New Faculty Spotlight: Understanding Epigenetics and Disease

Since his time as an undergraduate student, Patrick Grant, Ph.D., has always had an interest in cancer biology and the immune system. Now, as an associate professor in the Charles E. Schmidt College of Medicine, he researches epigenetic changes — and their role in diseases, such as cancer.

Grant grew up in the countryside of Suffolk, England, and attended the University of Portsmouth, where he earned a bachelor’s degree in biology and parasitology. Then, he earned a doctorate in medicine at Karolinska Institute in Sweden, focusing on immunology. “This proved to be a deeply enriching experience scientifically, culturally and personally,” Grant said.

Next, Grant attended Pennsylvania State University to work with Jerry Workman, Ph.D, just as the field of epigenetics was taking off. After four years, he was invited to join the University of Virginia School of Medicine in Charlottesville as a professor of biochemistry. The decision to go was a “no brainer,” he said, especially given the opportunity to work with C. David Allis, Ph.D., “a trailblazer in epigenetics.”

After spending the next two decades as a professor at UVA, Grant said he was ready for a new opportunity. That opportunity landed him at Florida Atlantic University (FAU). “Much of the attraction in joining FAU is their advancement of research pillars that focus on institutional strengths and the College of Medicine’s investment in directed research in the areas of genomics, precision medicine, and neuroscience, as well as their expert faculty devoted to biomedical research and education,” he said.

Here’s a look at Grant’s research and his advice for students:

What is your current research focus?

I currently have research that examines histone proteins, which pack and condense very long DNA molecules to fit into the cell nucleus, and how chemical changes to these proteins can result in diseases, such as cancer.

My lab has had a long-standing interest in identifying the enzyme systems that govern such modifications of the histone proteins. Changes to these histones have implications for how cancer cells multiply and develop resistance to chemotherapy. We have made an exciting discovery of a critical, but overlooked enzyme that when overexpressed in glioma, bladder, stomach, lung and other cancers, correlates with dramatically reduced survival and disease-free progression in patients. Obviously finding drugs that target this “new” enzyme is of great interest for the development of novel cancer treatments.

We also discovered a previously unknown enzyme system that modifies histones, called SAGA, which stands for Spt-Ada-Gcn5-Acetyltransferase. We found that SAGA function is abnormal in patients with the neurodegenerative disease called spinocerebellar ataxia 7 (SCA7) — a tragic and ultimately fatal disease that causes blindness and progressive cell death in the cerebellum region of the brain. We are focusing on candidate interventions for SCA7, which is currently untreatable.

And lastly, together with collaborators, we are studying how epigenetic and gene expression changes influence cocaine and opioid addiction.

Why do you have an interest in this research?

When I entered the field of molecular epigenetics research it was an emerging area with much to be learned. At the time I began research in this field, we knew nothing about the identity of enzymes that chemically modify histones, although their existence was predicted for many years. I find it particularly interesting that histone modifications play a major role in processes, such as turning genes on or off, can be influenced by the environment, and are often subverted in diseases, such as cancer. There are continuously reports of fascinating links between epigenetic regulation and health and disease. While epigenetics is now a hot topic, I think that it is fair to say that there is still much to be learned.

Did any mentors or professors influence your career path and interests?

I can think of a number of teachers, faculty, and mentors who helped pique my interest. My undergraduate professor, Mike Carter, Ph.D., introduced me to the concept of oncogenes, which is when a gene can transform cells into tumor cells, as well as some other concepts. However, the influence and encouragement of Workman and Allis cannot be understated. Allis was my mentor and colleague at UVA, and Workman was my postdoc advisor at PSU.

What brought you from Sweden to the U.S.?

For my doctorate research, I researched the regulation of antibody gene activity and the signals that lead to the diversity of antibody production. However, it became increasingly apparent that there was something critical missing in my studies — an understanding of how gene activity is controlled by chromatin, which is a combination of DNA, histones and other proteins that make up our chromosomes. After graduating, I decided to look for a postdoc where I could combine my curiosity —and lack of knowledge — of chromatin and histone biology with my interest in the regulation of gene expression. After meeting with a number of scientists, I decided to work with Workman at PSU, fascinated by his pioneering studies. It was there that I learned to be a biochemist and was introduced feet first into the rapidly emerging field of “epigenetics” and chromatin modification. It was a truly exciting time in the field and a highly productive postdoc.

What do you hope to accomplish with your research?

The links between these histone modifications and disease have never been clearer. I’m using cutting-edge techniques to study how histone modifications contribute to other diseases, as well as the development of resistance to treatment, like chemotherapy. Understanding these processes opens doors into how new treatments may be discovered.

Do you have any advice for becoming a researcher in your field?

Students interested in this career should attend research talks, read scientific articles, and reach out to their advisor, faculty and researchers to see what opportunities are available. They should ask what the burning questions are and who is doing this work. Doing this can help a student narrow down candidate graduate schools or postdoc positions to apply to. For undergraduates, it’s also important to seek out volunteer research opportunities and summer internships to get some exposure to life in the lab.

Ultimately, the best advice I can give after this is to follow your research interests. It is often unpredictable what the outcome of biomedical research experiments will be. There are many trials and tribulations in following ideas that have never been tested and we all have had our fair share of failures in the laboratory. Therefore, it is important to be passionate and motivated about the research you want to pursue.

Provisional Patent

Grant recently filed a provisional patent application, Apparatus and Method for UV-C Sanitization of Contaminated Masks in a Household or Workplace Environment, an invention to quickly sanitize face masks that have been reused.

The tests indicate the device eliminates microorganisms on the masks in five minutes. For more information on the invention, click here.