TAMEST Profile: Joshua T. Mendell, M.D., Ph.D., UT Southwestern Medical Center

Dr. Joshua T. Mendell, UT Southwestern Medical Center, knew from an early age that he wanted to pursue a career in research. The son of a physician–scientist, he began working in a molecular biology laboratory when he was just a teenager and continued to perform laboratory research as an undergraduate at Cornell University.

Dr. Mendell pursued a Ph.D. and M.D. at Johns Hopkins University and received the degrees in 2001 and 2003, respectively. He remained at Johns Hopkins as a faculty member before moving to UT Southwestern Medical Center in 2011. He says he discovered his passion for molecular biology research due to the potential of this field to solve major unresolved questions in biology and medicine.

In 2016, Dr. Mendell was recognized by TAMEST with the Edith and Peter O’Donnell Award in Medicine for his pioneering work on the functions of noncoding RNAs in cancer and tissue regeneration. His work continues to examine the regulation and function of different classes of noncoding RNAs, with particular emphasis on the roles of these molecules in normal physiology and in diseases such as cancer.

Also a former TAMEST Protégé, Dr. Mendell says he has tremendous admiration for TAMEST and its efforts to mobilize the greater Texas research community. This past year, he served as the Medicine Co-Chair for the TAMEST 2023 Annual Conference, Forward Texas – Accelerating Change, in Houston, Texas.

TAMEST connected with Dr. Mendell to hear more about his research and why it is so important to support the next generation of research leaders.

Please tell us a little about yourself and your work. 

Growing up in Columbus, Ohio, I was first introduced to the world of scientific research through my father, who is a physician scientist. In high school, I had an opportunity to participate in a National Science Foundation program that enabled students to perform research in laboratories at The Ohio State University. These experiences sparked my interest in science and medicine at an early age. I then went on to Cornell University where I studied genetics and then later completed M.D. and Ph.D. degrees at Johns Hopkins University.

Fast forward to 2023, I now lead a laboratory in the Department of Molecular Biology at UT Southwestern composed of a group of scientists who share a passion for “RNA biology,” a field that focuses on the various functions performed by RNA in cells and the mechanisms through which genes are regulated at the RNA level.

As the recent COVID-19 pandemic has illustrated, RNA has the power to dramatically reprogram cells, leading to both pathologic effects, as exemplified by infection with RNA-based coronaviruses, or beneficial effects, such as priming of the immune system after administration of an mRNA vaccine. In our laboratory, we study how cells use RNA molecules to control the expression and activity of proteins, how these processes go awry in diseases such as cancer, and how we can take advantage of this knowledge to develop new therapies.

How did you first discover your research field/path?

I was first was introduced to the field of RNA biology as a graduate student. In our current age of mRNA vaccines and RNA viruses, RNA biology is at the forefront of biomedical research. But when I started working in this area in the 1990’s, many fundamental questions remained to be investigated. Given the central role of RNA in gene expression and regulation, and the potential for discoveries in this area to translate into new therapeutic approaches for various diseases, I was extremely excited to delve deeply into this field.

Upon completion of my dual M.D.-Ph.D. degree, my career faced a crossroads. Typically, at this stage, graduates go on to residency programs for additional clinical training prior to becoming practicing physicians. I, on the other hand, was offered a unique opportunity to join the faculty at Johns Hopkins and build a research laboratory focused on RNA biology.

I jumped at this chance to focus 100% of my time on research and I have never looked back. After seven years on the faculty at Hopkins, I was recruited to the Department of Molecular Biology at UT Southwestern in 2011 to continue my work on RNA in Dallas. I made this move because I was convinced that the infrastructure and colleagues at UT Southwestern would further empower our research. Over a decade later, I continue to feel very fortunate to be able to explore the fascinating world of RNA biology at this world-class institution.

What makes you most passionate about your work?

What initially drew me to the study of RNA biology were the fascinating and important questions remaining to be answered in this field. For example, the mechanisms through which genes are regulated are fundamental for understanding development, physiology, and disease.

However, most work on gene regulation has focused on the regulation of transcription, the initial production of the messenger RNA. Nevertheless, after transcription, many additional steps control how much protein is ultimately made from a gene. For example, the mRNA has to be spliced, exported to the cytoplasm, translated into protein, and eventually degraded. Each of these steps in gene expression are tightly regulated and each step can go awry in disease. Discovering new fundamental mechanisms of gene regulation that function at the RNA level is extremely exciting and important.

Beyond regulation of mRNAs that encode proteins, another fascinating aspect of RNA biology that we study are so-called “noncoding RNAs.” These are RNAs produced by cells that do not encode proteins, but rather perform novel functions directly at the RNA level. For example, we have extensively investigated the functions of a class of noncoding RNAs called “microRNAs,” which, as the name implies, are among the smallest RNAs produced by cells. microRNAs directly control the translation and stability of protein-coding mRNAs and, as a result, play key roles as regulators of gene expression in normal physiology and in diseases. Our laboratory has shown that microRNAs are important drivers of cancer and can be targeted to suppress tumor development.

We also study other classes of noncoding RNAs, including “long noncoding RNAs,” which can participate in many aspects of cell biology. For example, we discovered a long noncoding RNA that prevents premature aging in mice by ensuring the accurate transmission of chromosomes during cell division. These classes of noncoding RNAs represent just one part of the exciting universe of noncoding RNAs that our laboratory is exploring.

You were awarded the 2016 Edith and Peter O’Donnell Award in Medicine for your pioneering work on the functions of noncoding RNAs in cancer and tissue regeneration. What was that experience like for you? 

I was deeply honored to receive the O’Donnell Award and I greatly appreciate being nominated for this award by the Chair of my department and TAMEST Member Eric N. Olson, Ph.D. (NAM, NAS). It is truly inspiring for a young scientist to be recognized by the illustrious members of TAMEST and it motivated me to keep taking risks in order to push our science forward into uncharted territory.

It was also wonderful to share this honor with my laboratory members, whose hard work made it possible, my colleagues at UT Southwestern, whose collaboration elevated our science, and my family, whose unconditional support and love enabled me to pursue this career that I love.

Seven years after receiving the award, you signed up to co-chair the TAMEST 2023 Annual Conference in Houston, Texas. What made you decide to volunteer your time and expertise to help shape this year’s conference?

I was honored to contribute to TAMEST as a co-chair of the Annual Conference. The incredible accomplishments of all the TAMEST members are an inspiration to all scientists in Texas.

The annual meetings provide a great venue to bring together a highly diverse group of physicians, scientists, and engineers who do not often have an opportunity to interact, thereby offering unique learning and collaborative opportunities. The fantastic staff at TAMEST made our job as organizers very easy and they deserve most of the credit.

Additionally, you and your conference co-chairs served as judges for the TAMEST 2023 Protégé Poster Challenge. How was this poster challenge different from others you may have seen at other conferences?

Most conferences that I attend are much more narrowly focused on my field of research. The poster challenge at the TAMEST Annual Conference is fundamentally different, covering a wide range of topics.

As such, it provided a wonderful opportunity to learn about research projects that are well outside my area of expertise.

What was the hardest part about judging the protégé posters? The best?

The hardest part and the best part of judging the posters was the same: the incredible quality of the research made it nearly impossible to pick out a small number of finalists. All of the judges agreed that we could have easily chosen many others to be featured in the final group of three posters chosen for oral presentations.

Why is highlighting up-and-coming researchers in Texas important?

TAMEST members represent the most accomplished scientists in the state of Texas. It is inspiring for young researchers to be highlighted and celebrated by this group.

As a young researcher, it is challenging to do something truly unique and important, and doing so requires taking risks. It is highly motivating for young researchers to see what the most successful researchers in Texas have accomplished and continue to accomplish in their careers.

Is there anything else you’d like to add?

I would just like to thank TAMEST for supporting and inspiring me through the O’Donnell Award and as a protégé at past meetings.

I am very happy that I was able to give back a small amount to TAMEST by co-organizing the Annual Meeting this year. I deeply appreciate being featured in this profile.

Photos and slides from the TAMEST 2023 Annual Conference are available at TAMEST.org/2023.

Dr. Mendell is a Professor of the Department of Molecular Biology and the Charles Cameron Sprague, M.D. Chair in Medical Science at UT Southwestern Medical Center. He is also an Investigator of the Howard Hughes Medical Institute.