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Photo of Thomas J. Abbruscato Name: Thomas J. Abbruscato
Position: Associate Dean for GSBS, Graduate Program Advisor & Associate Professor
Email: Thomas.Abbruscato@ttuhsc.edu
Bio Dr. Abbruscato joined the Pharmaceutical Sciences faculty in January of 2000. He received both a B.S. (Molecular and Cellular Biology) and Ph.D. (Pharmacology and Toxicology) from the University of Arizona. He continued his education as a NRSA research fellow in the University of Arizona, College of Medicine studying the effects of stroke on the cerebrovasculature. Currently he serves on the Editorial Advisory Board for the Journal of Pharmacology and Experimental Therapeutics and Life Sciences. He also maintains a regular membership on the Brain Injury Neurovascular Pathologies (BINP) NIH Study Section. His research is funded by the National Institute of Neurological Disorders and Stroke investigating the combined effects of tobacco smoke chemicals and brain ischemia on neuronal recovery to potentially identify therapeutic targets for novel stroke treatments targeting edema and brain ion homeostasis.

Education:

B.S. Molecular and Cellular Biology, University of Arizona, 1992

Ph.D. Pharmacology and Toxicology, University of Arizona, 1997

NRSA Research Fellow University of Arizona, College of Medicine studying the effects of stroke on the cerebrovasculature, 1997-1999

Research Interests:

Understanding blood-brain barrier (BBB) pathophysiology after stroke is critical since stroke is a leading cause of death and disability in the world. Our research investigates the effects of stroke (hypoxia/aglycemia) on nutrient and ion transport across the BBB and expression of tight juctional and cytoskeletal proteins in barrier cell types. This research also investigates both the acute and chronic effects of tobacco smoke constituents of BBB integrity and response to hypoxia/aglycemia resulting from ischemia. We hope to identify key biochemical and molecular mechanisms involved in tobacco smoke constituent alteration in BBB function during stroke so that individualized stroke therapies can be designed to improve health outcomes for both smoking and non-smoking patients.

Publications:

Weber, S.J., Abbruscato, T.J., Lipkowski, A.W., Polt, R., Misicka, A., Haaseth, R.C., Bartosz, H., Hruby, V.J., Davis, T.P. Assessment of an in vitro blood-brain barrier using several [Met5] Enkephalin opioid analogs. J. Pharmacol. Exp. Ther. 266: 1649-1655, 1993.

Brownson, E.A., Abbruscato, T.J., Gillespie, T.J., Hruby, V.J. and Davis, T.P. Effect of peptidases at the blood-brain barrier on the permeability of enkephalin. J. Pharmacol. Exp. Ther. 270: 675-680, 1994.

Polt, R., Porreca, F., Szabo, L.Z., Bilsky, E.J., Davis, P., Abbruscato, T.J., Davis, T.P., Horvath, R., Yamamura, H.I. And Hruby, V.J. Glycopeptide enkephalin analogues produce analgesia in mice: Evidence for penetration of the blood-brain barrier. Proc. Natl. Acad. Sci. USA. 91: 7114-7118, 1994.

Davis, T.P., Abbruscato, T.J., Brownson, E.A. and Hruby, V.J. Conformationally constrained peptide drugs targeted at the blood-brain barrier. NIDA Research Monograph 154: 47-59, 1994.

Abbruscato, T.J., Williams, S.A., Hruby, V.J. and Davis, T.P. Blood-brain permeability of novel opioid peptides using brain microvessel endothelial cells. NIDA Research Monograph, CPDD. 176: P256, 1995.

Williams, S.A. Abbruscato, T.J., Szabo, L., Polt, R., Hruby, V.J. and Davis, T.P. The effect of glycosylation on the uptake of an enkephalin analogue into the central nervous system. Adv. Exp. Med. Biol. 69-77, 1995.

Williams, S.A. Abbruscato, T.J., Hruby, V.J. and Davis, T.P. Effect of halogenation on the CNS entry of DPDPE. NIDA Research Monograph, CPDD 176: P257, 1995.

Abbruscato, T.J., Williams, S.A., Misicka, A., Lipkowski, A.W., Hruby, V.J. and Davis, T.P. Blood-to-central nervous system entry and stability of biphalin, a unique double-enkephalin analog, and its halogenated derivatives. J. Pharmacol. Exp. Ther. 276: 1049-1057, 1996.

Williams, S.A. Abbruscato, T.J., Hruby, V.J. and Davis, T.P. The passage of a ?-opioid selective enkephalin, DPDPE, across the blood-brain and blood-cerebrospinal fluid barriers. J. Neurochem. 66: 1289-1299, 1996.

Greene, D.G., Hau, V., Abbruscato, T.J., Hom, S.J., Gillespie, T.J., Bartosz, H., Hruby, V.J. and Davis, T.P. Enkephalin analog prodrugs: assessment of in vitro conversion, enzyme cleavage characterization and blood-brain barrier permeability. J. Pharmacol. Exp. Ther. 277: 1366-1375, 1996.

Williams, S.A., Abbruscato, T.J., Szabo, L. Polt, R., Hruby, V.J., and Davis, T.P. The effect of glycosylation on the uptake of an enkephalin analogue into the CNS. In: Biology and Physiology of the BBB. Couraud and Scherman, Eds. Plenum Press, New York, 69-77, 1996.

Abbruscato, T.J., Williams, S.A., Hruby, V.J. and Davis, T.P. Blood-brain barrier permeability and bioavailability of a highly potent and mu-selective opioid receptor antagonist, CTAP: Comparison with morphine. J. Pharmacol. Exp. Ther. 280: 402-409, 1997.

Thomas, S.A., Abbruscato, T.J., Hruby, V.J. and Davis, T.P. The entry of DPDPE into the central nervous system: saturation kinetics and specificity. J. Pharmacol. Exp. Ther. 280: 1235-1240, 1997.

Abbruscato, T.J., Williams, S.A. , Hruby, V.J. and Davis, T.P. Brain and spinal cord distribution of Biphalin, correlation with opioid receptor density and mechanism of CNS entry. J. Neurochem. 69: 1236-1245, 1997.

Thomas, S.A., Abbruscato, T.J., Hruby, V.J. and Davis, T.P. In vitro blood-brain barrier permeability and stability of a series of [D-Ala2]deltorphin I and II analogues. J. Pharmacol. Exp. Ther. 281: 817-825, 1997.

Egleton D.R., Abbruscato, T.J., Thomas, S.A. and Davis, T.P. Transport of opioid peptides into the central nervous system. J. Pharm. Sci. 18: 1433-1439, 1998.

Abbruscato, T.J. and Davis, T.P. Rapid hypoxia / aglycemia compromises in vitro blood-brain barrier integrity. J. Pharmacol. Exp. Ther. 289: 668-675, 1999.

Gentry, C.L., Egleton, R.D., Gillespie, T.J., Abbruscato, T.J. Bechowski, H.B., Hruby, V.J. and Davis, T.P. The effect of halogenation on blood-brain barrier permeability of a novel peptide drug. Peptides 20: 1229-1238, 1999.

Abbruscato, T.J. and Davis, T.P. Hypoxia / aglycemia causes rapid decrease in protein expression of E-cadherin. Brain Research 842: 277-286, 1999.

Newcomb, R., Abbruscato, T.J., Singh, T., Nadashdi, L., Davis, T.P. and Miljanich, G.Bioavailability of omega-conopeptides in brain: Influx from blood, stability, and diffusion, Peptides 21: 491-501, 2000.

Crow, A.P., Lockman, P.R., Abbruscato, T.J., and Allen D.D. Novel choline transport characteristics in Caco-2 cells. Drug Dev Ind Pharm. 28 (7):773-781, 2002.

Abbruscato, T.J., Lopez, S.P., Mark, K.S., Hawkins, B.T. and Davis, T.P. Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci. 91 (12):2525-2538, 2002.

Lockman, P.R., Koziara, J., Roder, K.R., Paulson, J., Abbruscato, T.J., Mumper, R.J., and Allen, D.D. In vivo and in vitro assessment of baseline BBB parameters in the presence of novel nanoparticles. Pharm. Res. Vol. 20, No. 5, 705-713, 2003.

Abbruscato, T.J. Lopez, S.P. Roder, K.R., and Paulson, J.R. Regulation of BBB Na,K,2Cl-Cotransporter through phosphorylation during in vitro stroke conditions. J. Pharmacol. Exp. Ther. 310 (2) 459-468, 2004.

Yang, T., Hussain, A., Paulson, J.R., Abbruscato, T.J., Ahsan, F. Effect of cyclodextrins on nasal delivery of low molecular weight heparins: in vivo and in vitro studies. Pharm. Res. 7: 1127-1136, 2004.

Hawkins, B.J., Abbruscato, T.J., Egleton, R.D., Brown, R.C., Huber, J.D., Campos, C.R., and Davis, T.P. Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junctional protein distribution. Brain Research 1027: 48-58, 2004.

Rudd, K., Raehl, C.L., Abbruscato, T.J., Bond, C.A., Stenhouse, A.C. Current Approaches to Assessing Medication-Related Anticholinergic Potential. Pharmacotherapy 11: 1592-1601, 2005.

Lockman, P.R., McAfee, G., Geldenhuys, W.J., Van der Schyf, C.J., Abbruscato, T.J., and Allen, D.D. Brain uptake kinetics of nicotine and cotinine after chronic nicotine exposure. J. Pharmacol. Exp. Ther. (In Press) 2005.

Mdzinarishvili, A., Geldenhuys, W.J., Abbruscato, T.J., Bickel, U., Klein, J., Van der Schyf, C.J. NGP1-01, a lipophilic polycyclic cage amine, is neuroprotective in focal ischemia. Neuros. Lett. 314(2):636-642, 2005.

Lockman, P.R., Van der Schyf, C.J., Abbruscato, T.J., and Allen, D.D. Chronic nicotine exposure alters blood brain barrier permeability and diminishes brain uptake of methyllycaconitine. J. Neurochem. 94(1): 37-44, 2005.

Paulson, J.R., Roder, K.E., McAfee, G., Allen, D.D., Van der Schyf, C.J., Abbruscato, T.J. Tobacco smoke chemicals attenuate brain-to-blood potassium transport mediated by Na,K,2Cl-cotransporter during hypoxia-reoxygenation. J. Pharmacol. Exp. Ther. 316(1): 248-254, 2006.

Yang, T. Roder, K.E., Bhat, G.J., Thekkumkara, T.J. and Abbruscato, T.J. Protein kinase C family members in the regulation of blood-brain barrier Na,K,2Cl-cotransporter during in vitro stroke conditions and nicotine exposure. Pharm. Res. 23(2): 291-302, 2006.

Lockman, P.R., Gaasch, J., McAfee, G. Abbruscato, T.J., Van der Schyf, C.J., and Allen, D.D. Nicotine exposure does not alter plasma to brain choline transfer. Neurochem. Res. (In Press) 2006.

Yang, T. and Abbruscato, T.J. Characterization of a mouse brain endothelial cell model of the blood-brain barrier. Pharm. Res. (In Prep) 2006.

Bai, S., Yang, T., Abbruscato, T.J., and Ahsan, F. Characterization of RPMI 2650 cell line as a model for nasal drug delivery. Pharm. Res. (In Prep) 2006.

Paulson, J.R., Mdzinarishvili, A., Roder, K.E., Van der Schyf, C.J., Klein, J., Bickel, U., and Abbruscato, T.J. Nicotine worsens edema associated with focal ischemia and water gain associated with oxygen-glucose deprived hippocampal brain slices. J. Pharmacol. Exp. Ther. (In Prep) 2006.

Vemula, S., Bhat, G.J., Thekkumkara, T.J. and Abbruscato, T.J. Sodium dependent glucose transport across the neurovascularture during oxygen glucose deprivation. (In Prep) 2006.