Dr. Cowan’s research laboratory explores the genes and molecular mechanisms that control proper brain wiring during development, and they seek to understand the roles of these molecules in the young and adult brain under pathological conditions, such as autism, intellectual disability, drug addiction, and depression. The lab utilizes a broad array of experimental approaches to gain a better understanding about the underlying regulation, or dysregulation, of healthy brain function, and they take an integrated, multidisciplinary approach to address these important topics for human mental health.
The Cowan Lab explores the genes and molecular mechanisms that control proper brain wiring during development, and they seek to understand the roles of these molecules in the young and adult brain under pathological conditions, such as autism, intellectual disability, drug addiction, and depression. The lab utilizes a broad array of experimental approaches to gain a better understanding about the underlying regulation, or dysregulation, of typical brain function, and they take an integrated, multidisciplinary approach to address these important topics for human mental health.
The lab employs a range of molecular, genetic and behavioral techniques to understand how abused substances hijack brain function to promote addiction-related behaviors. Through identification of new molecules involved in addiction, we ultimately seek to develop these molecules as potential therapeutics for treating drug addiction. The lab studies multiple molecules that are recruited by illicit drug use and participate in maladaptive brain changes that associate with addiction-related behaviors. Ongoing studies seek to identify the cellular mechanisms by which these identified molecules influence persistent drug taking and relapse.
The Cowan Lab has uncovered key brain development roles for several genes linked to risk for neurodevelopmental disorders, including autism, intellectual disability and schizophrenia. These molecules appear to work together during typical brain development to control the proper establishment of excitatory and inhibitory connections in the brain. Genetic abnormalities in these genes in humans often produce intellectual disability and autism-associated symptoms, and the lab observes similar symptoms in mice engineered to have disruptions in these same genes. By understanding the genetic and molecular underpinnings of autism spectrum disorders, the lab hopes to identify new therapeutic targets for treatment of autism, intellectual disability and related neurodevelopmental disorders in humans.
Christopher Cowan, Ph.D.
Professor, Departments of Neuroscience and Psychiatry
William E. Murray SmartState Endowed Chair of Excellence in Neuroscience
Chair, Department of Neuroscience
173 Ashley Avenue, BSB 410B
Charleston, SC 29425
Biography: Dr. Cowan is Professor and Chair of the Department of Neuroscience and the William E. Murray SmartState Endowed Chair in Neuroscience at the Medical University of South Carolina. Before moving his lab to MUSC in 2016, Dr. Cowan was an Associate Professor, Department of Psychiatry at Harvard Medical School and McLean Hospital where he served as the Director of the Integrative Neurobiology Laboratory from 2012-2016, and he was an Assistant Professor, Department of Psychiatry at the University of Texas Southwestern Medical School from 2005-2012. Dr. Cowan earned his bachelor of arts degree from Wesleyan University (CT) and his Ph.D. from Baylor College of Medicine (TX). He completed his postdoctoral training at Harvard Medical School and Boston Children’s Hospital in the area of molecular neurobiology.
Degree(s): B.S./B.A. in Psychology from the University of Nebraska-Lincoln in 2005, Ph.D. in Neuroscience from the University of Minnesota-Twin Cities in 2012.
Biography: Rachel is interested in studying mechanisms of experience-dependent plasticity in neurons. Her doctoral work focused on the development and characterization of a culture system designed to support the development of in vivo-like medium spiny neurons. This system can be used to investigate the molecular mechanisms of MSN development and plasticity. At MUSC, Rachel is working to study epigenetic mechanisms in drug addiction using a combination of molecular, cell biological, and behavioral approaches.
Degree(s): Bachelor in Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan; M.S. and Ph.D. in Biology- Tokyo Metropolitan University, Tokyo, Japan.
Biography: Makoto received his Ph.D. in biology under the supervision of Dr. Shin-ichi Hisanaga Tokyo, Japan. For his postdoctoral training, he joined the Cowan lab and studied molecular and behavioral neuroscience. As a current assistant professor at MUSC, he is interested in studying the mechanisms of epigenetic gene regulation underlying emotional experiences such as Drug reward/addiction and stress.
Degree(s): B.S. in Psychology, University of Florida, 2008; Ph.D. in Neuroscience, University of Florida, 2012
Biography: Ethan studies the maladaptive plastic effects of drugs of abuse. As a graduate student he studied morphine dependence and associated changes in NMDA receptors (GluNs), and as a postdoc he examined the role of BDNF-TrkB-PLC signaling in cocaine self-administration behaviors. He is currently studying the cell-specific effects of HDAC5 in cocaine and heroin addiction here in the Cowan Lab
Degree(s): B.S. in Biology, University of Louisiana Monroe; Ph.D. in Molecular and Cellular Biology, University of Alabama
Biography: Adam is interested in studying the molecular mechanisms underlying autism-spectrum disorders using the mouse model system. The Louisiana native earned his doctorate in the Caldwell lab at the University of Alabama, where he utilized the C. elegans model system to identify genetic modifiers of dopaminergic neuron degeneration and focused on the role of the lysosomal protein VPS41 as a potential therapeutic target for Parkinson's disease. As a postdoc with Dr. Christopher Cowan, Adam is using primary neuron cultures and mouse models to study the developmental requirement of the autism-associated transcription factor MEF2C in brain development, synapse regulation and autism-associated behaviors, and understand the molecular mechanisms underlying MEF2C-dependent synapse remodeling in cortical neurons.
Degree(s): Ph.D. in Neuroscience, Universite Pierre et Marie Curie Paris France, 2014; Master Degree in Biology, Universite de Rennes 1 France, 2010
Biography: Ahlem is interested in studying neural circuit development. Her doctoral work in the Gaspar Lab concerned the cellular mechanisms involved in mouse retinal projection development focusing on the role of synaptic release and cAMP signaling. Her post-doctoral work in the lab of Dr. Cowan investigates the role of EphB1 in axon guidance/brain wiring during development (thalamo-cortical system) and its role in adult behavior requiring synaptic plasticity (hippocampus, habenula).
Degree(s): B.S. in Neuroscience, Furman University; Ph.D. in Biomedical Science, Medical University of South Carolina
Biography: Sarah is interested in understanding drug-mediated neuroadaptations in addiction circuitry with a focus on prefrontal cortical subdivisions and associated afferents and efferents. For her doctoral dissertation work she studied the role of molecular and synaptic mechanisms behind the efficacy of a BDNF infusion to attenuate cocaine seeking behavior. Her work primarily focused on local phospho-protein signaling in addition circuit level manipulations using chemogenetic approaches. As a post-doc with Dr. Cowan, she is investigating the role that HDAC5 plays in the prefrontal cortex in a regional and cell-specific manner in preclinical drug abuse models.
Degree(s): B.S. in Biology, University of South Carolina-Beaufort, 2012; M.S. in Biotechnology, Claflin University, 2016
Biography: Brandon is interested in understanding the regulatory mechanisms of synaptic plasticity during memory consolidation and drug exposure. During his master’s thesis, he investigated the molecular effects of Zika virus and environmental mutagens on neuroblastoma cell models. As a PhD student in the Cowan lab, Brandon is using cutting-edge molecular tools and transgenic mice to understand the fundamental mechanisms of neuronal plasticity underlying learning and memory of drug reward.
Degree(s): B.S. in Biology from the University of Colorado Denver, 2012
Biography: Catherine is interested in studying the role of neuro-immunity in relation to neurodevelopmental disorders. As a PhD student in the Cowan Lab, Catherine is using mouse models to investigate the function of MEF2C in neurodevelopmental disorders through behavioral and molecular methods.
Degree(s): Ph.D. in Biological Sciences, Sechenov Institute of Evolutionary Physiology and Biochemistry
Biography: Evgeny studies cellular mechanisms of neuronal transmission at central nervous system synapses. In previous studies in the lateral nucleus of the amygdala, Evgeny described basic properties of long-term potentiation, long term depression, and established the nature of interactions between LTP and learned fear mechanisms. As an electrophysiologist in the Cowan Lab, Evgeny studies the effects of neurodevelopment genes on synaptic transmission and plasticity in multiple brain regions, including the cortex and hippocampus. He also studies the role of drug-regulated genes on synaptic plasticity in brain reward regions, including the nucleus accumbens and prefrontal cortex.
Degree(s): BS in Biology, University of North Texas; MMSc in Anesthesiology, Emory University
Biography: Ben received his Bachelor of Science in 2007 and Master of Medical Science in 2013. Ben has worked for the Cowan Lab since 2008 and assists with multiple facets of daily lab operation.
Cowan Lab Volunteers
Published, In Press or Accepted Original Research Papers
- Taniguchi, M., Carreira, M.B., Cooper, Y.A., Bobadilla, A.-C., Heinsbroek, J.A., Koike, N., Larson. E.B., Balmuth, E.A., Hughes, B.W., Penrod, R.D., Kumar, J., Smith, L.N., Guzman, D., Takahashi, J.S., Kim, T.-K., Kalivas, P.W., Self, D.W., Lin, Y., Cowan, C.W. HDAC5 and its target gene, NPAS4, regulate cocaine conditioned behaviors in the nucleus accumbens. Neuron, 2017, 96(1): 130 to 144. PMID: 28957664 (2017).
- Penrod, R.D., Carreira, M.B., Taniguchi, M., Kumar, J., Maddox, S.A., Cowan, C.W. Novel role and regulation of HDAC4 in cocaine-related behaviors. Addiction Biology, dol:10.1111/adb.12522 (2017).
- Harrington, A.J., Raissi, A., Kumar, J., Rajkovich, K., Raduazzo, J., Guo, Y., Loerwald, K., Huber, K.A., Cowan, C.W. MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders. eLife, 10.7554/eLife.20059 (2016).
- Robichaux, M.A., Chenaux, G., Ho, H.-Y.H., Soskis, M.J., Greenberg, M.E., Henkemeyer, M., Cowan, C.W. EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure. Dev. Neurobiology, 76(4): 405 to 420 (2016).
- Smith, L.N., Jedynak, J.P., Fontenot, M.R., Hale, C.F., Dietz, K.C., Taniguchi, M., Thomas, F.S., Zirlin, B.C., Birnbaum, S.G., Huber, K.M., Thomas, M.J., Cowan, C.W. Fragile X Mental Retardation Protein regulates synaptic and behavioral plasticity to repeated cocaine administration. Neuron, 82(3): 645 to 58 (2014). Video highlight for this article: Neuron online (2014)
- Robichaux, M.A., Chenaux, G., Ho, H.-Y.H., Soskis, M.J., Soskis, C., Kwan, K.Y., Sestan, N., Greenberg, M.E., Henkemeyer, M., Cowan, C.W. EphB receptor forward signaling regulates area-specific reciprocal thalamic and cortical axon guidance. Proc. Natl. Acad. Sci., USA, 111(6): 2188 to 93 (2014).
- Zang, T., Maksimova, M., Cowan, C.W., Bassel-Duby, R., Olson, E.N., Huber, K.M. Postsynaptic FMRP bi-directionally regulates excitatory synapses as a function of developmental age and MEF2 activity. Mol. Cell. Neurosci., 56: 39 to 49 (2013).
- Srivastava, N., Robichaux, M.A., Chenaux, G., Henkemeyer, M., Cowan, C.W. EphB receptor forward signaling controls cortical growth cone collapse via Nck and Pak. Mol. Cell. Neurosci., 52: 106 to 16 (2013).
- Tsai, N.-P., Wilkerson, J.R., Guo, W., Maksimova, M., DeMartino, G.N., Cowan, C.W., Huber, K.M. Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Cell, 151(7): 1581 to 94 (2012).
- Soskis, M.J., Ho, H.-Y. H., Bloodgood, B., Robichaux, M.R., Malik, A., Ataman, B., Rubin, A.A., Zhang, C., Shokat, K., Sharma, N., Cowan, C.W., Greenberg, M.E. A chemical genetic approach reveals a requirement for EphB Receptor tyrosine kinase activity in axon guidance but not synaptogenesis. Nature Neurosci., 15(12): 1645 to 54 (2012).
- Wang, Y., He, H., Srivastava, N., Vikarunnessa, S., Chen, Y.-B., Jiang, J., Cowan, C.W., Zhang, X. Plexins are GTPase Activating Proteins for Rap and are activated by induced dimerization. Science Signal., 5(207):ra6 (2012).
- Taniguchi, M., Carreira, M.B., Smith, L.N., Zirlin, B.C., Neve, R.L., Cowan, C.W. Histone Deacetylase 5 limits cocaine reward through cAMP-induced nuclear import. Neuron, 73(1): 108 to 20 (2012).
Preview for this article: West AE. Regulated Shuttling of the Histone Deacetylase HDAC5 to the Nucleus May Put a Brake on Cocaine Addiction. Neuron, 73(1), 1 to 2 (2012); Editors’ Choice for this article: Histone Deacetylates: Cocaine controls nuclear import. Sci. Signal., 5(207), ec18 (2012); Research Highlight for this article: Yates, D. “Addiction: Curtailing reward”, Nature Reviews Neurosci., 13: 151 (2012).
- Hale, C.F., Dietz, K.C., Varela, J.A., Wood, C.B., Zirlin, B.C., Leverich, L.S., Greene, R.W., Cowan, C.W. Essential role for Vav GEFs in brain-derived neurotrophic factor-induced dendritic spine growth and synapse plasticity. J. Neurosci., 31(35): 12426 to 12436 (2011).
- Pfeiffer, B.E., Zang, T., Wilkerson, J., Taniguchi, M., Maksimova, M.A., Smith, L.N., *Cowan, C.W., *Huber, K.M. Fragile X Mental Retardation Protein is required for synapse elimination by the activity-dependent transcription factor MEF2. Neuron, 66: 191 to 197 (2010). (*corresponding authors)
- Meyer, D.A., Richer, E., Benkovic, S.A., Hayashi, K., Kansy, J.W., Hale, C., Moy, L., Kim, Y., O’Callaghan, J.P., Tsai, L.-H., Greengard, P., Nairn, A.C., Cowan, C.W., Miller, D.B., Antich, P., Bibb, J.A. Striatal dysregulation of Cdk5 alters locomotor responses to cocaine, motor learning, and dendritic morphology. Proc. Natl. Acad. Sci., USA, 105: 18561 to 6 (2008).
- Pulliparacharuvil, S.G., Renthal, W., Hale, C.F., Taniguchi, M., Xiao, G., Kumar, A., Dewey, C.M., Davis, M., Nairn, A., Greengard, P., Nestler, E.J., Cowan, C.W. Cocaine regulates MEF2 to control synaptic and behavioral plasticity. Neuron, 59: 621 to 33 (2008).
“News and Views” on this article: Chandler LJ and Kalivas PW. Neuroscience: Brain’s defence against cocaine. Nature, 455: 743 to 4 (2008); “Research Highlights” on this article: Neuroscience, Coke Heads. Nature, 455: 5 (2008); “Research Findings” on this article: “Brain adaptation may dampen effects of cocaine”. NIDA Notes, (2010).
- Hunter, S.G., Zhuang, G., Brantley-Sieders, D., Swat, W., Cowan, C.W., Chen, J. Essential role of Vav family GEFs in EphA receptor-mediated angiogenesis. Mol. Cell Biol., 26: 4830 to 42 (2006).
- *Flavell, S.W., *Cowan, C.W., Kim, T.K., Greer, P.L., Lin, Y., Paradis, S., Griffith, E.C., Hu, L.S., Chen, C., Greenberg, M.E. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science, 311: 1008 to 12 (2006). (*authors contributed equally)
“Perspectives” on this article: Beg AA and Scheiffele P. Neuroscience: SUMO wrestles the synapse. Science, 311: 962 to 63 (2006); “Leading Edge” on this article: Neurobiology Select: Putting the brakes on synapse number. Cell, 125: 207 (2006).
- Cowan, C.W., Shao, Y.R., Sahin, M., Shamah, S.M., Lin, M.Z., Greer, P.L., Gao, S., Griffith, E.C., Brugge, J.S., Greenberg, M.E. Vav family GEFs link activated Ephs to endocytosis and axon guidance. Neuron, 46: 205 to 17 (2005).
Preview for this article: Murai KK and Pasquale EB. New exchanges in Eph-dependent growth cone dynamics. Neuron, 46: 161-3 (2005).
- Sahin, M., Greer, P.L., Lin, M.Z., O'Connell, S., Wright, T.M., Shamah, S.M., Eberhart, J., Cowan, C.W., Hu, L., Goldberg, J.L., Krull, C.E., Corfas, G., Greenberg, M.E. Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone collapse. Neuron, 46: 191 to 204 (2005).
- Sturla, L.-M., Cowan, C.W., Guenther, L., Castellino, R.C., Kim, J.Y.H., Pomeroy, S.L. A novel role for extracellular signal-regulated kinase 5 and myocyte enhancer factor 2 in medulloblastoma cell death. Cancer Res, 65: 5683 to 9 (2005).
- Datta, S.R., Ranger, A.M., Lin, M.Z., Sturgill, J.F., Ma, Y.C., Cowan, C.W., Dikkes, P., Korsmeyer, S.J., Greenberg, M.E. Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Dev. Cell, 3: 631 to 43 (2002).
- Kornhauser, J.M., Cowan, C.W., Shaywitz, A.J., Dolmetsch, R.E., Griffith, E.C., Hu, L.S., Haddad, C., Xia, Z., Greenberg, M.E. CREB transcriptional activity in neurons is regulated by multiple, calcium-specific phosphorylation events. Neuron, 34: 221 to 33 (2002).
Minireview for this article: Deisseroth, K. and Tsien, R.W. Dynamic multiphosphorylation passwords for activity-dependent gene expression. Neuron, 34:179 to 182 (2002).
- He, W., Melia, T.J., Cowan, C.W., Wensel, T.G. Dependence of RGS9-1 membrane attachment on its C-terminal tail. J. Biol. Chem., 276: 48961 to 6 (2001).
- Hu, G., Jang, G.-F., Cowan, C.W., Wensel, T.G., Palczewski, K. Phosphorylation of RGS9-1 by an endogenous protein kinase in rod outer segments. J. Biol. Chem., 276: 22287 to 95 (2001).
- Slep, K.C., Kerchner, M.A., He, W., Cowan, C.W., Wensel, T.G., Sigler, P.B. Structural determinants for regulation of phosphodiesterase by a G-protein at 2.0 angstroms. Nature, 409: 1071-7 (2001).
- He, F., Seryshev, A.B., Cowan, C.W., Wensel, T.G. Multiple zinc binding sites in retinal rod cGMP phosphodiesterase. J. Biol. Chem., 275: 20572 to 7 (2000).
- Rahman, Z., Gold, S.J., Potenza, M.N., Cowan, C.W., Ni, Y.G., He, W., Wensel, T.G., Nestler, E.J. Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene. J. Neurosci., 19: 2016-2026 (1999).
- Cowan, C.W., Farris, R.N., Sokal, I., Palczewski, K., Wensel, T.G. High expression levels in cones of RGS9, the predominant GTPase accelerating protein of rods. Proc. Natl. Acad. Sci., USA, 95: 5351 to 5356 (1998).
- *He, W., *Cowan, C.W., Wensel, T.G. RGS9, a GTPase accelerator for vision. Neuron, 20: 95 to 102 (1998). (*authors contributed equally)
Minireview for this article: Arshavsky VY and Pugh EN. Lifetime regulation of the G protein-effector complex: emerging importance of RGS proteins. Neuron, 20:11 to 14 (1998).
- Melia, T.J., Cowan, C.W., Angleson, J.K., Wensel, T.G. A comparison of the efficiency of G protein activation by ligand-free and light-activated forms of rhodopsin. Biophys. J., 73: 3182 to 3191 (1997).
- Adams, D.B., Cowan, C.W., Marshall, M.E., Stark, J. Competitive and territorial fighting: two types of offense in the rat. Physiol. Behav., 55: 247-54 (1994).
- Adams, D.B., Boudreau, W., Cowan, C.W., Kokonowski, C., Oberteuffer, K., Yohay, K.Offense produced by chemical stimulation of the anterior hypothalamus of the rat. Physiol. Behav., 53: 1127 to 1132 (1993).
Invited Book Chapters, Review Articles, Perspectives & Misc. Material
- Smith, L.N., Penrod, R.D., Taniguchi, M. and Cowan, C.W. Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice. J. Vis. Exp., 108 (2016). Invited Chapter.
- Penrod, R.D., Wells, A.M., Carlezon, Jr., W.A., Cowan, C.W. Use of Adeno-Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal Expression in Mice. Curr. Protoc. Neurosci., 73: 37.1 to 31 (2015). Invited Chapter.
- Cowan, C.W. Viewpoint: Misdirected neurons may underlie autism symptoms. Simons Foundation SFARI.org website (2014). Invited Perspective.
- Robichaux, M.A. and Cowan, C.W. Signaling Mechanisms of Axon Guidance and Early Synaptogenesis. Curr. Top. Behav. Neurosci. 16:19 to 48 (2014). Invited Book Chapter.
- Smith, L.N. and Cowan, C.W. News and Views: Striking a Balance in Fragile X. Nat. Medicine, 19(11): 1370 to 1 (2013). Invited Preview.
- Rothenfluh, A. and Cowan, C.W. The role of actin regulating proteins in drug-induced structural and behavioral plasticity: actin or reactin’. Curr. Opin. Neurobiol. 23(4): 507 to 12 (2013). Invited Perspective.
- Shen, K. and Cowan, C.W. Guidance Molecules in Synapse Formation and Plasticity. Neuronal Guidance: The Biology of Brain Wiring, Tessier-Lavigne, M. and Kolodkin, A.L. eds. Cold Spring Harbor Press, 311 to 328 (2010). Invited Book Chapter.
- Cowan, C.W., Hale, C.F., Taniguchi, M. Regulation of synaptic connectivity with chronic cocaine. Images in Neuroscience: Tamminga, C.A. ed. Am. J. Psychiatry, 165(11): 1393 (2008). Invited Perspective.
- Griffith, E.C., Cowan, C.W., Greenberg, M.E. REST acts through multiple deacetylase complexes. Neuron, 31: 339 to 40 (2001). Invited Preview.
- Cowan, C.W., He, W., Wensel, T.G. RGS proteins: lessons from the RGS9 subfamily and phototransduction. Prog. Nucleic Acid Res. Mol. Biol., 65: 341 to 59 (2000). Invited Review.
- Cowan, C.W., Wensel, T.G., Arshavsky, V.Y. Enzymology of GTPase acceleration in phototransduction. Methods Enzymol., 315: 524 to 38 (2000). Invited Chapter.