Project Name: The Functional Role of Chromatin Marks for Enhancer Fidelity and Integrity


Over the past 10 years, new technology has made it possible to complete detailed profiling of genetic mutations and the genome structure in both normal and cancerous cells. (The genome is the complete set of genes or genetic material present in a cell.) In particular, we have been able to broadly map regions of the genome that are open (turned on), enabling expression of genes from the underlying DNA sequence, or closed (turned off). The epigenome (which is a multitude of chemical marks that tell the genome what to do) controls which regions of the genome will be open or closed. The epigenome provides fine-tuned regulation of gene expression patterns through the addition of chemical modifications to the physical genome.


Importantly and unlike genetic abnormalities, epigenetic modifications are reversible, therefore focusing on the epigenome is a promising therapeutic avenue for cancer treatment and prevention. In addition to the genes themselves, we now appreciate that enhancers (i.e., regions of the genome that are distant in linear space from functional gene units) are necessary for proper gene expression and are also epigenetically regulated. Proper control of enhancers is necessary for development, cellular identity, and prevention of disease states. However, epigenetic mechanisms of enhancer control are poorly understood. My current research is therefore aimed at understanding the role of the epigenome in the control of enhancers.


Prostate cancer in particular is susceptible to changes in the epigenomes of enhancers. My studies will use a recently developed model system of prostate cancer progression to characterize the dynamics of epigenome reprogramming in this disease. The results of this work will help identify epigenetic mechanisms that contribute to prostate cancer and will suggest new avenues of pursuit for therapeutic interventions to correct aberrant gene regulation in this disease. Since mechanisms regulating the genome being open or closed are often the same across tissues, the conclusions drawn from my studies will likely extend across various cancer subtypes.


Summer 2018 Update from Dr. Tiedemann: I am currently a postdoctoral researcher at the Van Andel Research Institute in Grand Rapids, MI, and I am entering my second year of funding by the American Cancer Society - Michigan Cancer Research Fund. To date, I have made significant progress on a project that aims to dissect how packaging of our DNA changes in cancer. One of my colleagues recently identified a unique pattern in DNA structure that occurs during aging and cancer progression. Our work has uncovered a protein that we believe plays a major role in conferring this unique signature, and we are currently preparing a manuscript to share our results. Our future work will focus on uncovering how this unique signature contributes to changes in DNA function in cancer and how our protein controls this process.