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The Brady Maher Laboratory is interested in understanding the cellular and circuit pathophysiology that underlies neurodevelopmental and psychiatric disorders. Our lab focuses on trying to understand the function of genes that are associated with neurodevelopment problems by manipulating their expression level in utero during the peak of cortical development. We then use a variety of approaches and technologies to identify resulting phenotypes and molecular mechanisms including cell and molecular biology, optogenetics, imaging and electrophysiology.
Current projects in the lab are focused on understanding the function of transcription factor 4 (TCF4), a clinically pleiotropic gene. Genome-wide association studies have identified genetic variants of TCF4 that are associated with schizophrenia, while autosomal dominant mutations in TCF4 result in Pitt Hopkins syndrome. Using our model system, we have identified several interesting electrophysiological and cell biological phenotypes as...sociated with altering the expression of TCF4 in utero. We hypothesize that these phenotypes represent cellular pathophysiology related to these disorders and by understanding the molecular mechanisms responsible for these phenotypes we expect to identify therapeutic targets for drug development.
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The Brown Lab is focused on the function of the cerebral cortex in the brain, which underlies our ability to interact with our environment through sensory perception and voluntary movement. Our research takes a bottom-up approach to understanding how the circuits of this massively interconnected network of neurons are functionally organized, and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders, including autism and schizophrenia. By combining electrophysiological and optogenetic approaches with anatomical and genetic techniques for identifying cell populations and pathways, the Brown Lab is defining the synaptic interactions among different classes of cortical neurons and determining how long-range and local inputs are integrated within cortical circuits. In amyotrophic lateral sclerosis, corticospinal and spinal motor neurons progressively degenerate. The Brown Lab is examining how abnormal ...activity within cortical circuits contributes to the selective degeneration of corticospinal motor neurons in an effort to identify new mechanisms for treating this disease. Abnormalities in the organization of cortical circuits and synapses have been identified in genetic and anatomical studies of neuropsychiatric disease. We are interested in the impact these abnormalities have on cortical processing and their contribution to the disordered cognition typical of autism and schizophrenia. view more
The Dölen lab studies the synaptic and circuit mechanisms that enable social behaviors. We use a variety of techniques including whole cell patch clamp electrophysiology, viral mediated gene transfer, optogenetics, and behavior. We are also interested in understanding how these synaptic and circuit mechanisms are disrupted in autism and schizophrenia, diseases which are characterized by social cognition deficits. More recently we have become interested in the therapeutic potential of psychedelic drugs for diseases like addiction and PTSD that respond to social influence or are aggravated by social injury, We are currently using both transgenic mouse and octopus to model disease.
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