David A. Lewis, M.D.
Distinguished Investigator

Dr. Lewis is the UPMC Endowed Professor of Translational Neuroscience, Professor of Psychiatry and Neuroscience, and Director of the Translational Neuroscience Program at the University of Pittsburgh. He also serves as Director of an NIMH Conte Center for the Neuroscience of Mental Disorders, which is focused on understanding the role of prefrontal cortical dysfunction in the pathophysiology of schizophrenia. He received his medical degree from The Ohio State University, completed residencies in internal medicine and in psychiatry at the University of Iowa, and received his research training at the Research Institute of the Scripps Clinic. Dr. Lewis has published over 285 scientific articles. He has received NIMH Senior Scientist and MERIT Awards, is a Fellow in both the American College of Neuropsychopharmacology and the American College of Psychiatrists, is a member of the Institute of Medicine of the National Academy of Sciences, and serves on the Scientific Council for NARSAD, on the Council of the American College of Neuropsychopharmacology and on the National Mental Health Advisory Council. He is also a Deputy Editor of The American Journal of Psychiatry. Recognition of Dr. Lewis’ research accomplishments has included the Lieber Prize for Schizophrenia Research from NARSAD, the William K. Warren Award from the International Congress of Schizophrenia Research, and the Stanley Dean Research Award from the American College of Psychiatrists.

Dr. Lewis’ research activities focus on the neural circuitry of the prefrontal cortex and related brain regions, and the alterations of this circuitry in schizophrenia. The research strategy underlying these investigations involves several components. First, the normal functional architecture of the prefrontal cortex, including its connections with other cortical and subcortical regions, is examined using the macaque monkey as a model system for the human brain. Within these circuits, the expression and cellular localization of specific gene products, and how these change in an activity-dependent fashion, are investigated. The electrophysiological properties of intrinsic prefrontal cortical circuits are studied using an in vitro slice preparation. Second, the postnatal development of prefrontal cortical circuitry is characterized, with special emphasis placed on maturational events, such as synaptogenesis and synaptic pruning, which occur during early postnatal life and adolescence. The timing and specificity of these processes are examined for their possible contribution to the emergence and refinement of the types of cognitive abilities that are disturbed in schizophrenia. Third, based on the results of these lines of investigation, hypotheses are generated regarding the elements of neural circuitry that may be dysfunctional in schizophrenia. These hypotheses are then tested in postmortem human brain specimens from subjects with schizophrenia. Fourth, the primate model system is used to assess the influence of psychotropic medications on the neural circuits of interest, and mouse genetic models are used as “proof of concept” tests of the cause-effect relationships between the alterations observed in the disease state. The goal of these studies is to define the pathogenetic mechanisms and pathophysiological processes that give rise to the cognitive deficits of schizophrenia. Finally, these findings are used to identify potential targets for novel therapeutic interventions that are examined in Phase II clinical trials.

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