Maria Dolores Moya-Garzon
Dr. Maria Dolores Moya-Garzon, Pfizer-University of Granada Centre for Genomics and Oncological Research
Harnessing BHB-amino acids: a novel family of physiologically relevant ketone metabolites
Bio
Dr. Maria Dolores Moya-Garzon is the Group Leader of the Nutrition and Metabolic Regulation in Disease Lab at the Pfizer-University of Granada Centre for Genomics and Oncological Research in Spain.
During her postdoctoral training at Stanford University in Jonathan Long’s lab, she discovered a family of bioactive ketone metabolites called BHB-amino acids. These studies characterized BHB-amino acids as endogenous metabolites in mice and humans that rise in response to ketosis and regulate energy balance and feeding behavior.
Building on this work, and in collaboration with Dr. Juliet Knowles’ lab, they are now exploring whether BHB-amino acids can promote brain health, with a particular focus on their potential role in the anti-seizure effects of ketogenic diet in epilepsy.
As an independent investigator, her research is now expanding the study of BHB-amino acids into inflammation, cancer, and metabolic disease. Her work aims to define the molecular mechanisms and biological functions of these metabolites with the goal of identifying new opportunities to therapeutically harness this novel ketone pathway.
Abstract
Ketosis is a physiological state induced by carbohydrate restriction, in which the liver produces ketone bodies, primarily β-hydroxybutyrate (BHB), that serve as alternative metabolic fuels. Although ketosis has long been recognized for its therapeutic potential in particular contexts, the molecular mechanisms underlying its effects remain incompletely understood. We discovered that the enzyme CNDP2 conjugates BHB with amino acids to generate BHB-amino acids, a novel family of endogenous metabolites conserved in mice and humans that increase in blood during ketosis. We found that these metabolites, particularly BHB-phenylalanine (BHB-Phe), regulate energy balance and suppress food intake in mice. Building on these findings, we are now investigating their potential role in brain health and their contribution to the anti-seizure effects of ketogenic diets in epilepsy.
Annie Goettemoeller
Dr. Annie Goettemoeller, Postdoctoral Researcher, Soltesz Lab, Department of Neurosurgery, Stanford University
Vulnerability of Entorhinal-Dentate Gyrus Circuit Communication in Alzheimer's disease
Bio
Dr. Goettemoeller is a postdoctoral researcher in the Soltesz Lab at Stanford University. Her research explores the functional specialization of hippocampal inhibitory circuits, spanning synaptic physiology, circuit connectivity, and in vivo network dynamics. Using patch-clamp electrophysiology alongside in vivo silicon-probe recordings and voltage imaging, she investigates how distinct interneuron populations coordinate brain states and how these circuits become vulnerable in Alzheimer’s disease.
Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease, yet current treatments are unable to prevent its initiation and progression. Although brain regions of early vulnerability have been known for over 30 years, how the disease propagates from these regions throughout the rest of the brain remains unclear. Within the cortex, the Entorhinal Cortex (EC) is noted as one of the most vulnerable regions in Alzheimer’s disease, displaying prominent pathologies and severe neurodegeneration early in disease progression. Interestingly, recent research has focused on the role of physiological dysfunction in AD, which has also been suggested to arise early in the EC. Furthermore, it has been suggested that EC physiological dysfunction is either a cause or catalyst for propagation of AD-related pathology spreading into the hippocampus and, ultimately, throughout the rest of the brain. As the EC provides critical input to the dentate gyrus (DG), disruption of EC-DG communication may represent an important early mechanism linking circuit dysfunction to memory impairment and disease progression. Here, we explore how early changes in EC-DG circuit function may contribute to AD pathophysiology. Understanding how these circuit dynamics become disrupted may provide insight into how early physiological dysfunction contributes to cognitive impairment and identify opportunities for restoring circuit function before widespread neurodegeneration occurs.
About the Series
The first Monday of each month, the Knight Initiative for Brain Resilience will host monthly seminars to bring together awardees, affiliated professors and students for a series of talks. Two speakers will discuss their brain resilience research, experiences in the field, and answer questions about their work.
To support our researchers' participation, these seminars are not streamed/recorded and are only open to members of the Stanford community.