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Baije Xu, Ph.D.

Basic Science Award, 2024

What stood out about your research experience at UT Southwestern, and how did it shape your career?

At UT Southwestern, my research experience has been transformative, deepening my understanding of the neural regulation of energy balance and contributing to the development of potential treatments for obesity and other metabolic disorders. One of the most impactful aspects has been my work with genetically engineered mouse models, which allowed me to dissect the molecular and neural mechanisms underlying metabolic regulation. Moreover, the collaborative environment at UT Southwestern, especially working closely with Dr. Chen Liu, Dr. Joel Elmquist, and other experts in the field, has broadened my perspective on integrating molecular, circuit, and behavioral neuroscience. Engaging with leading researchers, presenting at international conferences, and receiving critical feedback have refined my ability to formulate impactful research questions. These experiences have solidified my aspiration to lead an independent research program focused on the neural mechanisms governing metabolism, ultimately guiding me toward a career in academia.

How has your basic research bridged the gap between lab discoveries and potential clinical applications?

My research explores how the brain regulates energy balance, specifically through the transcriptional control of Mc4r, a key gene in appetite and body weight regulation. By identifying orthopedia (OTP) as a critical regulator of Mc4r expression, my work has provided insights into a previously unrecognized genetic cause of obesity. Notably, our collaborator, Professor Sadaf Farooqi's team, has identified several OTP coding variants in children with severe obesity. To bridge the gap between basic research and clinical applications, I developed a mouse model carrying an OTP mutation found in these patients. These mice exhibited similar metabolic disturbances, confirming OTP’s role in body weight regulation. Importantly, treatment with the FDA-approved Mc4r agonist, setmelanotide, reversed obesity in these mice, suggesting a potential therapy for individuals with OTP mutations. This work was published in Science Translational Medicine (Xu et al., 2025). By uncovering a novel genetic pathway influencing obesity, my research not only advances our fundamental understanding of metabolic regulation but also opens the door for targeted treatments. This translational aspect of my work highlights how basic science can directly inform strategies to combat human metabolic diseases.

What unexpected discovery or challenge did you encounter in your basic research, and how did it shape your approach to scientific inquiry?

The most interesting part of my research has been the unexpected discoveries, as they open up numerous new possibilities. While studying the role of OTP in the hypothalamus, I found that it not only significantly regulates Mc4r expression but also affects oxytocin, a key molecule in social behaviors, with potential implications for autism spectrum disorders. This discovery presents a challenge, as it requires me to broaden my research focus to include social behaviors and deepen my expertise in autism spectrum disorders, which will be essential for understanding the underlying pathways. As a result, this finding has expanded the scope of my research, revealing an unexpected link between metabolic regulation and neurodevelopmental disorders, prompting me to further explore these connections in future studies.

How did participating in the Seldin Symposium impact your research path? 

The Seldin Symposium gave me an opportunity to present my work to a diverse audience of experts in the field of metabolism and internal medicine that was invaluable. It not only allowed me to receive constructive feedback on my research but also provided a platform for engaging with other researchers who are exploring similar questions related to energy balance and obesity. Additionally, the symposium fostered potential collaborations that could help expand the scope of my research, including clinical applications. The exposure to cutting-edge research and the chance to discuss my work with leading researchers gave me clarity on how to refine my research approach and pushed me to think more critically about the broader implications of my findings. It was also an excellent opportunity to build my professional network and establish connections that may help shape the future directions of my work.

What are your current research interests and goals?

My current research focuses on understanding how OTP regulates oxytocin expression and its role in social behavior. Oxytocin is a key neuropeptide involved in social bonding, emotional regulation, and communication, with strong implications for neurodevelopmental disorders such as autism spectrum disorders. To investigate the physiological role of OTP in oxytocin neurons, I am studying mice with targeted deletion of OTP in these neurons. By combining genetic, molecular, and behavioral approaches, my goal is to uncover the mechanisms through which OTP influences oxytocin-mediated social behaviors. This research may provide insights into the neural basis of social deficits and contribute to potential therapeutic strategies for neurodevelopmental disorders such as autism.

What advice would you offer for current Internal Medicine trainees about pursuing research?

Embrace curiosity. Start by identifying areas within your clinical work that spark your interest. Research can be challenging, but it also provides unique opportunities to ask questions that have the potential to change how we understand and treat diseases. Also, actively seek mentorship and collaborate with others, as science is rarely a solo endeavor. Don’t be afraid to step out of your comfort zone and explore new methods or technologies, as this will expand your skill set and open new avenues of discovery. Finally, and most important, be persistent. Research may not always yield immediate answers, but the journey itself is often just as valuable as the discoveries that emerge.

Representative Publications

"The Seldin Symposium gave me an opportunity to present my work to a diverse audience of experts in the field of metabolism and internal medicine that was invaluable."

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