STORIES: Neuro-Epigenetics
Researchers: Andrew Feinberg, James Potash, Sarven Sabunciyan, Robert Yolken

Epigenetics, the study of heredity not coded in DNA sequences, is at the center of modern medicine because it can help to explain the relationship between an individual’s genetic background, the environment, aging, and disease. It can do so because the epigenetic state varies among tissues and over the course of a lifetime, whereas the DNA sequence remains essentially the same.

As cells adapt to a changing internal and external environment, epigenetic mechanisms can “remember” these changes in the normal programming and reprogramming of gene activity. The role of epigenetic changes in cancer is well established, and enormous excitement has grown over its potential role in brain development and function and neuro-psychiatric disease.

In the past year a major focus of the Neuro-Epigenetics core has been to develop a high throughput platform for analysis of DNA methylation across the human genome. Termed CHARM, for “Comprehensive High-Throughput Arrays for Relative Methylation,” this microarray-based method is agnostic to preconceptions about the location of DNA methylation. It allows interrogation of 4 million sites of DNA methylation per sample simultaneously. A key to the success of CHARM is a new mathematical approach which can extract quantitative methylation data regardless of the underlying DNA sequence.

The Neuro-Epigentics core is already discovering remarkable information. Over the next several years this initiative will offer an array of services to assist JHU brain researchers. It will also generate critical genome-wide methylation data in a variety of cortical and subcortical areas as well as the cerebellum, hypothalamus, midbrain, pons and the medulla oblongata. These targets will enable researchers to broadly sample across major brain regions while focusing on areas critical to neuropsychiatric diseases. This work will be completed in humans, mice, rats and rhesus macaques.

There have been impressive early returns on the investment in neuro-epigenetics. To help set priorities for the use of the neuro-epigenetics resources, the BSi Scientific Review Panel will review proposals and provide pilot grant support. Additionally, The School of Medicine is devoting new space for this work in the Institute for Basic Biological Sciences (IBBS). The Neuro-Epigentics core is also home to the first course in Epigenetics at Hopkins.

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