Chemical Neurobiology Laboratory (CNL)
Since its inception in 2006, the Chemical Neurobiology Laboratory (CNL) has specialized in the development of neuronal cell-based assays to support high-throughput chemical screening and the investigation of candidate disease gene function using multi-parametric automated microscopy, laser scanning cytometry, along with functional genomic, biochemical, and proteomic techniques. These assays have allowed the laboratory to investigate the response of neuronal cells to thousands of different chemical probes and have led to the discovery, characterization, and optimization of novel chemical probes of critical neuroplasticity processes—the regulation of neurotrophic factor signaling, the epigenetic regulation of neuronal gene expression, and the regulation of Wnt/GSK3 signaling.
Through collaborations with members of the Harvard, MIT, and Broad research community, the Haggarty laboratory has begun to investigate the effects of targeting these new molecular mechanisms on memory and mood using rodent behavioral models relevant to cognition and affective behavior, as well as the use of positron emission tomography (PET) imaging for assessing compound distribution and effect on neurocircuitry.
The Haggarty laboratory has also been at the forefront of the application of methods for generating patient-specific stem cell models of neuropsychiatric disorders using reprogramming technology. These stem cells can be differentiated in vitro into functional neurons with the capacity to form synapses and regulate genes in an activity-dependent manner opening new avenues for studies of neuroplasticity and neuropharmacology. In addition to generating new patient-specific stem cell models, we aim to advance a platform for human experimental neurobiology and novel therapeutic discovery based around the use of stem-cell human neurons for functional genomic studies in combination with high-throughput screening.