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Chris Risher

Chris Risher, PhD
Assistant Professor

Research Interest

In the past decade, much progress has been made towards understanding how neurons, the cells responsible for the processing and transfer of information in the central nervous system (CNS), interact with non-neuronal brain cells. However, there is still a lack of information about how non-neuronal cells contribute to the structural and functional maturation of the neuronal junctions known as synapses. Our work focuses on identifying and elaborating the genes, molecules, and signaling pathways that are crucial for linking non-neuronal cells with the synaptic structures that have been shown to be severely disrupted in nearly all known neurodevelopmental and psychiatric disorders. The long-term goal of our research is to contribute to novel therapeutic strategies to prevent or repair the impaired synaptic connectivity that occurs during abnormal brain development and following CNS injury or insult. My previous findings led me to postulate that the formation and maturation of synapses and dendritic spines, the mushroom-like protrusions that receive excitatory synaptic contact, are not entirely neuron-intrinsic processes. Using a wide array of techniques including transgenic mouse lines, in vitro and ex vivo culture systems, and three-dimensional reconstructions of spines and synapses in the mouse brain at the highest level of resolution, I have determined that multiple stages of synaptic development are highly regulated by astrocytes, the most abundant glial cell type in the brain. Going forward, I believe that understanding the complex relationships between astrocytes, spines, and synapses will be key to forging new therapies for brain disorders characterized by aberrant synaptic connectivity, including autism, schizophrenia, and addiction.

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  1. Regulation of synaptic development by astrocyte signaling factors and their emerging roles in substance abuse. Walker CD, Risher WC, Risher ML. 2020. Cells 9(2): E297. PMID: 31991879
  2. Thrombospondin receptor alpha-2-delta-1 promotes synaptogenesis and spinogenesis via postsynaptic Rac1. Risher WC, Kim N, Koh S, Choi JE, Mitev PR, Spence EF, Pilaz LJ, Wang D, Feng G, Silver DL, Soderling SH, Yin HH, Eroglu C. 2018.  J Cell Bio 217(10): 3747-65. PMCID: PMC6168259
  3. Adolescent Intermittent Alcohol Exposure: Dysregulation of Thrombospondins and Synapse Formation are Associated with Decreased Neuronal Density in the Adult Hippocampus. Risher ML, Sexton HG, Risher WC, Wilson WA, Fleming RL, Madison RD, Moore SD, Eroglu C, Swartzwelder HS. 2015.  Alcohol Clin Exp Res 39(12): 2403-13. PMCID: PMC4712076
  4. Adolescent intermittent alcohol exposure: Persistence of a structural and functional hippocampal abnormalities into adulthood. Risher ML, Fleming RL, Risher WC, Miller KM, Klein RC, Wills T, Acheson SK, Moore SD, Wilson WA, Eroglu C, Swartzwelder HS. 2015. Alcohol Clin Exp Res 39(6): 989-97. PMCID: PMC4452443
  5. Astrocytes refine cortical connectivity at dendritic spines. Risher WC, Patel S, Kim IH, Uezu A, Bhagat S, Wilton DK, Pilaz LJ, Singh Alvarado J, Calhan OY, Silver DL, Stevens B, Calakos N, Soderling S, Eroglu C. 2014. eLife 3:e04047. PMCID: PMC4286724.
  6. Rapid Golgi analysis method for efficient and unbiased classification of dendritic spines. Risher WC, Ustunkaya T, Singh Alvarado J, Eroglu C. 2014. PLOS ONE 9(9):e107591. PMCID: PMC4160288.
  7. Huntingtin is required for normal excitatory synapse development in cortical and striatal circuits. McKinstry SU, Karadeniz YB, Worthington AK, Hayrapetyan VY, Ozlu MI, Serafin-Molina K, Risher WC, Ustunkaya T, Dragatsis I, Zeitlin S, Yin HH, Eroglu C. 2014. J. Neurosci 34(28): 9455-72. PMCID: PMC4087216.
  8. Persistent astroglial swelling accompanies rapid reversible dendritic injury during stroke-induced spreading depolarizations. Risher WC, Croom D, Kirov SA. 2012. Glia 60(11): 1709-20. PMCID: PMC3435464.
  9. Thrombospondins as key regulators of synaptogenesis in the central nervous system. Risher WC, Eroglu C. 2012. Matrix Biology 31(3): 170-7. PMCID: PMC3961754.
  10. Dibucaine mitigates spreading depolarization in human neocortical slices and prevents acute dendritic injury in the ischemic rodent neocortex. Risher WC, Lee MR, Hess DC, Kirov SA. 2011. PLOS ONE 6(7): e22351. PMCID: PMC3137632.
  11. Recurrent spontaneous spreading depolarizations facilitate acute dendritic injury in the ischemic penumbra. Risher WC, Ard D, Yuan J, Kirov SA. 2010. J. Neurosci 30(29): 9859-68. PMCID: PMC2918261.
  12. Real-time passive volume responses of astrocytes to acute osmotic and ischemic stress in cortical slices and in vivo revealed by two-photon microscopy. Risher WC, Andrew RD, Kirov SA. 2009. Glia 57(2): 207-21. PMCID: PMC2635108.
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