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 regions 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.

Andreia Faria's Laboratory focuses on investigating brain functions using MRIs. We develop and apply methods for processing and analyzing diverse MRI modalities in order to characterize distinctive brain patterns and to study multiple conditions, including neurodegenerative diseases, psychiatric disorders, and stroke. We use artificial intelligence to develop tools for brain MRI segmentation and quantification, promoting the means to perform reliable and reproducible translational research.

Dr. Ross and his research team have focused on Huntington's disease and Parkinson's disease, and now are using insights from these disorders to approach more complex diseases such as schizophrenia and bipolar disorder. They use biophysical and biochemical techniques, cell models, and transgenic mouse models to understand disease processes, and to provide targets for development of rational therapeutics. These then can provide a basis for developing small molecule interventions, which can be used both as probes to study biology, and if they have favorable drug-like properties, for potential therapeutic development. We have used two strategies for identifying lead compounds. The first is the traditional path of identification of specific molecular targets, such as enzymes like the LRRK2 kinase of Parkinson’s disease. Once structure is known, computational approaches or fragment based lead discovery, in collaboration, can be used. The second is to conduct phenotypic screens using cell models, or in a collaboration, natural products in a yeast model. Once a lead compound is identified, we use cell models for initial tests of compounds, then generate analogs, and take compounds that look promising to preclinical therapeutic studies in animal models. The ultimate goal is to develop therapeutic strategies that can be brought to human clinical trials, and we have pioneered in developing biomarkers and genetic testing for developing strategies.

Research in the Joseph Gallo Lab focuses on the form and course of depression in older adults; treatment in primary care settings; the use of mixed methods in health services research; and the epidemiology of psychiatric disorders in the population. Using NIMH Epidemiologic Catchment Area survey data, we have conducted studies using novel statistical modeling (the MIMIC model) to explore how depression presents differently among older adults versus younger people. We are taking part in the long-term follow-up of PROSPECT (Prevention of Suicide in Primary Care Elderly – Collaborative Trial) — a randomized study of depression management in primary care practices — and have examined mortality as an outcome in the context of medical comorbidity.