Stephen J. Haggarty, Ph.D.
Stephen J. Haggarty, Ph.D., is an Associate Professor of Neurology at Harvard Medical School, an Associate in Neuroscience at Massachusetts General Hospital (MGH), Director of the Chemical Neurobiology Laboratory (CGL) within the MGH Center for Human Genetic Research (CHGR), and a Senior Associate member of the Broad Institute of Harvard & MIT. He also serves at the Head of Neuropharmacology for the MGH Psychiatry Center for Experimental Drugs & Diagnostics (CEDD). Dr. Haggarty received his Ph.D. from Harvard University. Dr. Haggarty then joined the Broad Institute as a research Fellow in the Chemical Biology Program before joining the faculty at Harvard Medical School and the Molecular Neurogenetics and Psychiatric Neurodevelopmental Genetics Units at MGH.
Dr. Haggarty’s research program focuses on the use of chemistry and genetics to define and dissect the role of neuroplasticity in health and disease. His long-term goal is to translate this knowledge into the discovery of novel, disease mechanism-based, targeted therapeutics for neuropsychiatric disorders.
Members of the Haggarty Laboratory & CGL have developed powerful, in vitro experimental systems in which populations of defined neuronal subtypes belonging to specific neurotransmitter classes and regional identities with the ability to form synapses and electrically active, neural networks, can be directly identified, manipulated pharmacologically and genetically, and characterized using functional genomics, proteomics, and high-throughput screening modalities. This has lead to the discovery, characterization, and optimization of novel chemical probes of critical neuroplasticity mechanisms—the regulation of neurotrophic factor signaling, the epigenetic regulation of neuronal gene expression through histone deacetylases (HDACs) and histone demethylases (HDMs), and the regulation of Wnt/GSK3 signaling. To address the challenge of target identification, systematic RNAi-mediated gene silencing and quantitative mass spectrometry strategies have been implemented in the context of cultured neurons. To explore new directions for human disease modeling, the CGL has implemented reprogramming methods for creating induced pluripotent stem cells (iPSCs) and induced neurons (iNs) from patient-derived, somatic cells. These iPSCs 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 chemical genomic studies of neuroplasticity and for understanding human disease biology. On-going translational efforts include in vivo testing of novel pharmacological probes using animal behavioral models relevant to cognitive and mood disorders, as well as with positron emission tomography to image targets and neural activity in the context of intact neurocircuits. Finally, in collaboration with clinical colleagues in Psychiatry and the CEDD, experimental therapeutic trials are underway to test therapeutic hypotheses in conjunction with the generation of patient-specific stem cell models to correlate drug efficacy and ex vivo response of cultured neurons.
We conduct our research program in close collaboration with other members of the Harvard and MIT research community, including the MGH Molecular Neurogenetics Unit, MGH Psychiatric & Neurodevelopmental Genetics Unit, MGH Center for Experimental Drugs & Diagnostics, Lurie Center for Autism, Stanley Center for Psychiatric Research at the Broad Institute, and the Harvard Stem Cell Institute.