The Haghighi laboratory of neuroepigenetics is located jointly at the James J. Peters Veterans Affairs Medical Center and the Icahn School of Medicine at Mount Sinai. The research focuses on understanding the epigenetic basis of neurodevelopmental disorders.
Epigenetics refers to the functionally relevant modifications to the genome that do not involve a change in the DNA sequence. The human body contains a multitude of different cell types, the vast majority of which have identical genetic material, but perform very different functions. This diversity is generated through divergent gene regulation by epigenetic modifications of the genome. Cell types differ because they express different subsets of their full complement of genes. The epigenetic make-up of cells are not static, rather they undergo dynamic changes throughout an organisms’ development and environmental perturbations.
We investigate epigenetic changes in disease and normal human postmortem brain samples, providing a snapshot of potential epigenetic abnormalities associated with disease neuropathology. Epigenetic modifications throughout brain development are also crucially important in diseases with neurodevelopmental origins. Defining possible pathological epigenetic factors associated with neurodevelopmental diseases require knowledge of the epigenetic modifications that occur during normal brain development. Therefore, we are interested in how epigenetic modifications are involved in normal brain development, and are characterizing epigenetic signatures that define neurodevelopmental trajectories in humans and rhesus monkeys. This makes possible the identification of primate-common and species-specific epigenetic marks involved in neurodevelopment. This comparative approach is essential for developing monkey models of normal and pathological brain development, but also may lead to the delineation of epigenomic changes that are specific to humans and underlie human-specific features of normal development and vulnerability to neurodevelopmental disorders. This new knowledge will provide a fresh and expanded view into neuronal development as well as higher cognitive function and dysfunction.
- Large-scale DNA methylation profiling of depression and schizophrenia in prefrontal cortical neurons
- Candidate gene analysis of DNA methylation abnormalities associated with depression and suicide
- Neuronal DNA methylation profiling in primate neurodevelopment
- Development of algorithms for detection and quantification of allele-specific methylation.