Area of Research
Synapses and Circuits, Models of Psychiatric Disorders, Neurogenetics
Genetics and Animal Models of Complex Psychiatric Disorders; assembly and maintenance of sensory maps in the brain.
The goal of our research is to understand the nature of the genetic deficits that predispose to psychiatric disorders (especially schizophrenia) and trace the affected biological pathways. Ultimately, we would like to provide novel targets for pharmacotherapy for these disorders. Toward these goals, 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 especially on the contribution of rare mutations in the genetic architecture of complex psychiatric disorders.
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 and biological complexity of psychiatric disorders is the major component of my lab and has contributed a series of recent discoveries.
iii. Sensory Processing in Psychiatric Disorders: We are interested in understanding the deficits of sensory processing in psychiatric diseases and elucidating the genetic and biological basis of these deficits. For example, 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 sensory circuit assembly under competition, 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.
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.
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.