Joseph A. Gogos, MD, PhD

Profile Headshot

Overview

Academic Appointments

  • Professor of Physiology & Cellular Biophysics and Neuroscience
  • Professor of Neuroscience

Languages

  • Greek

Gender

  • Male

Credentials & Experience

Education & Training

  • MD, Medicine, National University of Athens Faculty of Medicine (Greece)
  • PhD, Molecular Biology, Harvard University

Research

My laboratory has elucidated the contribution of rare de novo and inherited mutations to the genetic risk of schizophrenia and develops relevant model systems to understand their impact on neural mechanisms and advance neuropsychiatric therapeutics. Some of the questions we try to answer are: What kind and how many different mutations increase the risk for schizophrenia? What kind of failures in neural circuits in our brain underlie these constellation of symptoms we refer to as schizophrenia? Why do neural circuits fail in particular ways and not others when our genetic program is disturbed by disease mutations? Why are conditions such as schizophrenia so frequent? Toward these goals, my laboratory has two interconnected research programs:

• Genetics of Complex Psychiatric Disorders: Most psychiatric disorders have a strong genetic component and, therefore, our starting point is findings from human genetic approaches. Our genetics program has contributed a series of genetic discoveries especially on the contribution of rare mutations in the genetic architecture of schizophrenia.

• Animal Models of Complex Psychiatric Disorders: We are using mouse models of rare, recurrent, large-effect mutations to 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 a range of state-of-the-art approaches to dissect the biological complexity of schizophrenia is the major component of my lab and has contributed a series of recent discoveries.

Research Interests

  • Neurogenetics
  • Models of Psychiatric Disorders
  • Synapses and Circuits
  • Neurobiology of Disease

Grants

MICRORNA DYSREGULATION IN PYSCHIATRIC DISORDERS AND COGNITIVE DYSFUNCTION (Federal Gov)

Aug 15 2017 - Jun 30 2022

IDENTIFYING TREATMENT TARGETS: EXPLORING AND EXPLOITING NEURAL MECHANISMS OF COGNITIVE DEFICITS IN THE 22Q11.2 MICRODELETION (Federal Gov)

Aug 1 2017 - Apr 30 2022

DECIPHERING THE ROLE OF HISTONE METHYLTRANSFE (Federal Gov)

Mar 1 2017 - Feb 28 2022

THE ROLE OF THE HIPPOCAMPAL CA2 REGION IN NEUROPSYCHIATRIC DISEASE (Federal Gov)

Dec 14 2015 - Nov 30 2020

FUNCTIONAL ANALYSIS OF THE 22Q11.2 SCHIZOPHRENIA SUSCEPTIBILITY GENES (Federal Gov)

Dec 1 2002 - Apr 30 2020

VPAC2 RECEPTOR FUNCTION AND ITS LINK TO SCHIZOPHRENIA (Federal Gov)

Apr 1 2015 - Mar 31 2019

ELUCIDATING THE EFFECT OF DISC 1 ON NEURODEVELOPMENT AND SYNAPTIC TRANSMISSION (Federal Gov)

Jul 15 2007 - Sep 30 2017

THE ROLE OF GABA-MIMETIC METABOLITES IN NEURODEVELOPMENTAL AND NEUROPSYCHIATRIC DISORDERS (Federal Gov)

Jun 11 2013 - Sep 30 2015

IPS CELL-DERIVED NEURONS CARRYING AN ALLELIC SERIES OF CNTNA P2 STRUCTURAL MUTATIONS (Federal Gov)

Sep 30 2009 - Aug 31 2012

UNDERSTANDING THE GENOMIC RISK ARCHITECTURE OF SCHIZOPHRENIA USING GENE EXPRESSION ANALYSIS IN MODEL SYSTEMS (Federal Gov)

Sep 30 2009 - Aug 31 2012

GENOMIC IMBALANCES AT THE 22Q11 LOCUS AND PREDISPOSITION TO AUTISM (Private)

Jul 1 2008 - Jun 30 2012

ELECTROPHYSIOLOGY CHARACTERIZATION OF THE DENTATE GYRUS IN D ISC 1 MUTANT MOUSE MODEL OF SCHIZOPHRENIA (Private)

Jan 1 2010 - Dec 31 2011

THE CONTRIBUTION OF ABNORMAL MICRORNA BIOGENESIS TO THE PSYC HIATRIC SYMPTOMS OF 2Q11 DELETION SYNDRO (Private)

Jul 1 2008 - Jun 30 2010

HIPPOCAMPAL STRUCTURE & FUNCTION IN A BDNF VAL66MET KNOCK-IN MOUSE STRAIN. (Private)

Jul 1 2006 - Jun 30 2008

Selected Publications

Hamm JP, Peterka DS, Gogos JA, Yuste R. Altered Cortical Ensembles in Mouse Models of Schizophrenia. Neuron. 2017 Apr 5;94(1):153-167.e8. doi: 10.1016/j.neuron.2017.03.019.

Crabtree GW, Sun Z, Kvajo M, Broek JA, Fénelon K, McKellar H, Xiao L, Xu B, Bahn S, O'Donnell JM, Gogos JA. Alteration of Neuronal Excitability and Short-Term Synaptic Plasticity in the Prefrontal Cortex of a Mouse Model of Mental Illness. J Neurosci. 2017 Apr 12;37(15):4158-4180. doi: 10.1523/JNEUROSCI.4345-15.2017. Epub 2017 Mar 10.

Crabtree GW, Park AJ, Gordon JA, Gogos JA. Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade. Cell Rep. 2016 Oct 4;17(2):570-582. doi: 10.1016/j.celrep.2016.09.029.

Tamura M, Mukai J, Gordon JA, Gogos JA. 2016 Developmental Inhibition of Gsk3 Rescues Behavioral and Neurophysiological Deficits in a Mouse Model of Schizophrenia Predisposition. Neuron 89:1100-1109.

Piskorowski RA, Nasrallah K, Diamantopoulou A, Mukai J, Hassan SI, Siegelbaum SA, Gogos JA, Chevaleyre V. 2016 Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome. Neuron 89:163-176.

Mukai J, Tamura M, Fénelon K, Rosen AM, Spellman TJ, Kang R, MacDermott AB, Karayiorgou M, Gordon JA, Gogos JA. 2015 Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia. Neuron 86:680-695.

Takata A, Xu B, Ionita-Laza I, Roos JL, Gogos JA, Karayiorgou M. 2014 Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene. Neuron 82:773-780.

Fénelon K, Xu B, Lai CS, Mukai J, Markx S, Stark KL, Hsu PK, Gan WB, Fischbach GD, MacDermott AB, Karayiorgou M, Gogos JA. 2013 The pattern of cortical dysfunction in a mouse model of a schizophrenia-related microdeletion. J Neurosci. 33:14825-14839.

Xu B, Hsu PK, Stark KL, Karayiorgou M, Gogos JA. 2013 Derepression of a Neuronal Inhibitor due to miRNA Dysregulation in a Schizophrenia-Related Microdeletion Cell 152:262-275.

Xu B, Ionita-Laza I, Roos JL, Boone B, Woodrick S, Sun Y, Levy S, Gogos JA, Karayiorgou M. 2012 De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia. Nat Genet. 44:1365-1369.

Sigurdsson T, Stark KL, Karayiorgou M, Gogos JA, Gordon JA. 2010 Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. Nature 464:763-767.


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. 11:1302-1310.



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. 40:880-885.



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. 40:751-760.

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. 8:1586-1594.