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Exploring the Functionality of Nuclear Receptors with Dr. Burris

By Patrick Sherry

Thomas P. Burris, Ph.D., Director of the University of Florida Genetics Institute and Chair of the Department of Pharmacodynamics designs small molecules that can modulate the activity of nuclear receptors to be used as therapeutic agents for various diseases. Through the discovery or creation of novel compounds, he hopes to improve human health by utilizing chemistry and genetics.

Dr. Burris primarily researches nuclear receptors, which regulate gene expression directly as transcription factors. There are 48 nuclear receptors within the human body; however, scientists do not know the natural ligands for about 24 of them. Due to this, identifying ligands that regulate their activity can assist in finding treatments for a variety of bodily functions. The Burris Lab’s mission is to discover how the remaining receptors function and develop compounds to influence health outcomes.

“Almost every receptor that we know how to target in the nuclear receptor superfamily, we’ve been able to design drugs that reach the clinic and have a beneficial impact on human health,” said Burris. “The remaining 24 that we haven’t designed drugs for yet and we are in the process of [doing so] – there’s still a rich area for figuring out how to improve health.”

This research into nuclear receptors has extensive applicability in health and wellness, but Dr. Burris initially was not keen on pursuing a research-based career. Originally, he wanted to become a physician because he was unaware that a scientific research career was an option. However, after completing an undergraduate degree in chemistry, he was admitted into a graduate program in biophysics. These two degrees gave him key training in both areas, which assisted him in pursuing drug discovery.

“When I started taking high school chemistry – understanding how chemistry is such a critical, basic science for understanding how biological processes work, that’s where everything clicked,” said Burris. “When I went to college and realized that basic research was a career route, I started shifting directions.”

While working on his Ph.D. in neuro-endocrinology –focusing on how hormone secretion was regulated, his interesthis interest expanded into the genetic and biological aspects that influence these processes. He learned about nuclear receptors through this academic pursuit as well. Overall, this experience kickstarted his future endeavors in nuclear receptor investigation that continues to this day. He further emphasized these interests by completing a postdoc with Dr. Bert O’Malley at Baylor College, who helped discover several nuclear receptors in the 1960s.

Subsequently, Dr. Burris spent 10 years in the pharmaceutical industry at Johnson and Johnson and Eli Lilly & Company, refining his skills and interest in drug discovery, chemical biology, and chemical genomics. He returned to academia in 2006, holding numerous high-profile positions at various institutions, eventually becoming the Director of the UFGI in 2021. All these achievements also do not include his entrepreneurial endeavors because he is also the co-founder of two biotechnology companies that focus on developing drugs to treat diseases and side effects of aging. All these experiences make Dr. Burris not only an expert in the field but a well-versed researcher and businessman able to push the understanding of nuclear receptors further.

“[Nuclear receptors] are very useful for understanding how things work, but I was interested in doing something that could yield a product that could have a direct impact on people in the relatively short term,” said Burris. “I saw that this receptor class was a way to combine my interest in chemistry, drug discovery, gene expression, genetics, and endocrinology all into one.”

Animal models like mice are key to understanding these processes and are used to test small molecules that can influence receptors. Prior to entering clinical trials, this model system provides insight into the underlying functionality of these processes and gains initial data on the effectiveness of certain compounds. Prior to focusing on a particular nuclear receptor to target with small molecules, Dr. Burris utilizes data from mice that are genetically engineered to suppress or overexpress of the receptors. In doing so, researchers can understand what biological and pathological processes receptors regulate and then see which compounds can be used to address them.

Technologies like improved drug screening, computer simulations that can guide drug design, genomic technology, and advances in structural biology at a modular level all assist in the development of Dr. Burris’ research as well. Rapidly advancing technology is overall useful but it can provide additional barriers that researchers have to address. However, Dr. Burris maintains that technology provides more benefits and offers more potential than challenges.

“It is challenging to keep up with all of the new technologies in general,” said Burris. “Technology is moving at a very fast rate so the number of tools you have in the toolbox is increasing so much. Things are popping up so quickly – improvements, known technologies, and new types of technologies. It’s challenging, but it certainly is exciting.”

Despite Dr. Burris’ extensive experience within the field, numerous accolades, and continuous advances in technology, his research can be difficult at times. But through collaboration and tenacity, he has been able to create a well-accomplished career in academia and business and also benefit human health and science in the process.

“It’s a puzzle,” said Burris. “I think what also excites me about this area is not just figuring out how the processes work, but we can actually design new things that then modulate those pathways. It is certainly exciting to be the first one to develop drugs that can regulate pathway receptors that have never been done before. These are tools that never existed before that could be translated potentially into being used by people to improve human health.”

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