Chair and Van Vleet Professor
Room 115 Crowe Research Building
(901) 448-6001
FAX (901) 448-7206
bsharp@utmem.edu
EDUCATION
1971 B.A. State University of New York-Stony Brook
1975 M.D. University of Cincinnati, College of Medicine
RESEARCH INTERESTS
My reseach program has dual foci involving (1) the basic neurochemistry
and molecular neurobiology of nicotine and (2) cellular and biochemical
approaches to understand the action of opioid peptides on the immune system.
The nicotine research uses in vivo microdialysis coupled with measurements
of biogenic amines and excitatory amino acids to understand both the neurochemical
basis for addiction to nicotine and the beneficial therapeutic effects
of nicotinic agonists on hypothalamic and hippocampal function. In many
of these studies, nicotine is delivered acutely through intra-jugular
catheters and cannulae that are chronically implanted in specific CNS
sites. Animals also learn to self-administer nicotine through operant
conditioning that mimics human smoking. In vivo microdialysis in these
self-administering animals permits analysis of changes in brain neurochemistry
and direct correlation of these with drug-dependent behavior. Using RT-PCR,
analyses are made of specific gene expression in micropunched areas of
brain. Similarly, in situ hybridization analyses are used to characterize
the effects of nicotine self-administration on short and longterm changes
in CNS gene expression.
My research on opioid immunobiology seeks to understand the cellular and
molecular basis for the modulatory effects of opiates and opioid peptides
on lymphocytes, specifically T-cells. Using fluorescence flow cytometry
and RT-PCR, we are characterizing the expression of delta opioid receptors
on specific subsets of T lymphocytes. Biochemical and immunological approaches
(e.g.immunoprecipitation, Western immunoblotting, receptor binding) are
used to elucidate the signal transduction pathways that mediate the anti-proliferative
actions of delta opioid receptors on T-cells. Our current focus is on
the role of mitogen-activated protein kinases (MAPKs) in opioid signaling,
as this pertains to the effects of opioids on MAPK-dependent interleukin-2
production.
SELECTED PUBLICATIONS
Wang F, Chen H, Sharp BM. Neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self-administration and after extinction in rats. J Neurochem. 2008 Jul;106(2):943-56. Epub 2008 May 3. PMID: 18466321
Yu G, Chen H, Zhao W, Matta SG, Sharp BM. Nicotine self-administration differentially regulates hypothalamic corticotropin-releasing factor and arginine vasopressin mRNAs and facilitates stress-induced neuronal activation. J Neurosci. 2008 Mar 12;28(11):2773-82. PMID: 18337407
Shahabi NA, McAllen K, Sharp BM. Stromal cell-derived factor 1-alpha (SDF)-induced human T cell chemotaxis becomes phosphoinositide 3-kinase (PI3K)-independent: role of PKC-theta. J Leukoc Biol. 2008 Mar;83(3):663-71. Epub 2007 Nov 30. PMID: 18055570
Chen H, Fu Y, Sharp BM. Chronic nicotine self-administration augments hypothalamic-pituitary-adrenal responses to mild acute stress. Neuropsychopharmacology. 2008 Mar;33(4):721-30. Epub 2007 Jun 6. PMID: 17551542
Zhao R, Chen H, Sharp BM. Nicotine-induced norepinephrine release in hypothalamic paraventricular nucleus and amygdala is mediated by N-methyl-D-aspartate receptors and nitric oxide in the nucleus tractus solitarius. J Pharmacol Exp Ther. 2007 Feb;320(2):837-44. Epub 2006 Nov 8. PMID: 17093131
Chen H, Matta SG, Sharp BM. Acquisition of nicotine self-administration in adolescent rats given prolonged access to the drug. Neuropsychopharmacology. 2007 Mar;32(3):700-9. Epub 2006 Jun 14. PMID: 16794562
Sharp B, Yatsula M, Fu Y. Effects of galantamine, a nicotinic allosteric potentiating ligand, on nicotine-induced catecholamine release in hippocampus and nucleus accumbens of rats. J Pharmacol Exp Ther. 2004 Feb 9
Kane VB, Fu Y, Matta SG, Sharp BM. Gestational nicotine exposure attenuates nicotine-stimulated dopamine release in the nucleus accumbens shell of adolescent Lewis rats. J Pharmacol Exp Ther. 2004 Feb;308(2):521-8.
Parker SL, Fu Y, McAllen K, Luo J, McIntosh JM, Lindstrom JM, Sharp BM. Up-Regulation of Brain Nicotinic Acetylcholine Receptors in the Rat during Long-Term Self-Administration of Nicotine: Disproportionate Increase of the {alpha}6 Subunit. Mol Pharmacol. 2004 Mar;65(3):611-622.
Brower, VG, Fu Y, Matta SG and Sharp BM. Rat strain differences in nicotine
self-administration using an unlimited access paradigm. Brain Research
2002, 930(1-2):12-20.
Chen H and Sharp BM. OLIZ, a suite of Perl scripts that assist in the design
of microarrays using 50mer oligonucleotides from the 3' untranslated region.
BMC Bioinformatics 2002, 3: 27 (available at: http://www.biomedcentral.com/1471-2105/3/27)
Sharp, BM, McAllen K, Gekker G, Shahabi NA and Peterson PK. Immunofluorescence
detection of delta opioid receptors (DOR) on human peripheral blood CD4+
T-cells and DOR-dependent suppression of HIV-1 expression. J. Immunol.
2001, 167:1097-1102.
Fu Y, Matta SG, Brower VG and Sharp BM. Norepinephrine secretion in the hypothalamic
paraventricular nucleus of rats during unlimited access to self-administered
nicotine: an in vivo microdialysis study. J. Neuroscience 2001, 21(22):8979-8989.
Fu Y, Matta SG, Gao W, Brower V and Sharp BM. Systemic nicotine stimulates
dopamine release in the nucleus accumbens: re-evaluation of the role
of N-methyl-D-aspartate receptors in the ventral tegmental area. J.
Pharm. Exp.Ther. 2000; 294:458-465.
Fu Y, Matta SG, Gao W and Sharp BM. Local alpha-bungarotoxin-sensitive
nicotinic receptors in the nucleus accumbens modulate nicotine-stimulated
dopamine secretion in vivo. Neuroscience 2000, 101(2):369-375.
Shahabi, NA, McAllen K, Matta SG and Sharp BM. Expression of delta
opioid receptors by splenocytes from SEB-treated mice and effects on
phosphorylation of MAP kinase. Cellular Immunol. 2000, 205(2):84-93.