TAMEST Member Profile: Sharon Y.R. Dent, Ph.D. (NAS), MD Anderson Cancer Center

Dr. Sharon Y.R. Dent is Professor Emeritus of Epigenetics and Molecular Carcinogenesis at The University of Texas MD Anderson Cancer Center. She is a global leader in chromatin research and her foundational work has helped define the role of chromatin in both normal developmental processes and disease states.

In May, she was elected to the National Academy of Sciences (NAS) for her work in the field of epigenetics, which studies how changes in genome folding impacts gene expression programs that control cellular identity and behaviors without changing the DNA sequence.

Her research helps scientists and clinicians develop therapeutic strategies to target processes that can impact cancer development and progression. Most recently, her work showed that the SAGA complex interacts with specific oncoproteins, MYC and MAF, which promote the transformation of normal cells into tumors by dysregulating the signaling pathways involved in cell growth.

Prior to her election to the NAS, Dr. Dent attended several TAMEST Annual Conferences as a TAMEST Protégé. She says the experience enabled her to meet and interact with National Academy members across the state and learn more about the interdisciplinary research happening in Texas.

TAMEST connected with Dr. Dent to learn more about her long and successful commitment to education, research and mentoring.

Tell us about your pathway to cancer research, particularly the field of epigenetics.

I went to college thinking I would be a science teacher, because I had fantastic biology, chemistry and math teachers in high school. That changed when I had the chance to work in a research lab as a ‘work study’ student as an undergraduate at North Texas State University (now University of North Texas). I simply fell in love with research.

My advisor, Dr. Myron (Mike) Jacobson, then encouraged me to go to grad school, and I was thrilled when I was accepted into the Biochemistry program at Rice University. There I had a chance to work with a young professor, Dr. Susan Berget, who played a prime role in the discovery of RNA splicing during her post doc with Dr. Phil Sharp.

That was the beginning of my interest in gene regulation, which led to an interest in understanding how the organization of DNA into chromatin influenced gene expression. I was introduced to Dr. C. David Allis, then a new Assistant Professor at Baylor College of Medicine, during my time in Sue’s lab at Rice. Dave had already established a reputation in the chromatin field, discovering new variants and post-translational modifications of histones.

His love of science was contagious, and his use of a unique model organism, Tetrahymena, was intriguing. I was again thrilled when Dave accepted me as a post-doctoral fellow, and working with him was a life/career changing move. I knew I wanted to focus on chromatin, but I also realized that I wanted to learn more genetics, so I continued my training as a Senior Staff fellow at the NIH with Dr. Robert Simpson. There I used yeast genetics to define how chromatin contributes to cell type specific gene expression or repression.

What about genetics interested you to continue?

Specifically, I found that a corepressor complex induced a highly organized chromatin state to turn genes off. I carried that project with me when I started my own lab at MD Anderson, and we generated some of the first direct demonstrations that corepressors interact directly with specific histones and with specific histone modifying enzymes.

We also renewed collaboration with Dr. Allis and were part of the team that identified the first transcription related histone acetyltransferase. These discoveries laid the groundwork for the three decades of research in my lab. My colleagues at MD Anderson helped me and my lab group expand our studies into mammalian systems, especially genetically engineered mice, and later, cancer cells.

You are a global leader in chromatin research and your research has helped define the role of chromatin in cancer growth and development. Explain why it is important to examine how certain mutations lead to abnormal chromatin folding and subsequent diseases, such as cancer.

Fundamentally, cancer occurs when a cell ‘forgets’ what it is supposed to be and do, taking on a new identity along with harmful growth and/or invasive characteristics. Mutations in the DNA, especially in genes encoding transcription factors that act as tumor suppressors, such as p53, underlie many of these changes in cell behavior.

Epigenetic changes, including changes in DNA methylation or chromatin folding, also impact gene expression programs that influence cell identity, growth and behavior. Unlike genetic mutations, though, epigenetic changes are often reversible.

Understanding how chromatin organization and DNA methylation patterns are regulated in normal cells is critical to understanding how these processes go wrong in cancer. We can then begin to understand how to possibly reverse those changes to either change cell behavior or encourage tumor cells to die.

What makes you most passionate about your work? 

Two things. First, the thrill of making a discovery is hard to match. I love mysteries, and building and testing hypotheses is a fun way to work towards solving a biological mystery.

I have to say, though, that some of our biggest discoveries came from unexpected results, and that is even more exciting, because the new, unexpected finding changes not only your thinking, but thinking in the field.

Second, I love working with students and post-docs and making discoveries together. I find it energizing, and I always learn as much or more from them as they do from me.

You were elected to the National Academy of Sciences in 2024 and became a member of TAMEST. What does being a member of NAS and TAMEST mean to you? 

Of course, it is an amazing honor to recognized by your peers and being elected to the NAS and to TAMEST honors everyone who ever held a pipette in my lab and every discovery we made together. 

Before becoming a member of TAMEST, you attended several conferences as a TAMEST protégé. Talk about your experience with the TAMEST Protégé Program.

Attending the TAMEST conference as a protégé was quite an honor. It gave me an opportunity to hear from and interact with NAS members from across the state. I also learned a lot from the cross-disciplinary nature of the conference. 

Now that you are a member, do you plan to nominate a protégé to join you at the TAMEST 2025 Annual Conference and why? 

Yes.  We have a such rich talent pool in Texas. I want to support our junior scientists to help enable them to reach their full potential, as others did for me.

Why do you live and work in Texas? 

I am a native Texan, but that is only part of the answer. Mostly it is due to the breadth and depth of science available here as well as the highly collegial nature of research in Texas.

Is there anything else you’d like to add?

I am honored to be inducted into TAMEST, and I hope that I can ‘pay forward’ some of the great opportunities afforded to me through service in TAMEST and in the NAS.