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Stanley                        Halvorsen

Stanley W. Halvorsen PhD

Department of Pharmacology and Toxicology

Associate Professor

Specialty/Research Focus

Molecular and Cellular Biology; Neurodegenerative disorders; Signal Transduction; Toxicology and Xenobiotics; Transcription and Translation

 
Professional Summary:

My lab studies the receptor signaling mechanisms for a family of neurotrophic factors that includes ciliary neurotrophic factor (CNTF), leptin, interferon gamma, and cardiotrophin-1.  These factors use the Jak/STAT pathway to regulate neuronal survival, development and response to trauma. Our interests are in how activity of the receptors and their pathway components are regulated.  Currently this has focused on the impact of cellular oxidative stress on the inhibition of Jak tyrosine kinase activity. Increases in oxidative stress in neurons result in the blockade of not only CNTF family factor effects, but of many other cytokines that also use the Jak/STAT pathway for signaling such as interferons and interleukins. Non-nerve cells appear resistant to these effects of oxidative stress.

Ongoing projects include testing the theory that environmental contaminants known to increase oxidative stress in cells may promote neurodegenerative diseases by inhibiting growth factor signaling.  We have been studying the effects of certain heavy metals (cadmium & mercury) and pesticides (e.g. rotenone) on nerve cells in culture to determine the molecular basis for Jak inhibition.

Another examines a possible role of oxidative stress in obesity.  This study tests the hypothesis that the loss of the ability of the hormone leptin to regulate metabolism and appetite during obesity is a result of oxidative reactions that inhibit Jak-mediated signaling in the hypothalamus and other brain regions.

Education and Training:
  • Postdoctoral Fellow, Neurobiology, Univ. California - San Diego (1989)
  • PhD, Pharmacology, University of Washington (1984)
  • BPharm, Pharmacy, Washington State University, Cum Laude (1976)
Employment:
  • Associate Professor, Pharmacology and Toxicology, State University of New York at Buffalo (2000-present)
  • Assistant/Research Associate Professor, Biochemical Pharmacology, State University of New York at Buffalo (1990–2000)
  • Assistant Research Biologist, University of California-San Diego (1989–1990)
  • Postdoctoral Fellow, Department of Biology, University of California-San Diego (1984–1989)
  • Predoctoral Trainee, University of Washington (1979–1984)
  • Director of Pharmacy Services, U.S.P.H.S. Outpatient Clinic (1977–1979)
  • Hospital Pharmacy Resident, U.S. Public Health Service Hospital (1976–1977)

Research Expertise:
  • Cell Biology: Intracellular trafficking of STATs; nuclear translocation; oxidative stress; mitochondria dysfunction;
  • Molecular Neurobiology: Signaling mechanisms; transciptional regulation; immediate early genes; Ach esterase;
  • Molecular Signaling and Signal Transduction: Jak/STAT signaling; MAP kinase; ERK; Oxidative stress
  • Nerve and Growth Factors: ciliary neurotrophic factor; interferons; interleukins; neurodegenerative diseases
  • Neuropharmacology: Synaptic development; cholinergic synapses; neurotrophic factor effects; cholinergic differentiation
  • Oxidative stress: Impact of oxidative stress and free radicals on signal transduction and disease in the nervous system; mitochondria
  • Receptor Pharmacology: CNTF receptors; Jak/STAT coupled receptors; Nicotinic acetylcholine receptors; gp130 cytokine receptors ;
Grants and Sponsored Research:
  • CNTF Receptors on Neurons
    NIH-NINDS
    Role: Principal Investigator
    $526,134

Evaluative Studies and Case Reports:
Journal Articles:
  • Monroe RK, Halvorsen SW, Halvorsen S. Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption. Neurotoxicology. 2009; 30(4).
  • Monroe RK, Halvorsen SW,. Mercury Abolishes Neurotrophic Factor-Stimulated Jak-STAT Signaling in Nerve Cells by Oxidative Stress. Toxicol Sci. 2006; 94(1).
  • Monroe RK, Halvorsen SW,. Cadmium blocks receptor-mediated Jak/STAT signaling in neurons by oxidative stress. Free Radic Biol Med. 2006; 41(3).
  • Kaur N, Lu B, Monroe RK, Ward SM, Halvorsen SW,. Inducers of oxidative stress block ciliary neurotrophic factor activation of Jak/STAT signaling in neurons. J Neurochem. 2005; 92(6).
  • Kaur N, Kim IJ, Higgins D, Halvorsen SW. Induction of an interferon-gamma Stat3 response in nerve cells by pre-treatment with gp130 cytokines.. J Neurochem. 2003; 87(2).
  • Jiao J, Kaur N, Lu B, Reeves SA, Halvorsen SW. Initiation and maintenance of CNTF-Jak/STAT signaling in neurons is blocked by protein tyrosine phosphatase inhibitors.. Brain Res Mol Brain Res. 2003; 116(1-2).
  • Kaur, N., Wohlhueter, A.L., Halvorsen S. Activation and inactivation of signal transducers and activators of transcription by ciliary neurotrophic factor in neuroblastoma cells. Cellular Signalling. 2002; 14.
  • Malek RL, Halvorsen SW. Ciliary neurotrophic factor and phorbol ester each decrease selected STAT3 pools in neuroblastoma cells by proteasome-dependent mechanisms.. Cytokine. 1999; 11(3).
  • Wang X, Halvorsen SW. Reciprocal regulation of ciliary neurotrophic factor receptors and acetylcholine receptors during synaptogenesis in embryonic chick atria.. J Neurosci. 1998; 18(18).
  • Wang X, Halvorsen SW. Retinoic acid up-regulates ciliary neurotrophic factor receptors in cultured chick neurons and cardiomyocytes.. Neurosci Lett. 1998; 240(1).
  • Thomas SL, Chmelar RS, Lu C, Halvorsen SW, Nathanson NM. Tissue-specific regulation of G-protein-coupled inwardly rectifying K+ channel expression by muscarinic receptor activation in ovo.. J Biol Chem. 1997; 272(47).
  • Wishingrad MA, Koshlukova S, Halvorsen SW. Ciliary neurotrophic factor stimulates the phosphorylation of two forms of STAT3 in chick ciliary ganglion neurons.. J Biol Chem. 1997; 272(32).
  • Lu C, Halvorsen SW. Channel activators regulate ATP-sensitive potassium channel (KIR6.1) expression in chick cardiomyocytes.. FEBS Lett. 1997; 412(1).
  • Malek RL, Halvorsen SW. Opposing regulation of ciliary neurotrophic factor receptors on neuroblastoma cells by distinct differentiating agents.. J Neurobiol. 1997; 32(1).
  • Koshlukova S, Finn TP, Nishi R, Halvorsen SW. Identification of functional receptors for ciliary neurotrophic factor on chick ciliary ganglion neurons.. Neuroscience. 1996; 72(3).
  • Halvorsen SW, Malek R, Wang X, Jiang N. Ciliary neurotrophic factor regulates nicotinic acetylcholine receptors on human neuroblastoma cells.. Neuropharmacology. 1996; 35(3).
  • Halvorsen SW, Jiang N, Malek R. Regulation of nicotinic acetylcholine receptors on human neuroblastoma cells during differentiation.. Biochem Pharmacol. 1995; 50(10).
  • Lu C, Hegde P, Halvorsen SW. Regulation of glibenclamide receptors in cultured chick cardiomyocytes.. Pharmacol Res. 1995; 32(3).
  • Halvorsen SW, Schmid HA, McEachern AE, Berg DK. Regulation of acetylcholine receptors on chick ciliary ganglion neurons by components from the synaptic target tissue.. J Neurosci. 1991; 11(7).
  • Vijayaraghavan S, Schmid HA, Halvorsen SW, Berg DK. Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit.. J Neurosci. 1990; 10(10).
  • Halvorsen SW, Berg DK. Subunit composition of nicotinic acetylcholine receptors from chick ciliary ganglia.. J Neurosci. 1990; 10(6).
  • Schoepfer R, Halvorsen SW, Conroy WG, Whiting P, Lindstrom J. Antisera against an acetylcholine receptor alpha 3 fusion protein bind to ganglionic but not to brain nicotinic acetylcholine receptors.. FEBS Lett. 1989; 257(2).
  • Halvorsen SW, Berg DK. Specific down-regulation of the alpha-bungarotoxin binding component on chick autonomic neurons by ciliary neuronotrophic factor.. J Neurosci. 1989; 9(10).
  • Halvorsen SW, Berg DK. Affinity labeling of neuronal acetylcholine receptor subunits with an alpha-neurotoxin that blocks receptor function.. J Neurosci. 1987; 7(8).
  • Martin JM, Subers EM, Halvorsen SW, Nathanson NM. Functional and physical properties of chick atrial and ventricular GTP-binding proteins: relationship to muscarinic acetylcholine receptor-mediated responses.. J Pharmacol Exp Ther. 1987; 240(2).
  • Halvorsen SW, Berg DK. Identification of a nicotinic acetylcholine receptor on neurons using an alpha-neurotoxin that blocks receptor function.. J Neurosci. 1986; 6(11).
  • Halvorsen SW, Nathanson NM. Ontogenesis of physiological responsiveness and guanine nucleotide sensitivity of cardiac muscarinic receptors during chick embryonic development.. Biochemistry. 1984; 23(24).
  • Nathanson NM, Holttum J, Hunter DD, Halvorsen SW. Partial agonist activity of oxotremorine at muscarinic acetylcholine receptors in the embryonic chick heart.. J Pharmacol Exp Ther. 1984; 229(2).
  • Halvorsen SW, Nathanson NM. In vivo regulation of muscarinic acetylcholine receptor number and function in embryonic chick heart.. J Biol Chem. 1981; 256(15).
See all (19 more)
Books and Book Chapters:
  • Halvorsen S Kaur, N. CNTF and Related Neurokines. Handbook of Neurochemistry and Molecular Neurobiology, 3rd Edition,. 2006.
  • Koshlukova S Halvorsen S. Chick Ciliary Ganglion Neurons. The Neuron in Tissue Culture. 1999.

Professional Memberships:
  • American Association of Colleges of Pharmacy; Organization for facuty in pharmacy profession (1990–present)
  • American Association for the Advancement of Science (1989–present)
  • Society for Neuroscience (1985–present)
Service Activities:
  • Pharmacology and Toxicology, Jacobs School of Medicine & Biomedical Sciences Curriculum; Member (2009)
  • Jacobs School of Medicine & Biomedical Sciences Apppointment, Promotions,Tenure & Privileges; Member (2008)
  • Pharmacology and Toxicology, Jacobs School of Medicine & Biomedical Sciences Proposition Exam; Chair (2004)
  • Jacobs School of Medicine & Biomedical Sciences Research Promotions; Chair (2003–2004)
  • Jacobs School of Medicine & Biomedical Sciences Research Promotions; Member (2002–2004)
  • Director of Graduate Admissions; Director of admissions for the IGPBS Graduate Programs in the Biomedical Sciences; Director (2004–2009)

School News:
In the Media:

Clinical Specialties:
Clinical Offices:
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Contact Information

207 Sherman Hall
Buffalo, NY 14214
Phone: (716) 829-2651
Email: stanh@buffalo.edu


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