The ASPIRE Path in Molecular Medicine

My project in the Ayala Lab focuses on investigating the molecular mechanisms mediating the weight loss effects of GLP1R agonists. We have identified a novel interaction between two proteins – PKA and mTORC1 – contributing to the anorectic effects of GLP1R drugs such as Liraglutide and Semaglutide. As a neuroscientist in training, I am interested in investigating this pathway in GLP1R-expressing POMC neurons in the Arcuate Nucleus of the Hypothalamus and whether this regulates a functional circuit between the Arcuate Nucleus and the Paraventricular Nucleus of the Hypothalamus. Both the Arcuate Nucleus and Paraventricular Nucleus regulate food intake by increasing satiety and reducing hunger.

A two-pronged approach to study this novel pathway downstream of GLP1R activation specifically in the context of brain-control of weight loss and obesity will not only provide insight into the mechanistic nuances of GLP1R agonist drugs but also help inform us of new therapeutic approaches to increase the efficacy of these drugs. My research plans are clinically focused on elucidating how this novel pathway contributes to obesity and weight loss observed upon GLP1R agonist treatment. I hope to learn all clinical aspects of the diseased state I study so as to contextualize my work in a relevant useful clinical setting.