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.
Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression.
Haghighi Fatemeh, Ge Yongchao, Chen Sean, Xin Yurong, Umali Michelle U., De Gasperi Rita, Gama Sosa Miguel A., Ahlers Stephen T., and Elder Gregory A. Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury. Journal of Neurotrauma. July 2015, 32(16): 1200-1209. doi:10.1089/neu.2014.3640.
Milekic M, Xin Y, O’Donnell A, Kumar K, Bradley-Moore M, Malaspina D, Paul S, Moore H, Ge Y, Edwards J, Haghighi F, and Gingrich J. (2014). Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal behavior and dysregulated gene expression. Molecular Psychiatry [Epub ahead of print]. PMID: 25092244
Haghighi F, Xin Y, Chanrion B, O’Donnell AH, Ge Y, Dwork AJ, Arango V, and Mann JJ. (2014). Increased DNA Methylation in the Suicide Brain. Dialogues Clin Neurosci, 16(3):430-8. PMID: 25364291
Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, and Ecker JR. (2013). Global epigenomic reconfiguration during mammalian brain development. Science, 341(6146), 1237905. PMID: 23828890
Deo AJ, Huang YY, Hodgkinson CA, Xin Y, Oquendo MA, Dwork AJ, Arango V, Brent DA, Goldman D, Mann JJ, and Haghighi F. (2013). A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction. Psychiatr Genet, 23(2), 47-55. PMID: 23277131
Xin Y, Chanrion B, O’Donnell AH, Milekic M, Costa R, Ge Y, and Haghighi FG. (2012). MethylomeDB: a database of DNA methylation profiles of the brain. Nucleic Acids Res, 40(Database issue): D1245-9. PMID: 22140101
Xin Y, O’Donnell AH, Ge Y, Chanrion B, Milekic M, Rosoklija G, Stankov A, Arango V, Dwork AJ, Mann JJ, Gingrich J, Haghighi F. (2011). Role of CpG Context and Content in Evolutionary Signatures of Brain DNA Methylation. Epigenetics, 6(11), 1308-18. PMID: 22048252
Xin Y, Ge Y, Haghighi FG. (2011). Methyl-Analyzer—whole genome DNA methylation profiling. Journal of Bioinformatics, 27(16), 2296-7. PMID:21685051
Xin Y, Chanrion B, Liu M, Galfalvy H, Costa R, Ilievski B, Rosoklija G, Arango V, Dwork A, Mann JJ, TyckoB, Haghighi F. Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices. PLoS One. 5(6), e11357. PMID: 20596539
Meet the Team
Post-doctoral Research Associate
Job opportunities are available in the Laboratory of Medical Epigenetics. Internationally regarded for its dedication to medical science, Mount Sinai is home to an array of leading research institutes, centers, and laboratories, all of which work toward rapidly translating advances in basic science into innovative patient care. Mount Sinai’s Fishberg Department of Neuroscience, a major component of Mount Sinai’s Friedman Brain Institute, sponsors innovative research in basic and translational neuroscience at the molecular, cellular, systems, and behavioral levels. The Haghighi laboratory is studying the epigenetic profiles of human brain development and its emerging role in gene regulation, as well as its fundamental importance for our understanding of normal and pathological neuronal function. Epigenetic patterns in the genome vary among tissues and cell types in normal and pathological states.
A major unanswered question is how epigenetics plays a role in neuronal development and how alterations in normal epigenetic processes during development lead to neurodevelopmental diseases such as autism and schizophrenia. Next-gen sequencing technologies now allow a global view of whole genome epigenetic profiles. Studies involve statistical and bioinformatic analyses of data from whole genome DNA and histone methylation profiling via BS-seq and ChIP-seq to detect differentially methylated regions associated with disease and their potential function through genomic data mining. This interdisciplinary group offers an excellent environment to uncover new fundamental principles and regulatory mechanisms in this emerging area of neural-epigenetics.