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Overview

Rothbart Laboratory

General Lab Overview

Think of epigenetics as a set of control switches that operate in every cell in the body. These switches help pack and unpack DNA, the spiraling molecule that acts as the blueprint for life.

In order for DNA to fit into the cell, it must be tightly balled up much like a crumpled piece of paper. For the information contained within the genetic blueprint to be read, however, it must be unfolded.  Epigenetic mechanisms help open up the DNA, allowing access to the packaged blueprints contained within.

Epigenetic mechanisms determine the identify and function of each cell during development; some become  heart cells, some become brain cells, and so on. Epigenetics help keep these cell types in their determined states.

In recent years, it’s become clear that when epigenetic control switches go awry, it can lead to diseases such as cancer, Parkinsons and others.

The goal of the work we do in the Rothbart Lab is to understand, at the basic mechanistic level, how these epigenetic control switches work so we can harness them to better treat disease.

Chromatin and Epigenetic Regulation

While all cells in the human body share a virtually identical genome, layers of regulation outside the genetic information encoded in the DNA (called epigenetics) program cells and give them unique identity. A complete copy of the human genome is tightly packaged inside every cell nucleus by wrapping around histone proteins.

This high level of DNA compaction presents a potential problem, as the underlying sequence must remain accessible to the vast protein machineries that utilize it for critical biological functions such as DNA replication, transcription and repair—all of which must occur at the appropriate place and time to promote cell growth, differentiation and proper organismal development.

The Rothbart Laboratory leverages in vitro and cellular biochemistry, computational and molecular biophysics, pharmacology, genomics and proteomics to uncover basic molecular and cellular mechanisms controlling chromatin accessibility, interaction and function. We are particularly interested in understanding how histone post-translational modifications and DNA methylation work together as a language or “code” that is read and interpreted by specialized proteins to orchestrate the dynamic functions associated with chromatin.

Importantly, large-scale genomic and epigenomic sequencing efforts, spearheaded in part by laboratories in VARI’s Center for Epigenetics, are revealing that deregulation of the cellular machineries responsible for regulating chromatin function contribute to the initiation and progression of multiple human diseases, including cancer. Unlike genetic abnormalities, DNA and histone modifications are reversible, making the writers, erasers and readers of these marks attractive targets for therapeutic intervention. Given this, our long-term goal is to translate the basic research performed in the lab toward novel chromatin and epigenetic target identification and drug discovery.