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The Daniel Weinberger Laboratory focuses on the neurobiological mechanisms of genetic risk for developmental brain disorders. We study the genetic regulation of the transcriptome in normal human brain across the human life span and in brains from patients with various psychiatric disorders. We also study the impact of genetic variation on aspects of human brain development and function linked with risk for schizophrenia and related psychiatric disorders. Our lab uses unique molecular and clinical datasets and biological materials from a large sample of families with affected and unaffected offspring and normal volunteers. These datasets include DNA, lymphoblast and fibroblast cell lines, and extensive quantitative phenotypes related to genetic risk for schizophrenia, including detailed cognitive assessments and various neuroimaging assays. In other research, we are working on a human brain transcriptome project that is RNA sequencing over 1,000 human brain samples in various regi...ons and based also on sorting of specific celliular phentypes. We are exploring the molecular processing of the gene and its implications for cognition and aspects of human temperament. view more
Schizophrenia, autism and other neurological disorders are caused by a complex interaction between inherited genetic risk and environmental experiences. The overarching goal of the group are to reveal molecular mechanisms of gene by environment interactions related to altered neural development and liability for brain disorders. Our research uses a hybrid of human stem cell models, post-mortem tissue and computational approaches to interrogate the contribution of epigenetic regulation and somatic mosaicism to brain diseases. Our previous work has demonstrated that the human brain exhibits extensive genetic variability between neurons within the same brain, termed "somatic mosaicism" due to mobile DNA elements which mediate large somatic DNA copy number variants. We study environment-responsive mechanisms and consequences for somatic mosaicism and are discovering the landscape of somatic mosaicism in the brain. We also study the epigenetic regulation of cell specification and activity-d...ependent states within the human dorsal lateral prefrontal cortex and striatum. view more
Healthy Brain Program
The Brain Health Program is a multidisciplinary team of faculty from the departments of neurology, psychiatry, epidemiology, and radiology lead by Leah Rubin and Jennifer Coughlin. In the hope of revealing new directions for therapies, the group studies molecular biomarkers identified from tissue and brain imaging that are associated with memory problems related to HIV infection, aging, dementia, mental illness and traumatic brain injury. The team seeks to advance policies and practices to optimize brain health in vulnerable populations while destigmatizing these brain disorders.
Current and future projects include research on: the roles of the stress response, glucocorticoids, and inflammation in conditions that affect memory and the related factors that make people protected or or vulnerable to memory decline; new mobile apps that use iPads to improve our detection of memory deficits; clinical trials looking at short-term effects of low dose hydrocortisone and randomized to 28 day...s of treatment; imaging brain injury and repair in NFL players to guide players and the game; and the role of inflammation in memory deterioration in healthy aging, patients with HIV, and other neurodegenerative conditions. view more