Recent research has suggested that we are not simply the outcome of our DNA blueprint, but that we also have an epigenome that sits on top of our DNA and ultimately dictates which of our genes are expressed. In this way, DNA is not our destiny. Rather, the relationship between our DNA, the environment we live in, and our lifestyle choices become intertwined. Dr. John Denu, Professor of Biomolecular Chemistry at the University of Wisconsin, studies the underlying mechanisms of how lifestyle and diet controls our epigenome and how that knowledge can be used to make decisions to improve our lives. Specifically, he and his team are exploring how diet, metabolism, and our gut microbiome influence our epigenome to affect diabetes, cancer, and neurological disorders. In so doing, Dr. Denu hopes to learn how to change the epigenome in order to combat disease and aging.

For the last twenty years, Dr. Denu and his team of Ph.D. students and postdocs have successfully been making novel connections between biological processes that have not been discovered. Additionally, rather than simply focusing on correlation, his research takes a bench-to-bedside approach by probing the true mechanistic underpinnings of aging and disease to then make discoveries about how to impact the lives of patients. Therefore, Dr. Denu and his team’s results could have a profound affect on the way we choose to live our lives and the medicines that could rebalance gene expression through epigenetic pathways. Strengthened by collaborations with about seven research groups throughout the world, Dr. Denu’s research provides unique expertise to accelerate discovery by making breakthroughs that extend our healthspan.

Current research includes:

• Molecular Basis of Caloric Restriction (CR): CR is defined by a reduction in calories, without loss of nutrition. In almost every animal that has been studied, from yeast to humans, CR has resulted in the extension of lifespan and increases in healthspan. Dr. Denu wants to understand the biological mechanisms responsible for changing the epigenome and thus extending lifespan and healthspan. Contrary to advocating for a CR diet, Dr. Denu hopes to use his findings to develop nutraceuticals, medicines, or lifestyle regimens that could mimic the effect of CR.

• Gut Bacteria: How do gut bacteria influence your liver tissue or brain in your epigenome? Dr. Denu is on the forefront of making sense of the interaction between microbiota and the epigenome. He and his team hope to understand how probiotics, like those found in yogurt, influence health.

• Folic Acid Supplementation: Folic acid supplementation has been found to successfully increase the health of expectant mothers’ pregnancies. Through a collaboration with a neurosurgeon at UW-Madison, Dr. Denu is studying how folic acid affects the epigenome. Preliminary research has led to profound discoveries that are helping to get to the bottom of how epigenetics affects long-term gene expression.

• Tool Development: While the discoveries made in Dr. Denu’s lab are of paramount importance for the health of our aging population, the tools and methodologies he has created for the epigenome are an important contribution to science as well. He and his team have continued to develop technology, in terms of diagnostic tools that monitor the epigenome, so that other scientists can also track real chemical changes in many human disease states.