The primary focus of the Epigenetic Etiology of Human Disease Laboratory of Keith D. Robertson, Ph.D., is to understand the role of DNA methylation and DNA hydroxymethylation in human health and disease.
Epigenetic modifications regulate accessibility and stability of the DNA and ultimately determine how, when and where genetic information will be used without altering its composition. Epigenetic marks within the human genome include those that target the DNA (methylation and hydroxymethylation) and those that target the histone proteins that package the DNA (methylation, acetylation and many others).
Regulated changes to DNA epigenetic marks are essential for normal human development. Unique epigenetic profiles impart stem cells with their ability to differentiate into any cell type, despite their DNA content being identical to specialized cell types throughout the body. In human diseases such as cancer, diabetes, cardiovascular disease and neurological disorders, epigenetic marks are subtly to profoundly altered. For example, disrupted DNA methylation patterns are a universal feature of all tumors; they occur early during development and actively contribute to cancer initiation and progression. In fact, many cancers may arise from stem cells that have sustained aberrant epigenetic changes due to harmful environmental exposures.
Drugs targeting aberrant epigenetic changes exist and many more are in development. These agents provide novel ways to target tumor cells or restore normal epigenetic states because epigenetic modifications, unlike genetic mutations, are reversible. Use of such drugs can be tailored to the patient's particular epigenetic and genetic landscape (individualized medicine).
In addition, detection of aberrant DNA methylation in bodily fluids holds great promise as a noninvasive early detection biomarker. This permits individuals at most risk to be identified and treatment initiated while the disease is in its earliest and most treatable stage.