540 E Canfield Ave, Detroit, MI 48201
3355 Scott Hall
My research has focused primarily on the cellular and molecular regulation of gene expression within CNS dopamine (DA) neurons and their forebrain targets, including dysfunctional gene expression in brain disorders. In particular, we have used complementary approaches encompassing cell culture, animal models, and human postmortem brain to investigate the biological processes contributing to drug abuse and Parkinson's disease.
1. One of my initial lines of research led to the identification of important differences in the physiological characteristics, drug responsiveness, and susceptibility to disease among subgroups of midbrain DA neurons. Early work entailed rodent studies, but this was subsequently expanded to the analysis of human midbrain.
- Bannon, M.J., Michaud, R.L., and Roth, R.H. Mesocortical dopamine neurons: Lack of autoreceptors modulating dopamine synthesis. Mol. Pharmacol. 19: 270-175, 1981. PMID:6785571 (>200 citations)
- Bannon, M.J., Reinhard, J.F., Jr., Bunney, E.B., and Roth, R.H. Unique response to antipsychotic drugs is due to the absence of terminal autoreceptors in mesocortical dopamine neurons. Nature 296: 444-446, 1982. PMID:7063040 (>100 citations)
- Bannon, M.J. and Roth, R.H. Pharmacology of mesocortical dopamine neurons. Pharmacol. Rev. 35: 53-68, 1983. PMID:6138783 (>500 citations)
- Chiodo, L.A., Bannon, M.J., Grace, A.A., Roth, R.H., and Bunney, B.S. Evidence for the absence of impulse-regulating somatodendritic and synthesis-modulating nerve terminal autoreceptors on subpopulations of mesocortical dopamine neurons. Neurosci. 12: 1-16, 1984. PMID:6462443 (>250 citations)
- Bannon, M.J. and Whitty, C.J. Age-related and regional differences in dopamine transporter mRNA expression in human midbrain. Neurology, 48, 969-977, 1997. PMID:9109886 (>100 citations)
2. Given the physiological interactions between DA cells and certain tachykinin-producing neurons, we next conducted some seminal studies aimed at better understanding the cellular distribution, regulation of gene expression, RNA alternative splicing, and physiological effects of tachykinin neuropeptides and their related neurokinin receptors.
- Bannon, M.J., Elliott, P.J., Alpert, J.E., Goedert, M., Iversen, S.D., and Iversen, L.L. Role of endogenous substance P in stress induced activation of mesocortical dopamine neurons. Nature 306: 791-792, 1983. PMID:6197656 (>100 citations)
- Bannon, M.J., Lee, J.-M., Giraud, P., Young, A., Affolter, H.-U, and Bonner, T.I. The dopamine antagonist haloperidol decreases substance P, substance K, and preprotachykinin mRNAs in rat striatonigral neurons. J. Biol. Chem. 261: 6640-6642, 1986. PMID:2422168 (>100 citations)
- Haverstick, D.M. and Bannon, M.J. Evidence for dual mechanisms involved in methamphetamine-induced increases in striatal preprotachykinin mRNA. J. Biol. Chem. 264: 13140-13144, 1989. PMID:2753904
- Helke, C.J., Krause, J.E., Mantyh, P.W., Couture, R. and Bannon, M.J. Diversity in mammalian tachykinin peptidergic neurons: Multiple peptides, receptors and regulatory mechanisms. FASEB J. 4: 1606-1615, 1990. PMID:1969374 (>400 citations)
- Whitty, C.J., Paul, M.A. and Bannon, M.J. Neurokinin receptor mRNA localization in human midbrain dopamine neurons. J. Comp. Neurol. 382, 394-400, 1997. PMID:9183701
3. The DA transporter plays a critical role in regulating extracellular DA levels. It is also a primary site of action for cocaine and other stimulants, as well as for the accumulation of neurotoxins that induce parkinsonism. A primary focus of the lab for a number of years was to increase our understanding regarding the regulation of DA transporter gene expression, including the basis for its exquisite DA cell-specificity of expression.
- Bannon, M.J., Poosch, M.S., Xia, Y., Goebel. D., Cassin, B. and Kapatos, G. Dopamine transporter mRNA content in human substantia nigra decreases with age. Proc. Natl. Acad. Sci. USA. 89, 7095-7099, 1992. PMID:1353885 (>100 citations)
- Sacchetti, P., Brownschidle, L.A., Granneman, J.G. and Bannon, M.J. Characterization of the 5’- flanking region of the human dopamine transporter gene. Mol. Brain Res., 74, 164-174, 1999. PMID:10640687 (>100 citations)
- Sacchetti, P., Mitchell, T.R., Granneman, J.G. and Bannon, M.J. Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism. J. Neurochem, 76, 1565-1572, 2001. PMID:11238740 (>100 citations)
- Michelhaugh, S.K., Fiskerstrand, C., Lovejoy, E. and Bannon, M.J. and Quinn, J.P. The dopamine transporter gene (SLC6A3) variable number of tandem repeats domain enhances transcription in dopamine neurons. J. Neurochem. 79, 1033-1038, 2001. PMID:11739616 (>100 citations)
4. Recently, as part of an international consortium, we have used this information to develop a novel strategy to rescue and enhance the functionality of surviving DA cells in animal models of Parkinson’s disease. The approach entails the regulated expression of trophic factors selectively within DA neurons, which we achieve by coupling receptor-mediated polyplex transfection of DA neurons with DA cell-specific transgene expression under the control of either the DA transporter gene promoter or a nurr1 response element we determined was critical for maintenance of DA phenotype.
- Gonzalez-Barrios, J.A., Lindahl, M., Bannon, M., Anaya-Martinez, V., Flores, G., Navarro-Quiroga, I., Trudeau, L.-E., Aceves, J., Martinez-Arguelles, D.B., Garcia-Villegas, R., Jiménez, I., Segovia, J. and Martinez- Fong, D. Neurotensin-polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats. Mol. Therapy 14, 857-865, 2006. PMID:17015039
- Martinez-Fong, D, Bannon, M.J., Trudeau, L.-E., Gonzalez-Barrios, J.A., Arango-Rodriguez, M.L., Hernandez- Chan, N.G., Reyes-Corona, D, Armendáriz-Borunda, J. and Navarro-Quiroga, I. NTS-polyplex: A potential nanocarrier for neurotrophic therapy of Parkinson’s disease. Nanomedicine: Nanotechnology, Biology and Medicine 8(7):1052-69, 2012. PMID:22406187
- Hernandez-Chan, N.G., Bannon, M.J., Orozco-Barrios, C.E., Escobedo, L., Zamudio, S., De la Cruz, F., Gongora-Alfaro, J.L., Armendáriz-Borunda, J., Reyes-Corona, D., Espadas-Alvarez, A.J., Flores- Martinez, Y.M., Ayala-Davila, J., Hernandez-Gutierrez, M.E., Pavón, L., García-Villegas, R., Nadella, R., Martinez-Fong, D. Neurotensin-polyplex-mediated brain-derived neurotrophic factor gene delivery into nigral dopamine neurons prevents nigrostriatal degeneration in a rat model of early Parkinson's disease. Journal of Biomedical Science 22(1):59, 2015. PMID:26198255
- Espadas-Alvarez, A.J., Bannon, M.J., Orozco-Barrios, C.E., Escobedo-Sanchez, L., Ayala-Davila, J., Mejia- Castillo, T., and Martinez-Fong, D. Regulation of human GDNF gene expression in nigral dopaminergic neurons using a new doxycycline-regulated NTS-polyplex nanoparticle system. Nanomedicine: Nanotechnology, Biology and Medicine (in press) 2017.
5. Persistent cellular and behavioral adaptations seen in drug addiction are encoded by long-lasting alterations in CNS gene expression. For a number of years now, we have followed the less common path of investigating such changes in human postmortem brain from cocaine or opioid abusers. Some studies have focused in detail on specific candidate genes, while other investigations have been more unbiased and discovery-driven in nature. Illustrative of the power of discovery-driven studies, we identified robust (but completely unanticipated) changes in the expression of myelin-related genes that were specific to cocaine abusers and for which clinical correlates have been identified. Ongoing collaborative projects continue to identify key molecular changes in brain regions and networks involved in human drug abuse.
- Albertson, D.N., Pruetz, B., Schmidt, C.J., Kuhn, D.M., Kapatos, G. and Bannon, M.J. Gene expression profile on the nucleus accumbens of human cocaine abusers: Evidence for dysregulation of myelin. J. Neurochem. 88:1211-1219, 2004. PMID:15009677. (>100 citations)
- Albertson, D.N., Schmidt, C.J., Kapatos, G. and Bannon, M.J. Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology 31:2304-2312, 2006. PMID:16730917
- Michelhaugh, S.K., Lipovich, L., Blythe, J., Jia, H., Kapatos, G. and Bannon, M.J. Mining Affymetrix Microarray data for long noncoding RNAs: altered expression in the nucleus accumbens of heroin abusers. J. Neurochem.116:459-66, 2011. PMID:21128942
- Ökvist, A., Fagergren, P., Whittard, J., Garcia-Osta, A., Drakenberg, K., Horvath, M., Schmidt, C.J., Keller, E., Bannon, M.J. and Hurd, Y.L. Dysregulated post-synaptic density and endocytic zone in the amygdala of human heroin and cocaine abusers. Biol. Psychiatry 69:245-52, 2011. PMID:21126734
- Anderson, S.A.R., Michaelides, M., Zarnegar, P., Ren, Y., Fagergren, P., Thanos, P.K., Wang, G.J., Bannon, M., Neumaier, J., Keller, E., Volkow, N.D. and Hurd, Y.L. Impaired periamygdaloid-cortex prodynorphin is characteristic of opiate addiction and depression. J. Clinical Investigation 123(12):5334-41, 2013. PMID:24231353
- Zhou, Y., Michelhaugh, S.K., Schmidt, C.J., Liu, J.S., Bannon, M.J. and Lin, Z. Ventral midbrain correlation between genetic variation and expression of the dopamine transporter in cocaine-abusing subjects versus non-abusing subjects. Addiction Biology 19(1):122-31, 2014.PMID:22026501.
- Bannon, M.J., Johnson, M.M., Michelhaugh, S.K., Hartley, Z.J., Halter, S.D., David, J.A., Kapatos, G., and Schmidt, C.J. A molecular profile of cocaine abuse includes the differential expression of genes that regulate transcription, chromatin and dopamine cell phenotype.Neuropsychopharmacology 39(9):2191-9, 2014. PMID:24642598
- Bannon, M.J., Savonen, C.L., Jai, H., Dachet, F., Halter, S.D., Schmidt, C.J., Lipovich, L. and Kapatos, G. Identification of long noncoding RNAs dysregulated in the midbrain of human cocaine abusers. J Neurochem. 135(1):50-9, 2015. PMID:26222413
1976 B.A. Lewis University, Romeoville, IL. Psychology/Philosophy (Summa Cum Laude)
1978 M.S. University of Louisville, Louisville, KY. Pharmacology (Advisor: C.H. Jarboe)
1979 M.Phil Yale University, New Haven, CT.
1982 Ph.D. Yale University, New Haven, CT. Pharmacology (Advisor: R.H. Roth)
1982 Postdoctoral Associate Department of Pharmacology Yale University School of Medicine (Mentor: R.H. Roth)
1982-1983 Postdoctoral Fellow MRC Neurochemical Pharmacology Unit Medical Research Council Center, Cambridge (Mentors: L.L. Iversen/S.D. Iversen)
1983-1984 Guest Researcher Laboratory of Cell Biology National Institute of Mental Health (Mentor: M.J. Brownstein)