F A C U L T Y P R O F I L E
GOGOS, JOSEPH A., M.D., Ph.D.
Genetics and Animal Models of Complex Psychiatric Disorders; assembly and maintenance of sensory maps in the brain.
Office: Physicians & Surgeons | 11th floor | Room 519
The goal of our research is two-fold: first, to understand the nature of the genetic deficits that predispose to psychiatric disorders (especially schizophrenia) and trace the affected biological pathways and second, to provide novel targets for pharmacotherapy for these disorders. Toward this goal, my lab has three interconnected research programs;
i. Genetics of Complex Psychiatric Disorders: Most psychiatric disorders have a strong genetic component and, therefore, our starting point is findings from human genetic approaches. This component interacts closely with Dr. Karayiorgou’s lab at the Department of Psychiatry, Columbia University and has contributed a series of genetic discoveries using state-of-the-art techniques and genetic material from an extensive and powerful set of afflicted families collected over the past 10 years by Dr. Karayiorgou and her colleagues.
ii. Animal Models of Complex Psychiatric Disorders: We take advantage of human genetic findings that stand on firm ground and the reductive power of forward mouse genetics and ask what are the consequences of a genetic lesion associated with mental illness in humans, on brain structure and function of a model organism, starting at the simpler cellular and synaptic levels to the higher-order circuit and behavior levels. Implementation of iterative human and mouse genetic approaches to dissect the genetic complexity of psychiatric disorders is the major component of my lab and has contributed a series of recent discoveries.
iii. Animal Models of neural activity-dependent competition: We are interested in understanding the deficits of sensory processing in psychiatric diseases and elucidating the genetic basis of these deficits. One goal of this component of my work is to describe the phenomenology of activity-based competition and identify the largely unknown molecular pathways that modulate neural circuit assembly in competitive environments, which are often imposed by a changing environment or a disease state.
Sigurdsson T, Stark KL, Karayiorgou M, Gogos JA, Gordon JA. 2010 Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. Nature. 464:763-7.
Arguello PA, Gogos JA. 2010 Cognition in mouse models of schizophrenia susceptibility genes. Schizophr Bull. 36, 289-300.
Xu B, Karayiorgou M, Gogos JA. 2010 microRNAs in Psychiatric and Neurodevelopmental Disorders. Brain Res. [Epub ahead of print]
Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L, Macdermott AB, Karayiorgou M, Gogos JA. 2008 Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat Neurosci. 11:1302-10
Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. 2008. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet. 40:880-5.
Stark KL, Xu B, Bagchi A, Lai WS, Liu H, Hsu R, Wan X, Pavlidis P, Mills AA, Karayiorgou M, Gogos JA. 2008. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet. 40:751-60.
Kvajo M, McKellar H, Arguello PA, Drew LJ, Moore H, MacDermott AB, Karayiorgou M, Gogos JA. 2008. A mutation in mouse Disc1 that models a schizophrenia risk allele leads to specific alterations in neuronal architecture and cognition. Proc Natl Acad Sci U S A 105:7076-81.
Yavich L, Forsberg MM, Karayiorgou M, Gogos JA, Männistö PT. 2007. Site-specific role of catechol-O-methyltransferase in dopamine overflow within prefrontal cortex and dorsal striatum. J Neurosci. 27:10196-209.
Cao L, Dhilla A, Mukai J, Blazeski R, Lodovichi C, Mason CA, Gogos JA. 2007. Genetic modulation of BDNF signaling affects the outcome of axonal competition in vivo. Curr Biol. 17:911-21.
Lai WS, Xu B, Westphal KG, Paterlini M, Olivier B, Pavlidis P, Karayiorgou M, Gogos JA. 2006. Akt1 deficiency affects neuronal morphology and predisposes to abnormalities in prefrontal cortex functioning. Proc Natl Acad Sci U S A 103:16906-11.
Arguello PA, Gogos JA. 2006. Modeling madness in mice: one piece at a time. Neuron 52:179-96.
Koike H, Arguello PA, Kvajo M, Karayiorgou M, Gogos JA. 2006. Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice. Proc Natl Acad Sci U S A 103:3693-7.
Paterlini M, Zakharenko SS, Lai WS, Qin J, Zhang H, Mukai J, Westphal KG, Olivier B, Sulzer D, Pavlidis P, Siegelbaum SA, Karayiorgou M, Gogos JA. 2005.Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice. Nat Neurosci. 8:1586-94.
Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M, Gogos JA. 2004. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet. 36:725-31.
Yu CR, Power J, Barnea G, O'Donnell S, Brown HE, Osborne J, Axel R, Gogos JA. 2004. Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron 42:553-66.
Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. 2004. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet. 36:131-7.