Ph.D., Cornell University
Professor
Department of Molecular Pharmacology, Physiology, and Biotechnology
389 BioMedical Center
Tel: (401) 863-3253
Email: Wayne_Bowen@brown.edu
Go to lab web page

My research focuses on the structure and function of sigma receptors.  Sigma receptors recognize several important classes of psychotropic drugs, including antipsychotic agents such as haloperidol and some psychostimulants like cocaine. No endogenous ligands for these receptors have yet been clearly identified, although progesterone and other neurosteroids have been shown to interact with sigma-1 receptors.  We have demonstrated that activation of sigma-2 receptors results in apoptotic cell death in neuronal and non-neuronal cell lines and in cultures of primary neurons.  We are therefore investigating the role of sigma-2 receptors in cell proliferation and survival, with implications for the neurotoxic effects of psychotropic agents and neurodegenerative diseases.  We are studying the primary signal transduction pathways utilized by sigma-2 receptors, with particular interest in effects on calcium mobilization and production of sphingolipid second messengers.  We are delineating the role of various cellular proteins and organelles known to be mediators of apoptosis, including caspases, bcl-family proteins, mitochondria, and mitochondrial pro-apoptotic factors.  We are attempting to characterize the receptor protein and clone the gene expressing the sigma-2 receptor.  We are also interested in the design and synthesis of novel small molecule ligands and have active collaborations with medicinal chemists to develop sigma receptor-selective agonists and antagonists. My laboratory applies a multidisciplinary approach including tools of molecular pharmacology, cell biology, molecular biology, and proteomics.  We also utilize tools from the rapidly emerging field of lipidomics in our studies of bioactive sphingolipids and their signaling pathways.

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.

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.

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.

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.

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.

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.

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.

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.