Joseph Gogos, M.D.
Professor of Physiology & Cellular Biophysics , and Neuroscience
Member Zuckerman Mind Brain Behavior Institute
Genetics and Animal Models of Complex Psychiatric Disorders
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:
(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. Our genetics program has contributed a series of genetic discoveries especially on the contribution of rare mutations in the genetic architecture of schizophrenia.
(II) 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.
Recapitulation and Reversal of Schizophrenia-Related Phenotypes in Setd1a-Deficient Mice. Mukai J, Cannavò E, Crabtree GW, Sun Z, Diamantopoulou A, Thakur P, Chang CY, Cai Y, Lomvardas S, Takata A, Xu B, Gogos JA Neuron.2019 Nov 6
Age-Dependent Specific Changes in Area CA2 of the Hippocampus and Social Memory Deficit in a Mouse Model of the 22q11.2 Deletion Syndrome. Piskorowski RA, Nasrallah K, Diamantopoulou A, Mukai J, Hassan SI, Siegelbaum SA, Gogos JA, Chevaleyre V Neuron. 2016 Jan 6
Molecular substrates of altered axonal growth and brain connectivity in a mouse model of schizophrenia. Mukai J, Tamura M, Fénelon K, Rosen AM, Spellman TJ, Kang R, MacDermott AB, Karayiorgou M, Gordon JA, Gogos JA Neuron. 2015 May 6
Loss-of-function variants in schizophrenia risk and SETD1A as a candidate susceptibility gene. Takata A, Xu B, Ionita-Laza I, Roos JL, Gogos JA, Karayiorgou M Neuron.2014 May 21
Derepression of a neuronal inhibitor due to miRNA dysregulation in a schizophrenia-related microdeletion. Xu B, Hsu PK, Stark KL, Karayiorgou M, Gogos JA Cell.2013 Jan 17