Jonathan Long, PhD, Stanford University, Webinar

Moderator: Jonathan Long, Ph.D., Assistant Professor of Pathology, Sarafan ChEM-H, Stanford University

Webinar title: Chemical control of mammalian physiology.

Abstract: Chemical messengers mediate intercellular communication and control physiologic homeostasis. Historically, much of the work in area has focused on a small handful of molecules, such as catecholamines, steroid hormones, and neurotransmitters. With modern mass spectrometry, it is now recognized that there are likely many more bioactive molecules than previously recognized. Here, we share our recent progress understanding the chemistry and biology of a large class of orphan blood-borne signaling metabolites called N-acyl amino acids. We will discuss our de-orphanization of Lac-Phe and other N-lactoyl amino acids which constitute lactate-derived signaling metabolites that control feeding and obesity. We also describe ongoing work on BHB-Phe, an orphan metabolite derived from the ketone body beta-hydroxybutyrate. Ketosis-inducible BHB-Phe is a congener of exercise-inducible Lac-Phe and regulates energy balance in ketosis. These studies uncover and unexpected and underappreciated role for amino acid derivatives as chemical messengers in energy balance and physiology.

Presenters:

Veronica Li is a fourth-year PhD student at Stanford University working with Professor Jonathan Long where she studies the molecular mechanisms that mediate the systemic benefits of physical activity. During her graduate work, Veronica discovered a novel exercise-induced metabolite called Lac-Phe that reduces food intake and body weight. This molecule is increased with exercise in not only mice but also in humans and racehorses, establishing it as a robust exercise inducible metabolite across several mammalian species. Conversely, mice that are genetically depleted in Lac-Phe have increased food intake and body weight when exercised. Overall, this work has de-orphanized a novel exercise-induced metabolite that functions to regulate feeding and energy balance.

Maria Dolores Moya-Garzon is a postdoctoral fellow in the Long Lab, where she is studying the chemical dissection of physiological and nutritional ketosis. She performed her PhD studies in Medicinal Chemistry with Professor Monica Diaz-Gavilan at the University of Granada, where she developed double glycolate oxidase/lactate dehydrogenase inhibitors for the treatment of Primary Hyperoxaluria type 1. Subsequently, she was awarded the Alfonso Martin Escudero postdoctoral fellowship to join the lab of Jonathan Long at Stanford University to work on the identification and functional interrogation of novel ketosis-induced bioactive metabolites.