We are in the midst of a revolution in the genomic sciences so profound and unprecedented that it will forever change the way we view biology and medicine, particularly with respect to the evolution of complex cognitive and behavioral functions, the mechanisms governing brain development and gene-environmental interactions, the etiology of neuropsychiatric diseases, the harnessing of endogenous neural stem cells to promote dynamic tissue remodeling in response to injury or disease and the development of new generations of more selective and efficacious pharmacoepigenomic therapeutic reagents. Epigenetics refers to a previously uncharted world of sophisticated molecular mechanisms required to orchestrate dynamic and continuous changes in the profiles of gene expression and the deployment of functional gene networks to promote synaptic and neural network plasticity, neuronal homeostasis and adaptive stress responses as well as multigenerational inheritance of complex behavioral traits, susceptibility to diverse neurological disease states and enduring responses to a spectrum of multifactorial environmental insults. The speakers will address all of these seminal issues. The first half of the meeting will focus on epigenetics and brain-behavior relationships. This will include an overview of the four cardinal mechanisms of epigenetic regulation of gene networks, cellular processes and neurobiological systems with an emphasis on the role of these mechanisms for promoting explosive innovations in human brain form and function in health and specific disease states. The role of various environmental and interoceptive stress responses and unique and plastic epigenetic adaptive responses to these conditions will next be explored. The influence of prenatal and perinatal care and individual differences in neuroendocrine functions for programming the epigenome for later nervous system functioning and adaptations will next be examined. Finally, the role of critical developmental periods for sculpting components of the evolving epigenome will be presented and its importance for determining the vulnerability of the nervous system to late-onset diseases will be outlined. The second half of the meeting will focus on epigenetics and neuropsychiatric diseases. The role of various components of the epigenetic tetrad of molecular mechanisms involved in an Xlinked form of genomic imprinting will be highlighted and reviewed with particular emphasis on the role of this allele-specific epigenetic """"""""tagging"""""""" mechanism for developmental as well as adult brain and behavioral functions. The importance of deregulation of components of the histone code and nucleosome and higher-order chromatin remodeling for the etiology of major depressive disorders will next be explored. Thereafter, the multifaceted clues that autism spectrum disorders represents a fundamental disorder of epigenetic mechanisms and associated deregulation of neural circuits mediating cell identity, neural network connectivity and social behaviors related to intragenomic conflicts between parental contributions to allelespecific expression and associated regional brain functions will be examined. Further, support for the role of alterations in DNA methylation, methyl CpG binding proteins and multifaceted components of the chromatin code in the etiology of schizophrenia will be outlined. Finally, the role of complex epigenetically-mediated alterations in RNA regulatory circuitry and in the tertiary structure of DNA: RNA intermediates associated with abnormal expansion of microsatellite repeats present in the trinucleotide repeat subset of neurodegenerative disorders will be discussed with regard to the emerging concept of RNA-dominant diseases associated with intricate and evolving disease phenotypes and novel modes of individual disease inheritance. All speakers will emphasize the importance of these novel and state-of-the-art concepts for the development of unique classes of pharmacoepigenomic designer therapeutic agents.
The goal of this meeting will be to provide a state of the art view of the emerging field of epigenetics and epigenomic medicine and its unique relationship to neural development, brain evolution, gene-environmental interactions during developmental as well as adult critical periods, learning and memory, neural stem cell biology, the pathogenesis of neurodevelopmental, neurodegenerative and neuropsychiatric diseases and the development of new classes of more selective and efficacious pharmacoepigenomic therapeutic reagents. Attendees will gain an understanding of the importance of incorporating these novel concepts and biological frameworks for enhancing clinical care, fostering clinical and translational research, developing novel early disease biomarkers and integrative epigenomics profiling for disease risk assessment, early diagnosis and as objective measures of therapeutic efficacy and for contributing to improving the bench-to-bedside interface in the clinical neurosciences. Through publication of the proceedings information critical to future research and clinical care to a wider audience will be provided.
