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Li Li, Ph.D.

Basic Science Award, 2023

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

UT Southwestern is known worldwide for its high-quality science, distinguished faculty, and excellence in education and training, especially in metabolism. During my five-year training in the labs of Drs. Chen Liu and Joel Elmquist, I had the opportunity to immerse myself in neuroscience research despite having limited prior experience.

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

My research aims to understand the mechanisms that regulate energy balance. Although GLP1 analogs have been widely used for obese treatment. Unfortunately, 10 to 20 percentof patients fail to achieve minimal weight loss (5 percent). I discovered that triptans, a class of commonly prescribed migraine medications, have unexpected appetite-suppressing effects. This finding highlights a potential new, cost-effective strategy for obesity treatment and underscores the importance of exploring existing drugs for novel therapeutic applications.

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

The serotonin (5-HT) system has been a focal point for multiple weight-loss medications for decades. The therapeutic potential of this pathway was highlighted by the observation that the anorectic effect of d-fenfluramine, the active ingredient of the once-popular diet pill Fen/Phen, was partially mediated through its activation of 5-HT2C (Htr2c) receptors in the brain.

In the search for new weight-loss therapies based on the 5-HT pathway, I discovered that agonists for the 5-HT 1B receptor (Htr1b) dose-dependently reduced food intake in C57BL/6 mice. These include several triptans, a class of commonly prescribed migraine drugs that manifest few health risks after long term use. Moreover, I demonstrated that the expression of Htr1b in NPY/AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) was necessary for the appetite-suppressing effect of triptans.

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

Receiving the Basic Science Award was an incredible honor. The Seldin Symposium provided a platform to present my research, receive valuable feedback from faculty and peers, and connect with potential collaborators. It reinforced the importance of clear scientific communication and helped shape the direction of my future studies.

What are your current research interests and goals?

I found that Htr1b-expressing NPY neurons in the ARH, which mediate the appetite-suppressing effects of triptans, are located outside of the blood-brain barrier (BBB). This raised the possibility that these neurons would be anatomically positioned to survey levels of circulating 5-HT. My current research focuses on understanding how Htr1b-expressing NPY neurons integrate gut 5-HT signal and its subsequent effects on energy balance.

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

Effective time management and regular progress review are essential for pursuing research. Additionally, embracing challenges and staying open to unexpected findings can lead to exciting new discoveries.

Representative Publications

"The Seldin Symposium provided a platform to present my research, receive valuable feedback from faculty and peers, and connect with potential collaborators."

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