Stanley W. Halvorsen PhD
Stanley W. Halvorsen
PhD
Associate Professor
Department of Pharmacology and Toxicology
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Molecular and Cellular Biology; Neurodegenerative disorders; Signal Transduction; Toxicology; 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:
- Other, Neurobiology, Univ. California - San Diego (1989)
- PhD, Pharmacology, University of Washington (1984)
- Residency, Hospital Pharmacy, US Public Health Service Hospital Staten Island, NY (1977)
- BPharm, Pharmacy, Washington State University, Cum Laude (1976)
Employment:
- Executive Director, Regulatory Support, Research & Economic Development, University at Buffalo (2019-present)
- Associate Professor, Pharmacology and Toxicology, State University of New York at Buffalo Jacobs School of Medicine & Biomedical Sciences (2000-present)
- Assistant/Research Associate Professor, Biochemical Pharmacology, State University of New York at Buffalo School of Pharmacy (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, US Public Health Service (1977–1979)
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
Journal Articles:
- Sternberg Z, Podolsky R, Nir A, Yu J, Nir R, Halvorsen SW, Chadha K, Quinn JF, Kaye J, Kolb C. (2019) Increased free prostate specific antigen serum levels in Alzheimer's disease, correlation with Cognitive Decline. J Neurol Sci (May), 400: 188-193.
- Monroe RK, Halvorsen SW, Halvorsen S. (2009) Environmental toxicants inhibit neuronal Jak tyrosine kinase by mitochondrial disruption. Neurotoxicology (Jul), 30(4): 589-598.
- Monroe RK, Halvorsen SW,. (2006) Mercury Abolishes Neurotrophic Factor-Stimulated Jak-STAT Signaling in Nerve Cells by Oxidative Stress. Toxicol Sci (Nov), 94(1): 129-138.
- Monroe RK, Halvorsen SW,. (2006) Cadmium blocks receptor-mediated Jak/STAT signaling in neurons by oxidative stress. Free Radic Biol Med (Aug), 41(3): 493-502.
- Kaur N, Lu B, Monroe RK, Ward SM, Halvorsen SW,. (2005) Inducers of oxidative stress block ciliary neurotrophic factor activation of Jak/STAT signaling in neurons. J Neurochem (Mar), 92(6): 1521-1530.
- Kapoor R, Kaur N, Nishanth ET, Halvorsen SW, Bergey EJ, Prasad PN, Halvorsen S. (2004) Detection of trophic factor activated signaling molecules in cells by a compact fiber-optic sensor. Biosens Bioelectron (Sep), 20(2): 345-349.
- Kaur N, Kim IJ, Higgins D, Halvorsen SW. (2003) Induction of an interferon-gamma Stat3 response in nerve cells by pre-treatment with gp130 cytokines. J Neurochem (Oct), 87(2): 437-447.
- Jiao J, Kaur N, Lu B, Reeves SA, Halvorsen SW. (2003) Initiation and maintenance of CNTF-Jak/STAT signaling in neurons is blocked by protein tyrosine phosphatase inhibitors. Brain research. Molecular brain research (Aug), 116(1-2): 135-46.
- Kaur N, Wohlhueter AL, Halvorsen SW. (2002) Activation and inactivation of signal transducers and activators of transcription by ciliary neurotrophic factor in neuroblastoma cells. Cellular signalling (May), 14(5): 419-29.
- Halvorsen S. (2001) Book Review of: The RBI Handbook of Receptor Classification and Signal Transduction. Pharmaceutical News (Jan), 8: 60-61.
- Halvorsen S. (2000) Book Review of: Structure-function Analysis of G-Protein-Coupled Receptors. Pharmaceutical News (Jan), 7: 45.
- Malek RL, Halvorsen SW. (1999) Ciliary neurotrophic factor and phorbol ester each decrease selected STAT3 pools in neuroblastoma cells by proteasome-dependent mechanisms. Cytokine (Mar), 11(3): 192-199.
- Halvorsen S. (1999) Book Review of: Identification and Expression of G-Protein-Coupled Receptors. Pharmaceutical News (Jan), 6: 29.
- Halvorsen S. (1999) Book Review of: The RBI Handbook of Receptor Classification and Signal Transduction. Pharmaceutical News (Jan), 6: 27-28.
- Wang X, Halvorsen SW. (1998) Reciprocal regulation of ciliary neurotrophic factor receptors and acetylcholine receptors during synaptogenesis in embryonic chick atria. The Journal of neuroscience : the official journal of the Society for Neuroscience (Sep), 18(18): 7372-80. doi:10.1523/JNEUROSCI.18-18-07372.1998
- Wang X, Halvorsen SW. (1998) Retinoic acid up-regulates ciliary neurotrophic factor receptors in cultured chick neurons and cardiomyocytes. Neurosci Lett (Jan), 240(1): 9-12.
- Thomas SL, Chmelar RS, Lu C, Halvorsen SW, Nathanson NM. (1997) Tissue-specific regulation of G-protein-coupled inwardly rectifying K+ channel expression by muscarinic receptor activation in ovo. J Biol Chem (Nov), 272(47): 29958-29962.
- Wishingrad MA, Koshlukova S, Halvorsen SW. (1997) Ciliary neurotrophic factor stimulates the phosphorylation of two forms of STAT3 in chick ciliary ganglion neurons. J Biol Chem (Aug), 272(32): 19752-19757.
- Lu C, Halvorsen SW. (1997) Channel activators regulate ATP-sensitive potassium channel (KIR6.1) expression in chick cardiomyocytes. FEBS Lett (Jul), 412(1): 121-125.
- Malek RL, Halvorsen SW. (1997) Opposing regulation of ciliary neurotrophic factor receptors on neuroblastoma cells by distinct differentiating agents. J Neurobiol (Jan), 32(1): 81-94.
- Koshlukova S, Finn TP, Nishi R, Halvorsen SW. (1996) Identification of functional receptors for ciliary neurotrophic factor on chick ciliary ganglion neurons. Neuroscience (Jun), 72(3): 821-832.
- Halvorsen SW, Malek R, Wang X, Jiang N. (1996) Ciliary neurotrophic factor regulates nicotinic acetylcholine receptors on human neuroblastoma cells. Neuropharmacology (Mar), 35(3): 257-265.
- Halvorsen SW, Jiang N, Malek R. (1995) Regulation of nicotinic acetylcholine receptors on human neuroblastoma cells during differentiation. Biochem Pharmacol (Nov), 50(10): 1665-1671.
- Lu C, Hegde P, Halvorsen SW. (1995) Regulation of glibenclamide receptors in cultured chick cardiomyocytes. Pharmacol Res (Sep), 32(3): 149-153.
- Halvorsen SW, Schmid HA, McEachern AE, Berg DK. (1991) Regulation of acetylcholine receptors on chick ciliary ganglion neurons by components from the synaptic target tissue. The Journal of neuroscience : the official journal of the Society for Neuroscience (Jul), 11(7): 2177-86. doi:10.1523/JNEUROSCI.11-07-02177.1991
- Vijayaraghavan S, Schmid HA, Halvorsen SW, Berg DK. (1990) Cyclic AMP-dependent phosphorylation of a neuronal acetylcholine receptor alpha-type subunit. The Journal of neuroscience : the official journal of the Society for Neuroscience (Oct), 10(10): 3255-62. doi:10.1523/JNEUROSCI.10-10-03255.1990
- Halvorsen SW, Berg DK. (1990) Subunit composition of nicotinic acetylcholine receptors from chick ciliary ganglia. The Journal of neuroscience : the official journal of the Society for Neuroscience (Jun), 10(6): 1711-8. doi:10.1523/JNEUROSCI.10-06-01711.1990
- Schoepfer R, Halvorsen SW, Conroy WG, Whiting P, Lindstrom J. (1989) Antisera against an acetylcholine receptor alpha 3 fusion protein bind to ganglionic but not to brain nicotinic acetylcholine receptors. FEBS Lett (Nov), 257(2): 393-399.
- Halvorsen SW, Berg DK. (1989) Specific down-regulation of the alpha-bungarotoxin binding component on chick autonomic neurons by ciliary neuronotrophic factor. The Journal of neuroscience : the official journal of the Society for Neuroscience (Oct), 9(10): 3673-80. doi:10.1523/JNEUROSCI.09-10-03673.1989
- Berg DK, Boyd RT, Halvorsen SW, Higgins LS, Jacob MH, Margiotta JF. (1989) Regulating the number and function of neuronal acetylcholine receptors. Trends Neurosci (Jan), 12(1): 16-21.
- Berg DK, Halvorsen SW. (1988) Acetylcholine receptor. Genes encoding nicotinic receptor subtypes on neurons. Nature (Aug), 334(6181): 384-385.
- Halvorsen SW, Berg DK. (1987) Affinity labeling of neuronal acetylcholine receptor subunits with an alpha-neurotoxin that blocks receptor function. The Journal of neuroscience : the official journal of the Society for Neuroscience (Aug), 7(8): 2547-55.
- Martin JM, Subers EM, Halvorsen SW, Nathanson NM. (1987) Functional and physical properties of chick atrial and ventricular GTP-binding proteins: relationship to muscarinic acetylcholine receptor-mediated responses. J Pharmacol Exp Ther (Feb), 240(2): 683-688.
- Halvorsen SW, Berg DK. (1986) Identification of a nicotinic acetylcholine receptor on neurons using an alpha-neurotoxin that blocks receptor function. The Journal of neuroscience : the official journal of the Society for Neuroscience (Nov), 6(11): 3405-12. doi:10.1523/JNEUROSCI.06-11-03405.1986
- Halvorsen SW, Nathanson NM. (1984) Ontogenesis of physiological responsiveness and guanine nucleotide sensitivity of cardiac muscarinic receptors during chick embryonic development. Biochemistry (Nov), 23(24): 5813-5821.
- Nathanson NM, Holttum J, Hunter DD, Halvorsen SW. (1984) Partial agonist activity of oxotremorine at muscarinic acetylcholine receptors in the embryonic chick heart. J Pharmacol Exp Ther (May), 229(2): 455-458.
- Halvorsen SW, Engel B, Hunter DD, Nathanson NM. (1983) Development and regulation of cardiac muscarinic acetylcholine receptor number, function and guanyl nucleotide sensitivity. Advances in experimental medicine and biology (Jan), 161: 143-58.
- Halvorsen SW, Nathanson NM. (1981) In vivo regulation of muscarinic acetylcholine receptor number and function in embryonic chick heart. J Biol Chem (Aug), 256(15): 7941-7948.
Books and Book Chapters:
- Halvorsen S Kaur, N. (2006) CNTF and Related Neurokines. Springer Science.
- Koshlukova S Halvorsen S. (1999) The Neuron in Tissue Culture, International Brain Research Organization (IBRO) Handbook series: Methods in Neurosciences. In: Chick Ciliary Ganglion Neurons. John Wiley & Sons, 441-446.
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:
- Research Integrity Committee for University of Rochester; Outside Committee member (2021–2022)
- Institutional Biosafety Committee; Chair (2019–2022)
- Joint Stem Cell Oversight Committee; Co-Chair (2019–present)
- Radiation Safety Committee; Institutional Official (2019–present)
- Ad Hoc committee - Capstone/PMY405-6 (2019–2021)
- Curriculum; Member (2009–present)
- Departmental awards committee; Member (2009–2022)
- Appointment, Promotions,Tenure & Privileges; Member (2008–2014)
- Neuroscience Graduate Program Steering Committee; Member (2007–2020)
- Buffalo Chapter of Society for Neuroscience; Treasurer (2007–2022)
- Director of PhD Admissions for Medical School; IGPBS Graduate Admissions (2004–2009)
- IGPBS graduate program steering committee; Member (2004–2009)
- Proposition Exam coordinator for department; Chair (2004)
- Research Promotions; Chair (2003–2004)
- IRCAF Panel - Bio/Chem/Life Sciences L2 Grant Review Panel; Member (2003)
- Research Promotions; Member (2002–2004)
- Graduate Admissions; Co-Chair (2002–present)
- Center for Molecular Biology and Immunology (CAMBI); Co-Director (2000–2004)
- Graduate Affairs & Admissions for Molecular and Cell Biology Program (MCBP); Member (1994–2000)
- IACUC, subcommittee A; Member (1993–1995)
- ; Host family for international students and scholars (1992–2000)
- Chair of Graduate Affairs Committee and Director of Graduate Studies, Dept. Biochemical Pharmacology; Chair & Director (1991–2001)
- Pharmaceutical Sciences NIH Training Grant Executive Committee; Member (1991–1996)