In its simplest terms, epigenetics is the study of the biological mechanisms – particularly those that control DNA packaging – that switch genes on and off. These mechanisms generally include tags or marks to DNA and proteins that change gene expression but not the actual sequence of DNA. By analogy, it is like a uniform and equipment for an athlete that impacts how well he or she performs but does not change who they are.
Comprehensive Cancer Center investigators are developing sophisticated technologies and chemistry methods to detect different kinds of epigenetic marks and understanding how they impact gene and cellular function. Importantly, our scientists are discovering how changes in the patterns of marks (like brand new uniforms or equipment) are involved in cancer and may be targeted for cancer therapy.
Chuan He, PhD, is developing new sensitive and robust methods for detecting epigenetic marks on DNA. His research has shown that RNA modifications, such as messenger RNA methylation, can be heritable, dynamic, and are different in healthy and disease cells.
Alex Ruthenburg, PhD, is developing new methods for more accurately analyzing DNA-protein interactions. One of the most widely used tools is chromatin immunoprecipitation (ChIP), a technique that allows researchers to examine interactions between specific proteins and genomic regions. However, ChIP is a relative measurement, and has significant limitations that can lead to errors, poor reproducibility and an inability to be compared between experiments. Ruthenburg and his colleagues developed a new and more accurate technique called Internal Standard Calibrated ChIP (ICeChIP).
Research by Yingming Zhao, PhD, and colleagues has provided important clues to how metabolism controls gene expression. Key to their discovery was identification of a new type of post-translational modification on histone proteins called lysine ß-hydroxybutyrylation (abbreviated Kbhb). Post-translational modifications are chemical marks added onto proteins and are known to have profound effects on protein function.
Nucleic acids, which include DNA and RNA, carry the genetic information that encodes the building blocks of cells and tissues. Chuan He, PhD, and colleagues study how modifications, such as methylation, to RNA can lead to changes in how genes are expressed and, ultimately, result in disease. This field is referred to as epitranscriptomics. He’s laboratory discovered the first RNA demethylase, an enzyme that removes methylation modifications, and showed for the first time that it is possible to reverse RNA modifications.
He will lead Chicago’s first Center of Excellence in Genomic Science—one of only seven such centers in the United States. The Center will create new technologies for studying how RNA is regulated by chemical modifications inside cells.
In 2015, He and colleagues identified and characterized the function of the N6-methyladenine (6mA) DNA mark in Chlamydomonas, a green algae of potential use in biofuel production.
Lucy Godley, MD, PhD, is working to understand the impact of epigenome (epigenetic modifications across the entire genome) and specific modifications on blood cell development and hematological malignancies.
Our investigators are conducting the latest clinical trials with drugs that target epigenetic pathways. For example, a team led by Olatoyosi Odenike, MD, and Wendy Stock, MD, recently conducted a phase I study of the histone deacetylase inhibitor belinostat and DNA methylation inhibitor azacytidine in advanced myeloid neoplasia.