Fletcher A. White, Ph.D.

Professor and Vergil K. Stoelting Chair of Anesthesia
Professor of Pharmacology & Toxicology

Education / Training:
M.S.: Medical College of Ohio, Toledo, OH (Pathology, 1990)
Ph.D.: Medical College of Ohio Toledo, OH (Anatomy/Neurobiology, 1994)
Postdoctoral Fellowship: Washington University, St. Louis, MO (Neurology, 1994-1998)
Postdoctoral Fellowship: Massachusetts General Hospital/Harvard Medical School, Boston, MA (Anesthesia,1998-1999)

Cytokine/Chemokine signaling and the sensory neuron.

Work in my laboratory is directed at the role of tissue-derived factors during development or following either disease or nerve injury on primary afferent neurons as a model system. Sensory neurons are unique in elaborating a peripheral axon that regenerates readily after injury and a central axon projecting in the spinal cord that does not. This work is directly relevant to both the major NINDS goal of axon regeneration and the major goal of chronic pain control following injury or disease by multiple institutes including NINDS, NIDA, NIDDK, and NCI.

As PI or co-Investigator on both intramural and extramural grants, my laboratory has laid the much of the groundwork for the role of chemokine/receptors in the neuropathic pain field. My laboratory is now making inroads on the role of HMGB1 in preclinical and clinical trauma-associated inflammatory events. Additional work is focused on the off-target effects of opioids in the setting of chronic pain. This work may be instrumental in the discovery of new therapeutics in the clinic.

Search for Dr. White on PubMed

Publications for the last five years: 

Abbadie, C., Bhangoo, S., De Koninck, Y., Malcangio, M., Melik-Parsadaniantz, S., White, F. A., 2009. Chemokines and pain mechanisms. Brain Res Rev 60, 125-134.

Zhang, H., Mei, X., Zhang, P., Ma, C., White, F. A., Donnelly, D. F., Lamotte, R. H., 2009. Altered functional properties of satellite glial cells in compressed spinal ganglia. Glia 57, 1588-1599.

White, F. A., Feldman, P., Miller, R. J., 2009. Chemokine signaling and the management of neuropathic pain. Mol Interv 9, 188-195.

Miller, R. J., Jung, H., Bhangoo, S. K., White, F. A., 2009. Cytokine and chemokine regulation of sensory neuron function. Handb Exp Pharmacol, 417-449.

Jung, H., Bhangoo, S., Banisadr, G., Freitag, C., Ren, D., White, F. A., Miller, R. J., 2009. Visualization of chemokine receptor activation in transgenic mice reveals peripheral activation of CCR2 receptors in states of neuropathic pain. J Neurosci 29, 8051-8062.

Bhangoo, S. K., Ripsch, M. S., Buchanan, D. J., Miller, R. J., White, F. A., 2009. Increased chemokine signaling in a model of HIV1-associated peripheral neuropathy. Mol Pain 5, 48.

White, F. A., Miller, R. J., 2010. Insights into the regulation of chemokine receptors by molecular signaling pathways: functional roles in neuropathic pain. Brain Behav Immun 24, 859-865.

Wilson, S. M., Brittain, J. M., Piekarz, A. D., Ballard, C. J., Ripsch, M. S., Cummins, T. R., Hurley, J. H., Khanna, M., Hammes, N. M., Samuels, B. C., White, F. A., Khanna, R., 2011. Further insights into the antinociceptive potential of a peptide disrupting the N-type calcium channel-CRMP-2 signaling complex. Channels (Austin) 5, 449-456.

Wang, Y., Wilson, S. M., Brittain, J. M., Ripsch, M. S., Salome, C., Park, K. D., White, F. A., Khanna, R., Kohn, H., 2011. Merging Structural Motifs of Functionalized Amino Acids and alpha-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-gated Sodium Channels and in the Treatment of Neuropathic Pain. ACS Chem Neurosci 2, 317-322.

Brittain, J. M., Chen, L., Wilson, S. M., Brustovetsky, T., Gao, X., Ashpole, N. M., Molosh, A. I., You, H., Hudmon, A., Shekhar, A., White, F. A., Zamponi, G. W., Brustovetsky, N., Chen, J., Khanna, R., 2011a. Neuroprotection against traumatic brain injury by a peptide derived from the collapsin response mediator protein 2 (CRMP2). J Biol Chem 286, 37778-37792.

Brittain, J. M., Duarte, D. B., Wilson, S. M., Zhu, W., Ballard, C., Johnson, P. L., Liu, N., Xiong, W., Ripsch, M. S., Wang, Y., Fehrenbacher, J. C., Fitz, S. D., Khanna, M., Park, C. K., Schmutzler, B. S., Cheon, B. M., Due, M. R., Brustovetsky, T., Ashpole, N. M., Hudmon, A., Meroueh, S. O., Hingtgen, C. M., Brustovetsky, N., Ji, R. R., Hurley, J. H., Jin, X., Shekhar, A., Xu, X. M., Oxford, G. S., Vasko, M. R., White, F. A., Khanna, R., 2011b. Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca(2)(+) channel complex. Nat Med 17, 822-829.

Wilson, N. M., Jung, H., Ripsch, M. S., Miller, R. J., White, F. A., 2011. CXCR4 signaling mediates morphine-induced tactile hyperalgesia. Brain Behav Immun 25, 565-573.

Foster, R., Jung, J., Farooq, A., McClung, C., Ripsch, M. S., Fitzgerald, M. P., White, F. A., 2011. Sciatic nerve injury induces functional pro-nociceptive chemokine receptors in bladder-associated primary afferent neurons in the rat. Neuroscience 183, 230-237.

Ripsch, M. S., Ballard, C. J., Khanna, M., Hurley, J. H., White, F. A., Khanna, R., 2012. A peptide uncoupling CRMP-2 from the presynaptic Ca(2+) channel complex demonstrates efficacy in animal models of migraine and AIDS therapy-induced neuropathy. Transl Neurosci 3, 1-8.

Wilson, S. M., Schmutzler, B. S., Brittain, J. M., Dustrude, E. T., Ripsch, M. S., Pellman, J. J., Yeum, T. S., Hurley, J. H., Hingtgen, C. M., White, F. A., Khanna, R., 2012. Inhibition of transmitter release and attenuation of anti-retroviral-associated and tibial nerve injury-related painful peripheral neuropathy by novel synthetic Ca2+ channel peptides. J Biol Chem 287, 35065-35077.

Deng, L., Guindon, J., Vemuri, V. K., Thakur, G. A., White, F. A., Makriyannis, A., Hohmann, A. G., 2012. The maintenance of cisplatin- and paclitaxel-induced mechanical and cold allodynia is suppressed by cannabinoid CB(2) receptor activation and independent of CXCR4 signaling in models of chemotherapy-induced peripheral neuropathy. Mol Pain 8, 71.

King, A. M., Yang, X. F., Wang, Y., Dustrude, E. T., Barbosa, C., Due, M. R., Piekarz, A. D., Wilson, S. M., White, F. A., Salome, C., Cummins, T. R., Khanna, R., Kohn, H., 2012. Identification of the benzyloxyphenyl pharmacophore: a structural unit that promotes sodium channel slow inactivation. ACS Chem Neurosci 3, 1037-1049.

Piekarz, A. D., Due, M. R., Khanna, M., Wang, B., Ripsch, M. S., Wang, R., Meroueh, S. O., Vasko, M. R., White, F. A., Khanna, R., 2012. CRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy. Mol Pain 8, 54.

Due, M. R., Piekarz, A. D., Wilson, N., Feldman, P., Ripsch, M. S., Chavez, S., Yin, H., Khanna, R., White, F. A., 2012. Neuroexcitatory effects of morphine-3-glucuronide are dependent on Toll-like receptor 4 signaling. J Neuroinflammation 9, 200.

Feldman, P., Due, M. R., Ripsch, M. S., Khanna, R., White, F. A., 2012. The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain. J Neuroinflammation 9, 180.

Ju, W., Li, Q., Allette, Y. M., Ripsch, M. S., White, F. A., Khanna, R., 2013. Suppression of pain-related behavior in two distinct rodent models of peripheral neuropathy by a homopolyarginine-conjugated CRMP2 peptide. J Neurochem 124, 869-879.

Polcari, A. J., Farooq, A. V., Woods, M. E., Ripsch, M. S., Picken, M., Turk, T. M., White, F. A., 2013. Effect of the phosphodiesterase-5 inhibitor zaprinast on ischemia-reperfusion injury in rats. J Endourol 27, 338-342.

Allette, Y. M., Due, M. R., Wilson, S. M., Feldman, P., Ripsch, M. S., Khanna, R., White, F. A., 2014. Identification of a functional interaction of HMGB1 with Receptor for Advanced Glycation End-products in a model of neuropathic pain. Brain Behav Immun. 2014 Jul 8. pii: S0889-1591(14)00364-X. doi: 10.1016/j.bbi.2014.06.199.

Due, M. R., Park, J., Zheng, L., Walls, M., Allette, Y. M., Shi, R.*, White, F. A.* 2014. Acrolein involvement in sensory and behavioral hypersensitivity following spinal cord injury in the rat. J Neurochem 128, 776-786.

Due, M.R., Yang, X.F., Allette, Y.M., Randolph, A.L., Ripsch, M.R., Dustrude ,E.T., Wilson, S.M., Khanna, R., White, F.A. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain.  PLoS1, in press, 2014. 

Weber DJ, Gracon ASA, Ripsch MS, Fisher AJ, Allette YM, Cheon BM, Kim YS, Pandya PH, Brown KM, Riley AA, McCarthy BP, Territo P, Hutchins GD, Sandusky GE, Broxmeyer HE, Wilkes DS*, White FA*. The Role of the HMGB1-RAGE Inflammatory Pathway in Traumatic Brain Injury-induced Pulmonary Dysfunction in the Setting of Lung Transplantation. Science Translational Medicine, in press, 2014. 

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