch EL, Fazal N, Ripsch M, Cutro BT, Ramirez L,
Faunce, DE, Kovacs EJ, White FA.
28th
Meeting of the Research Society on Alcohol, June, 2005.
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MCP-1/CCR2 signaling is up-regulated in a
subset of sensory neurons subjected to chronic compression injury of the
DRG.
White FA,
Ren, D, Ma C, Ripsch M, Steflik J, Cortright DN, Waters SM, LaMotte RH,
Miller RJ. Society for Neuroscience,
2004
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Identification of neuropathic pain-associated genes after peripheral
nerve injury in the adult rat: Gene expression analysis using
custom
cDNA microarrays. Waters SM, Steflik J, Cortright DN, Ma C, LaMotte RH,
White FA. Society for Neuroscience,
2004
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Monocyte
chemoattractant protein-1 enhances excitability of nociceptive and non-
ociceptive
neuron in chronically compressed dorsal root ganglia. Sun J, Ma C, Tan
Z,
White FA,
Miller RJ, LaMotte, RH. Society for Neuroscience, 2004
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The effect of
magnesium treatment on spinal cord recovery from traumatic neurological
injury. Zhang X, Jellish WS, White FA. Society for Neuroscience,
2004 |
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