Michael J. Bannon, Ph.D. ProfessorWayne State University School of Medicine
540 E Canfield Ave, 3355 Scott Hall
Detroit, MI 48201
Telephone (313) 993-4271
Fax (313) 577-6739
Our lab is interested in the cellular and molecular regulation of gene expression within CNS dopamine (DA) neurons and their target neurons. Using complementary approaches involving cell culture, animal models and human postmortem brain, we study the biological processes contributing to drug abuse and Parkinson's disease.
Dopamine transporter gene: Regulation and role in CNS disorders. The neurotransmitter DA exerts important effects on locomotor activity, motivation and reward, and cognition. The DA transporter (DAT) is a DA neuron-specific plasma membrane protein that clears extracellular DA, thereby regulating the amplitude and duration of DA signaling. The DAT is also an important target for cocaine and other psychostimulants, DA-selective neurotoxins, and some drugs used in the treatment of attention deficit disorder and depression. Our lab has focused on understanding the regulation of DAT gene expression and alterations in DAT function associated with a variety of neuropsychiatric disorders. We've identified changes in DAT gene expression associated with the normal human aging process and with Parkinson's disease. In other experiments, we've identified DAT gene sequences contributing to cell-specificity of expression, using these sequences to drive DA cell-specific transgene expression in vivo to achieve biochemical and functional recovery in an experimental model of Parkinson's disease.
As mentioned above, the DAT is a critical target for cocaine, and we've identified changes in DAT gene expression in the cocaine-addicted human brain. Using a technical toolbox that includes transfection of DA cell lines and cultured DA neurons, manipulation and analysis of DAT expression in vivo (siRNA, ChIP) and human postmortem analyses, we've characterized cis- and trans-acting factors that influence DAT gene expression and the changes in DAT expression and DA phenotype seen with drug abuse. Recently, we've begun focusing on polymorphisms in the human DAT gene, allele-specific DAT expression, and gene x environment interactions seen with drug abuse.
Profiling gene expression and lncRNAs in the addicted human brain. Drug abuse is thought to induce long-lasting cellular and behavioral adaptations as a result of widespread alterations in gene expression. As a complement to our detailed studies of well-known candidate genes (e.g. DAT), we've been engaging in discovery-driven research, examining profiles of gene expression in postmortem brain from human cocaine and heroin abusers. Our initial studies, focused on the nucleus accumbens (the brain 'reward center'), demonstrated surprisingly distinct transcriptomes associated with chronic cocaine abuse as opposed to heroin abuse. Illustrative of the power of discovery-driven studies, we identified some robust but completely unanticipated cocaine-induced changes in the expression of genes controlling myelin development and maintenance, for which clinical correlates have been identified. Ongoing studies are extending gene profiling to other brain regions critical to human drug addiction, craving and relapse.
In other studies, we and our collaborators have developed computational and annotation pipelines for validating the expression of long non-coding RNA (lncRNA) transcripts, recently described top-down regulators of gene expression likely to be involved in drug abuse and other forms of neuroplasticity. Using commercial microarrays (and now lncRNA custom arrays), we've identified numerous lncRNAs whose abundance is altered in the brains of drug abusers. The overarching goal of our research is to identify novel targets and therapeutic strategies for brain disorders involving dysfunction of DA neurotransmission, such as drug abuse and Parkinson's disease.
CURRENT LAB PERSONNEL
- James David (research assistant)
SOME LAB ALUMNI
- Jun Wang (Postdoc 2001-05), now Assistant Professor (Neurology) University of Chicago
- Dawn Albertson (PhD 2005), now Associate (Psychology), Minnesota State University, Mankato
- Irina Calin-Jageman (Postdoc 2002-4), now Assistant Professor (Biology ) Dominican University
- Paola Sacchetti (PhD 2000), now Assistant Professor (Biology), Mount Holyoke College
- Maureen Hahn (PhD 1999) now Assistant Professor (Medicine & Pharmacology) Vanderbilt University
- Dennis Goebel (Postdoc 1992-4), now Associate Professor (Anatomy & Cell Biology) Wayne State University
- Yue Xia (Postdoc 1992-3), now Bioinformatics Program Officer, NIAID, NIH
- Amy Manning-Bog (Postdoc 1999-2000), now Program Manager, Neurodegenerative Disease Program, Stanford Research Institute
- Kazuhiko Shibata (Postdoc 1990-1), now Professor (Pharmaceutical Information Sciences), Matsuyama University, Japan
- Doris Haverstick (Postdoc 1998-9), now Associate Professor (Pathology), Director of Toxicology and Associate Director of Clinical Chemistry, University of Virginia
SELECTED RECENT PUBLICATIONS
- Albertson, D.N., Schmidt, C.J., Kapatos, G., and Bannon, M.J. Distinctive profile of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacol. 31, 2304-2312, 2006. PMID 16710320
- 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., Jimenez, 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.
- Gyawali, S., Subaran, R., Weissman, M.M., Hershkowitz, D., McKenna, M.C., Talati, A., Fyer, A.J., Wickramaratne, P., Adams, P.B., Hodge, S.E., Schmidt, C.J., Bannon, M.J. and Glatt, C.E. Association of a Polyadenylation Polymorphism in the Serotonin Transporter and Panic Disorder. Biol. Psychiatry 67:331-8, 2010. PMID 19969287
- Okvist, 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
- 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
SOME LINKS OF INTEREST
Allen Brain Altas http://www.brain-map.org/
PHD Comics http://www.phdcomics.com/comics.php