Structure of the Conte Center
The Center is composed of an Administrative Core plus two scientific cores and four scientific projects. The Director of the Center is Dr. Eric Nestler.
- Administrative Core (PI, Eric Nestler; Mount Sinai). The Administrative Core is responsible for the oversight of the Center and for coordinating and integrating the Center’s many diverse research activities.
- The Animal Models Core (PI, Venetia Zachariou, Scott Russo, Ming-Hu Han; Mount Sinai) pprovides a uniquely broad array of mouse depression models in females and males as well as an impressive arsenal of molecular tools (viral vectors, genetic mutant mice, neurophysiological recordings, optogenetics, fiber photometry) used to characterize molecular mechanisms in these models. Other key faculty include Rachael Neve at MIT. For further information, see Scientific Tools.
- The Chromatin and Gene Analysis Core (PI, Eric Nestler, Li Shen; Anne Schaefer, Mount Sinai) provides state-of-the-art methods to analyze gene expression and chromatin modifications within discrete brain regions in an open-ended genome-wide manner, along with the advanced bioinformatic tools necessary to effectively mine the enormous datasets derived. For further information, see Scientific Tools.
- Project 1 (PI, Eric Nestler; Mount Sinai) is focused on transcriptional and epigenetic mechanisms in the nucleus accumbens (NAc) and ventral tegmental area (VTA), key brain reward regions implicated in depression and other stress-related disorders. Current studies are concentrating on mechanisms by which early life stress controls stress susceptibility vs. resilience for a lifetime. Sex differences in such mechanisms are a major theme of ongoing research.
- Project 2 (PI, Schahram Akbarian; Mount Sinai) is focused on stress regulation of the 3-dimensional (3D) structure of chromatin within neurons of the prefrontal cortex, also crucial for stress responses, The team has demonstrated that stress produces profound changes in chromosomal loopings, with particular regulation seen at the protocadherin gene locus, and uses novel experimental approaches to study such loopings over the lifetime of an individual.
- Project 3 (PI, David Allis, Rockefeller; Ian Maze, Mount Sinai) is focused on the role of histone substitution in depression and antidepressant action. In addition to covalently modifying histones and DNA, we now know that another important form of chromatin plasticity is the replacement of histone subunits within existing nucleosomes with histone variants. Work concentrates on the histone variant H3.3, and associated changes in nucleosomal turnover, in animal depression models and postmortem tissue from depressed humans.
- Project 4 (PI, Carol Tamminga, UT Southwestern; Schahram Akbarian, Mount Sinai) Working with Projects 1 through 3, Project 4 investigators validate numerous findings from mouse models in human depression, which ensures that the other Projects remain focused on mechanisms relevant to the human syndrome. As in the other Projects, attention to sex differences is a major theme. In parallel, Project 4 defines novel transcriptional and epigenetic abnormalities in the depressed human brain, findings which are then fedback to mouse models to understand the underlying mechanisms involved. Project 4 is thus essential for the bidirectional translation that is at the core of our Center.