Dr. Wayne Bowen earned his B.S. in chemistry from Morgan State College in 1974, and completed his Ph.D. in biochemistry and neurobiology at Cornell University in 1981. After postdoctoral studies at the National Institute of Mental Health (NIMH), he initially came to Brown University in 1983, as Assistant Professor of Biology in the Section of Biochemistry where he taught endocrinology, introductory biology, and biochemistry and did research on opioid and sigma receptors in the brain. Shortly after promotion to Associate Professor, he moved back to the NIH in 1991 to establish the Unit on Receptor Biochemistry and Pharmacology within the Laboratory of Medicinal Chemistry of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). He returned to Brown University in 2004 to take his current position as Professor of Biology in the Department of Molecular Pharmacology, Physiology & Biotechnology in the Division of Biology and Medicine. In 2007, he assumed the position as department chair and was named Upjohn Professor of Pharmacology in 2008.
Dr. Bowen is a nationally recognized leader in research on sigma receptors, membrane proteins found in tissues throughout the body and that are highly upregulated in cancer cells. He has shown that activation of sigma-2 receptors induces apoptotic cell death, and therefore they may serve as regulators of cell proliferation and survival. He is interested in signal transduction, particularly those pathways that lead to receptor-mediated cell death. Trained initially as a chemist, he maintains a strong interest and involvement in medicinal chemistry and drug design, particularly in relation to development of selective sigma receptor agonists and antagonists. He is exploring these compounds as potential anti-neoplastic, tumor diagnostic, and neuroprotective agents.
Dr. Bowen currently co-directs the medical school's pharmacology course, teaches in endocrinology and neuroscience courses for undergraduates, and co-directs the core pharmacology course for the Molecular Pharmacology and Physiology Graduate Program. Dr. Bowen is a member of the Society for Neuroscience, the International Brain Research Organization/World Federation of Neuroscientists, and the American Association for Cancer Research. He is the recipient of numerous awards and honors, and has performed service on NIMH and NIDA Study Sections. He served as president of the NIH Black Scientists Association in 2001. Dr. Bowen's research has been funded by NIDA, NINDS, NIDDK, the Rhode Island Science and Technology Advisory Council, and a Salomon Award from Brown University.
|Chou, Timothy, Jacobs, Michaela, Nicholson, Hilary, Bowen, Wayne D. "Abstract 1699: Differential aggregation rates and therapeutic response of pancreatic cancer cell lines to sigma-2 receptor activation in 3D culture." Cancer Research, vol. 75, no. 15 Supplement, 2015, pp. 1699-1699.|
|Nicholson, Hilary Elaine, Alsharif, Walid, McCurdy, Christopher R., Bowen, Wayne D. "Abstract 2440: Evaluation of structural changes in SN79-derived sigma-2 receptor modulators: effect on apoptotic efficacy in SK-N-SH neuroblastoma." Cancer Research, vol. 75, no. 15 Supplement, 2015, pp. 2440-2440.|
|Liu, Zongyi, Nicholson, Hilary E., Bowen, Wayne D. "Abstract 5428: Sigma-2 receptor-induced cell death: a novel approach to triple-negative breast cancer treatment." Cancer Research, vol. 75, no. 15 Supplement, 2015, pp. 5428-5428.|
|Nicholson, H., Comeau, A., Mesangeau, C., McCurdy, C. R., Bowen, W. D. "Characterization of CM572, a Selective Irreversible Partial Agonist of the Sigma-2 Receptor with Antitumor Activity." Journal of Pharmacology and Experimental Therapeutics, vol. 354, no. 2, 2015, pp. 203-212.|
|Nicholson, H., Mesangeau, C., McCurdy, C. R., Bowen, W. D. "Sigma-2 Receptors Play a Role in Cellular Metabolism: Stimulation of Glycolytic Hallmarks by CM764 in Human SK-N-SH Neuroblastoma." Journal of Pharmacology and Experimental Therapeutics, vol. 356, no. 2, 2015, pp. 434-445.|
|Nicholson, Hilary E., Chia, Pei Ling, Comeau, Anthony, Mesangeau, Christophe, McCurdy, Christopher, Bowen, Wayne D. "Abstract 3237: Characterization of CM-572 and CM-769: Novel irreversible modulators of sigma-2 receptor function." Cancer Research, vol. 74, no. 19 Supplement, 2014, pp. 3237-3237.|
|Nicholson, Hilary, Comeau, Anthony, Mesangeau, Christophe, McCurdy, Christopher R., Bowen, Wayne D. "Abstract 2242: Development of selective irreversible antagonists for sigma-2 receptors." Cancer Research, vol. 73, no. 8 Supplement, 2013, pp. 2242-2242.|
|Wanebo, Harold J., Cong, Cao, Shu, Li, Shrayer, David, Wan, Yeushung, Bowen, Wayne. "Abstract 600: Liposomal C6 ceramide appears to potentiate enhanced chemotoxicity of pancreatic cancer." Cancer Research, vol. 73, no. 8 Supplement, 2013, pp. 600-600.|
|Wanebo, H. J., Cao, C., Lu, S., Shrayer, D., Wan, Y., Bowen, W., Bowen, W. "Abstract B104: Liposomal C6 Ceramide appears to potentiate chemotoxicity of paclitaxel, gemcitabine and cetuximab against aggressive pancreatic cancer." Molecular Cancer Therapeutics, vol. 12, no. 11_Supplement, 2013, pp. B104-B104.|
|Wu, Chia-Hsuan, Cao, Cong, Kim, Jin Ho, Hsu, Chih-Hsun, Wanebo, Harold J., Bowen, Wayne D., Xu, Jimmy, Marshall, John. "Trojan-Horse Nanotube On-Command Intracellular Drug Delivery." Nano Letters, vol. 12, no. 11, 2012, pp. 5475-80.|
|Wei Z, Qi J, Dai Y, Bowen WD, Mousseau DD. "Haloperidol disrupts Akt signalling to reveal a phosphorylation-dependent regulation of pro-apoptotic Bcl-XS function." Cellular signalling, vol. 21, no. 1, 2009, pp. 161-8.|
|Liu Q, Bhat M, Bowen WD, Cheng J. "Signaling pathways from cannabinoid receptor-1 activation to inhibition of N-methyl-D-aspartic acid mediated calcium influx and neurotoxicity in dorsal root ganglion neurons." The Journal of pharmacology and experimental therapeutics, vol. 331, no. 3, 2009, pp. 1062-70.|
|Wu Z, Bowen WD. "Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells." Journal of Biological Chemistry, vol. 283, no. 42, 2008, pp. 28198-215.|
|Martin-Fardon R, Maurice T, Aujla H, Bowen WD, Weiss F. "Differential effects of sigma1 receptor blockade on self-administration and conditioned reinstatement motivated by cocaine vs natural reward." Neuropsychopharmacology, vol. 32, no. 9, 2007, pp. 1967-73.|
|Matsumoto RR, Gilmore DL, Pouw B, Bowen WD, Williams W, Kausar A, Coop A. "Novel analogs of the sigma receptor ligand BD1008 attenuate cocaine-induced toxicity in mice." European journal of pharmacology, vol. 492, no. 1, 2004, pp. 21-6.|
|Bowen, W. D. "Sigma receptors as novel target structures for cancer chemotherapeutics." Experimental Dermatology, vol. 13, no. 9, 2004, pp. 570-570.|
|Gebreselassie D, Bowen WD. "Sigma-2 receptors are specifically localized to lipid rafts in rat liver membranes." European journal of pharmacology, vol. 493, no. 1-3, 2004, pp. 19-28.|
|Matsumoto RR, Potelleret FH, Mack A, Pouw B, Zhang Y, Bowen WD. "Structure-activity comparison of YZ-069, a novel sigma ligand, and four analogs in receptor binding and behavioral studies." Pharmacology Biochemistry and Behavior, vol. 77, no. 4, 2004, pp. 775-81.|
|Romieu P, Meunier J, Garcia D, Zozime N, Martin-Fardon R, Bowen WD, Maurice T. "The sigma1 (sigma1) receptor activation is a key step for the reactivation of cocaine conditioned place preference by drug priming." Psychopharmacology, vol. 175, no. 2, 2004, pp. 154-62.|
|Foster A, Wu H, Chen W, Williams W, Bowen WD, Matsumoto RR, Coop A. "1,4-dibenzylpiperazines possess anticocaine activity." Bioorganic & Medicinal Chemistry Letters, vol. 13, no. 4, 2003, pp. 749-51.|
|Cao J, Kulkarni SS, Husbands SM, Bowen WD, Williams W, Kopajtic T, Katz JL, George C, Newman AH. "Dual probes for the dopamine transporter and sigma1 receptors: novel piperazinyl alkyl-bis(4'-fluorophenyl)amine analogues as potential cocaine-abuse therapeutic agents." Journal of medicinal chemistry, vol. 46, no. 13, 2003, pp. 2589-98.|
|Romieu P, Martin-Fardon R, Bowen WD, Maurice T. "Sigma 1 receptor-related neuroactive steroids modulate cocaine-induced reward." Journal of Neuroscience, vol. 23, no. 9, 2003, pp. 3572-6.|
|Matsumoto RR, McCracken KA, Pouw B, Zhang Y, Bowen WD. "Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides." Neuropharmacology, vol. 42, no. 8, 2002, pp. 1043-55.|
|Maeda DY, Williams W, Kim WE, Thatcher LN, Bowen WD, Coop A. "N-arylalkylpiperidines as high-affinity sigma-1 and sigma-2 receptor ligands: phenylpropylamines as potential leads for selective sigma-2 agents." Bioorganic & Medicinal Chemistry Letters, vol. 12, no. 3, 2002, pp. 497-500.|
|Crawford KW, Coop A, Bowen WD. "sigma(2) Receptors regulate changes in sphingolipid levels in breast tumor cells." European journal of pharmacology, vol. 443, no. 1-3, 2002, pp. 207-9.|
|Crawford KW, Bowen WD. "Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines." Cancer Research, vol. 62, no. 1, 2002, pp. 313-22.|
|Walker JM, Bowen WD, Patrick SL, Williams WE, Mascarella SW, Bai X, Carroll FI. "A comparison of (-)-deoxybenzomorphans devoid of opiate activity with their dextrorotatory phenolic counterparts suggests role of sigma 2 receptors in motor function." European journal of pharmacology, vol. 231, no. 1, 1993, pp. 61-8.|
|Hemstreet MK, Matsumoto RR, Bowen WD, Walker JM. "Sigma binding parameters in developing rats predict behavioral efficacy of a sigma ligand." Brain Research, vol. 627, no. 2, 1993, pp. 291-8.|
|Bowen WD, Tolentino PJ, Kirschner BN, Varghese P, de Costa BR, Rice KC. "Sigma receptors and signal transduction: negative modulation of signaling through phosphoinositide-linked receptor systems." NIDA research monograph, vol. 133, 1993, pp. 69-93.|
|Walker JM, Bowen WD, Goldstein SR, Roberts AH, Patrick SL, Hohmann AG, DeCosta B. "Autoradiographic distribution of [3H](+)-pentazocine and [3H]1,3-di-o-tolylguanidine (DTG) binding sites in guinea pig brain: a comparative study." Brain Research, vol. 581, no. 1, 1992, pp. 33-8.|
|Bowen WD, Walker JM, de Costa BR, Wu R, Tolentino PJ, Finn D, Rothman RB, Rice KC. "Characterization of the enantiomers of cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1- pyrrolidinyl)cyclohexylamine (BD737 and BD738): novel compounds with high affinity, selectivity and biological efficacy at sigma receptors." The Journal of pharmacology and experimental therapeutics, vol. 262, no. 1, 1992, pp. 32-40.|
|Sahin M, Bowen WD, Donoghue JP. "Location of nicotinic and muscarinic cholinergic and mu-opiate receptors in rat cerebral neocortex: evidence from thalamic and cortical lesions." Brain Research, vol. 579, no. 1, 1992, pp. 135-47.|
|Berson DM, Graybiel AM, Bowen WD, Thompson LA. "Evidence for intrinsic expression of enkephalin-like immunoreactivity and opioid binding sites in cat superior colliculus." Neuroscience, vol. 43, no. 2-3, 1991, pp. 513-29.|
|Wiest PM, Olds GR, Bowen WD. "Schistosoma mansoni: protein phosphorylation during transformation of cercariae to schistosomula." Experimental parasitology, vol. 73, no. 2, 1991, pp. 214-22.|
|Hellewell SB, Bowen WD. "A sigma-like binding site in rat pheochromocytoma (PC12) cells: decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that of guinea pig brain." Brain Research, vol. 527, no. 2, 1990, pp. 244-53.|
|Bowen WD, DeCosta B, Hellewell SB, Thurkauf A, Walker JM, Rice KC. "Characterization of [3H] (+)-pentazocine, a highly selective sigma ligand." Progress in clinical and biological research, vol. 328, 1990, pp. 117-20.|
|Matsumoto RR, Bowen WD, Walker JM. "Down-regulation of sigma receptors by chronic haloperidol." Progress in clinical and biological research, vol. 328, 1990, pp. 125-8.|
|Matsumoto RR, Hemstreet MK, Lai NL, Thurkauf A, De Costa BR, Rice KC, Hellewell SB, Bowen WD, Walker JM. "Drug specificity of pharmacological dystonia." Pharmacology Biochemistry and Behavior, vol. 36, no. 1, 1990, pp. 151-5.|
|Walker JM, Patrick SL, Thurkauf A, Rice KC, Bowen WD. "Inhibition of cholinergic analgesia by (+)-opiates." Progress in clinical and biological research, vol. 328, 1990, pp. 81-4.|
|Bowen WD, Tolentino P, Varghese P. "Investigation of the mechanism by which sigma ligands inhibit stimulation of phosphoinositide metabolism by muscarinic cholinergic agonists." Progress in clinical and biological research, vol. 328, 1990, pp. 21-4.|
|Bowen WD, Moses EL, Tolentino PJ, Walker JM. "Metabolites of haloperidol display preferential activity at sigma receptors compared to dopamine D-2 receptors." European journal of pharmacology, vol. 177, no. 3, 1990, pp. 111-8.|
|Walker JM, Bowen WD, Walker FO, Matsumoto RR, De Costa B, Rice KC. "Sigma receptors: biology and function." Pharmacological reviews, vol. 42, no. 4, 1990, pp. 355-402.|
|Bluth LS, Rice KC, Jacobson AE, Bowen WD. "Acylation of sigma receptors by Metaphit, an isothiocyanate derivative of phencyclidine." European journal of pharmacology, vol. 161, no. 2-3, 1989, pp. 273-7.|
|Matsumoto RR, Bowen WD, Walker JM. "Age-related differences in the sensitivity of rats to a selective sigma ligand." Brain Research, vol. 504, no. 1, 1989, pp. 145-8.|
|Bowen WD, Hellewell SB, McGarry KA. "Evidence for a multi-site model of the rat brain sigma receptor." European journal of pharmacology, vol. 163, no. 2-3, 1989, pp. 309-18.|
|Forster J, Morris AS, Shearer JD, Mastrofrancesco B, Inman KC, Lawler RG, Bowen W, Caldwell MD. "Glucose uptake and flux through phosphofructokinase in wounded rat skeletal muscle." The American journal of physiology, vol. 256, no. 6 Pt 1, 1989, pp. E788-97.|
|Goldstein SR, Matsumoto RR, Thompson TL, Patrick RL, Bowen WD, Walker JM. "Motor effects of two sigma ligands mediated by nigrostriatal dopamine neurons." Synapse (New York, N.Y.), vol. 4, no. 3, 1989, pp. 254-8.|
|Dudek SM, Bowen WD, Bear MF. "Postnatal changes in glutamate stimulated phosphoinositide turnover in rat neocortical synaptoneurosomes." Brain research. Developmental brain research, vol. 47, no. 1, 1989, pp. 123-8.|
|Bowen WD, Walker JM, Yashar AG, Matsumoto RR, Walker FO, Lorden JF. "Altered haloperidol-sensitive sigma receptors in the genetically dystonic (dt) rat." European journal of pharmacology, vol. 147, no. 1, 1988, pp. 153-4.|
|Bowen WD, Rodrigues PA, Wanzor TE, Jacobson AE, Rice KC. "Differential coupling of mu-competitive and mu-noncompetitive delta opiate receptors to guanine nucleotide binding proteins in rat brain membranes." Biochemical pharmacology, vol. 37, no. 3, 1988, pp. 467-72.|
|Walker JM, Bowen WD, Thompson LA, Frascella J, Lehmkuhle S, Hughes HC. "Distribution of opiate receptors within visual structures of the cat brain." Exp Brain Res, vol. 73, no. 3, 1988, pp. 523-32.|
|Walker JM, Matsumoto RR, Bowen WD, Gans DL, Jones KD, Walker FO. "Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs." Neurology, vol. 38, no. 6, 1988, pp. 961-5.|
|Kooper GN, Levinson NR, Copeland CF, Bowen WD. "Photoaffinity labeling of opiate receptors using intrinsically photoactive 3H-opiates." Molecular pharmacology, vol. 33, no. 3, 1988, pp. 316-26.|
|Bowen WD, Kirschner BN, Newman AH, Rice KC. "Sigma receptors negatively modulate agonist-stimulated phosphoinositide metabolism in rat brain." European journal of pharmacology, vol. 149, no. 3, 1988, pp. 399-400.|
|Walker JM, Coy DH, Young EA, Baldrighi G, Siegel SF, Bowen WD, Akil H. "[D-Ala2, (F5) Phe4]-dynorphin 1-13-NH2 (DAFPHEDYN): a potent analog of dynorphin 1-13." Peptides, vol. 8, no. 5, 1987, pp. 811-7.|
|Bowen WD, Hellewell SB, Kelemen M, Huey R, Stewart D. "Affinity labeling of delta-opiate receptors using [D-Ala2,Leu5,Cys6]enkephalin. Covalent attachment via thiol-disulfide exchange." Journal of Biological Chemistry, vol. 262, no. 28, 1987, pp. 13434-9.|
|Walker JM, Bowen WD, Atkins ST, Hemstreet MK, Coy DH. "Mu-opiate binding and morphine antagonism by octapeptide analogs of somatostatin." Peptides, vol. 8, no. 5, 1987, pp. 869-75.|
|Bowen WD, Kelemen M, Huey R, Stewart D. "Characterization of D-Ala2,Leu5,Cys6-enkephalin: a novel synthetic opioid peptide with slowed dissociation from delta receptors." NIDA research monograph, vol. 75, 1986, pp. 193-6.|
|Bowen WD, Kooper G. "Photoaffinity labeling of opiate receptors with 3H-etorphine: possible species differences in glycosylation." NIDA research monograph, vol. 75, 1986, pp. 17-20.|
Most work in our laboratory currently focuses on the possible role of sigma-2 receptors in regulation of cell proliferation and survival. We have found that chronic activation of sigma-2 receptors induces apoptosis in a wide variety of cell types. We are investigating the signaling mechanisms leading to the induction of cell death, and have found that these mechanisms are cell type-specific. For example, in breast tumor cells, apoptosis occurs via a novel mechanism that is both caspase- and p53-independent, whereas in neuroblastoma, cell death is dependent on caspase 8/10 activation. Signaling involves both transient and sustained changes in cytosolic calcium levels. We are interested in determining the mechanisms of calcium flux and the downstream effects of these calcium signals. Signaling also involves changes in cellular sphingolipids (ceramides and lysosphingolipids). Sphingolipids are involved in myriad cellular processes including cell survival, regulation of ion channels, and cell-cell recognition. Lysosphingolipids act via specific G-protein coupled receptors on the cell surface, as well as through certain intracellular targets, and ceramides are known to modulate the activity of various protein kinases and phosphatases involved in cell growth. We are investigating the role of sphingolipid signaling in neuronal and non-neuronal cells and how this system interfaces with sigma-2 receptors. Also under investigation are effects of sigma-2 receptor activation on mitochondria. Apoptosis in both neuronal and non-neuronal cell types appears to involve loss of mitochondrial membrane potential and release of mitochondrial apoptogenic factors. The roles of mitochondrial pro- and anti-apoptotic Bcl-2 family proteins are under study.
The study of a series of SN79 analogs has revealed a previously unknown function of the sigma-2 receptor. Some ligands in this series induce programmed cell death by mechanisms described above. However, other ligands induce no apparent change in cell viability, but rather appear to stimulate hallmarks of glycolytic cellular metabolism. This is initially evidenced by an increase in reduction of MTT dye, an effect blocked by sigma-2 antagonists. We have shown that ligands in this class induce an increase in ATP levels, a decrease in basal ROS level, and stabilization of HIF1α with subsequent induction of VEGF expression. These results suggest that sigma-2 receptors may play some role in regulating the Warburg effect (aerobic glycolysis) and enhancing the ability of cancer cells to survive in hypoxic environment. This effect would be consistent with the upregulation of sigma-2 receptors in cancer cells. We are investigating additional sigma-2 receptor-mediated changes in metabolic endpoints and attempting to elucidate upstream signaling mechanisms leading to this metabolic effect.
The sigma-2 receptor, a 21.5 kDa lipid raft protein, has recently been identified as the known protein, TMEM97. While little is known about the function of TMEM97, this discovery has made available molecular tools with which to study sigma-2R/TMEM97 and will greatly facilitate further studies of this receptor and its role in normal and cancer cell biology.
The sigma-1 receptor has been cloned and is a 25 kDa polypeptide with two putative transmembrane domains. In contrast to sigma-2 receptors, activation of sigma-1 receptors appears to exert protective and perhaps trophic effects on neurons and other cell types. Others have shown that activation of sigma-1 receptors potentiates neurite outgrowth in culture, whereas we have shown that activation of sigma-2 receptors causes neurite retraction. Blockade of sigma-1 receptors by selective antagonists or antisense deoxyoligonucleotides has been shown to block the toxic effects of cocaine, a psychotropic agent that binds to sigma-1 receptors. Furthermore, sigma-1 receptor activation in the hippocampus has a cognitive enhancing effect. We have initiated structure-function studies of the sigma-1 receptor and its role in tumor cell proliferation and survival. Sigma-1 receptors regulate calcium signaling by amplifying release of calcium from the endoplasmic reticulum in response to the rise in IP3 via GPCR activation. The sigma-1 receptor appears to signal solely by protein-protein interactions. The liganded receptor binds to ankyrin in the ER membrane and relieves a tonic inhibition of the IP3 receptor that is imparted by its interaction with ankyrin. We have shown that stable overexpression of sigma-1 receptors induces a constitutive activation of the IP3 receptor in human MCF-7 breast tumor cells, which are normally devoid of sigma-1 receptors. Furthermore, studies using various receptor constructs showed that only the C-terminal segment of the receptor is required for this effect. We are further delineating the functional domains of the receptor. Furthermore, cells overexpressing active sigma-1 constructs proliferate more rapidly than untransfected cells and have a survival advantage. We are investigating the signaling mechanisms that are involved in inducing what appears to be a more highly aggressive phenotype. The studies suggest that the sigma-1 receptor could be a biomarker for assessing proliferative status of tumor cells.
We are involved in the design and synthesis of novel small molecule ligands for sigma-1 and sigma-2 receptors. Since the natural ligand(s) is unknown and many existing sigma ligands interact with other receptors, selective synthetic probes for sigma receptors are necessary. Through close collaboration with medicinal chemists, we have developed and are continuing to develop highly selective receptor agonists and antagonists for use as tools to study receptor function. We are interested in elucidating the structural features of ligands that determine binding affinity, impart subtype selectivity, and that specify agonist/antagonist properties. Some of these compounds may have clinical potential as therapeutic agents.
Studies of sigma receptors will shed light on novel modes for regulation of cell proliferation and survival. It may be possible to target sigma-2 receptors with agonists or sigma-1 receptors with antagonists to induce apoptosis in tumors rendered drug-resistant due to acquisition of mutations in key components of the classical apoptotic pathway, such as p53 and caspases. Also, the potential role of sigma-2 receptors in cancer cell metabolism may lead to other targets to induce cell death. Sigma receptors in the CNS could conceivably play a role in neurodegenerative disorders. Furthermore, since typical neuroleptics such as haloperidol activate sigma-2 receptors, these studies may have important implications for treatment of psychiatric disorders with respect to the debilitating motor side effects induced by these agents.
Wei, Z., Qi, J., Dai, Y., Bowen, W.D., and Mousseau, D.D. (2009) Haloperidol disrupts Akt signalling to reveal a phosphorylation-dependent regulation of pro-apoptotic Bcl-XS function. Cellular Signalling 21: 161-168.
Liu, Q., Bhat, M., Bowen, W.D., Cheng, J. Signaling pathways from activation of CB1 receptor to inhibition of NMDA-mediated calcium influx and neurotoxicity in dorsal root ganglion neurons. J. Pharmacol. Exp. Ther. 331: 1062-1070, 2009.
Wu, Z. and Bowen, W.D. (2008) Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: Constitutive enhancement of calcium signaling in MCF-7 tumor cells. J. Biol. Chem. 283: 28198-28215.
Martin-Fardon, R., Maurice, T., Aujla, H., Bowen, W.D., and Weiss, F. (2007) Diffferential effects of sigma-1 receptor blockade on self-administration and conditioned reinstatement motivated by cocaine vs. natural reward. Neuropsychopharmacol. 32: 1967-1973.
Gebreselassie, D. and Bowen, W.D. (2004) Sigma-2 receptors are specifically localized to lipid rafts of rat liver membranes. Eur. J. Pharmacol. 493: 19-28.
Matsumoto, R.R., Potelleret, F.H., Mack, A., Pouw, B., Zhang, Y., and Bowen, W.D. (2004) Structure-activity comparison of YZ-069, a novel sigma ligand, and four analogs in receptor binding and behavioral studies. Pharmacol. Biochem. Behav. 77: 775-781.
Romieu, P., Martin-Fardon, R., Bowen, W.D., and Maurice, T. (2003) Sigma1 receptor-related neuroactive steroids modulate cocaine-induced reward. J. Neurosci. 23: 3572-3576.
Cao, J.J., Kulkarni, S.S., Husbands, S.M., Bowen, W.D., Williams, W., Kopajtic, T., Katz, J.L., George, C., and Newman, A.H. (2003) Dual probes for the dopamine transporter and the sigma-1 receptors: Novel piperazinyl alkyl-bis-(4'-fluorophenyl)amine analogs as potential cocaine-abuse therapeutics. J. Med. Chem. 46: 2589-2598.
Crawford, K.W., Bittman, R., Chun, J., Byun, H.S., and Bowen, W.D. (2003) Novel ceramide analogs display selective cytotoxicity in drug-resistant breast tumor cell lines compared to normal breast epithelial cells. Cell. Mol. Biol. 49: 1017-1023.
Crawford, K.W. and Bowen, W.D. (2002) Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines. Cancer Res. 62: 313-322.
Crawford, K.W., Coop, A., and Bowen, W.D. (2002) Sigma-2 receptors regulate changes in sphingolipid levels in breast tumor cells. Eur. J. Pharmacol. 443: 207-209.
Matsumoto, R.R., McCracken, K.A., Pouw, B., Zhang, Y., and Bowen, W.D. (2002) Involvement of sigma receptors in the behavioral effects of cocaine: evidence from novel ligands and antisense oligodeoxynucleotides. Neuropharmacol. 42: 1043-1055.
Vilner, B.J. and Bowen, W.D. (2000) Modulation of cellular calcium by sigma-2 receptors: Release from intracellular stores in human SK-N-SH neuroblastoma cells. J. Pharmacol. Exp. Ther. 292: 900-911.
John, C.S., Vilner, B.J., Geyer, B.C., Moody, T., and Bowen, W.D. (1999) Targeting sigma receptor-binding benzamides as in vivo diagnostic and therapeutic agents for human prostate tumors. Cancer Res. 59: 4578-4583.
|Bazemore-Walker, Carthene||Adjunct Associate Professor of Chemistry|
|Marshall, John||Professor of Medical Science|
|Zimmerman, Anita||Professor of Medical Science, Vice Chair of Molecular Pharmacology, Physiology and Biotechnology, Graduate Program Director for the Molecular Pharmacology & Physiology Graduate Program|
|BIOL 2170 - Molecular Pharmacology and Physiology|
|BIOL 3662 - IMS-3 Cardiovascular|
|BIOL 3663 - IMS-3 Pulmonary|
|BIOL 3664 - IMS-3 Renal|
|BIOL 3674 - IMS-3 Human Reproduction|