We currently dedicate our research to identifying neuronal populations that regulate liver function during dietary and infectious challenges. We are particularly motivated to discover the neurons at the blood-brain interface that detect peripheral signals and initiate counter-regulatory responses to environmental stressors, ensuring survival in a changing environment.
Understanding physiology through the lens of sex differences
Our research aims to uncover the reason as to why some diseases affect males and females differently, a phenomenon known as sex-biased diseases. Our recent work suggests that sex differences in disease prevalence and severity stem from sex-specific adaptations to environmental pressures, such as infections and food availability, which have evolved over time. However, in our modern, rapidly changing world, these ancient adaptations can lead to sex-biased diseases. Our research seeks to uncover sex-specific regulators of metabolic systems in order to design treatment strategies for conditions such as fatty liver, type 2 diabetes, and acute infections.
To achieve this goal, we conduct experiments in mice using dietary interventions and infections to reveal sex-specific responses in the liver and brain. The liver plays a critical role in maintaining glucose and lipid levels and metabolic homeostasis. The brain, meanwhile, helps the body adapt to environmental challenges by controlling peripheral organ function and releasing hormones that regulate metabolism and energy balance. By understanding how the liver and brain communicate, we may develop novel strategies to treat metabolic diseases.
Our current research focuses on testing the hypothesis that the molecular basis of sex-biased diseases can be partly explained by sex hormone signaling in the brain. Using neuroendocrinology methods, we study sex-specific neuronal responses to dietary challenges and infections. By identifying potential targets for therapeutic intervention, our work could help develop personalized treatments for sex-specific diseases and improve health outcomes for both males and females. Ongoing research projects in the lab include:
Enduring the extremes: unraveling the mechanisms behind female resilience to famine. This research project is founded on the observation that females display a markedly higher resilience to periods of food restriction, surviving famines substantially better than their male counterparts. Our aim is to dissect the mechanisms and adaptive strategies that underpin this significant difference in survival rates between the sexes.
Neurobiology of systemic lipid homeostasis. While much is known about neuronal mechanisms monitoring circulating glucose levels, the set points that control lipid metabolism are undefined. Given that mammalian lipid metabolism is highly dynamic, responding to changing environmental factors, such as food availability and infections, we believe that a neural mechanism must regulate circulating lipids. In this project, we aim to define this mechanism, uncovering a fundamental neuronal mechanism that regulates lipid homeostasis.
Neuronal mechanisms of host immune responses. In this project, we wish to define neuronal mechanisms that control host defense programs against pathogenic infections. As most organisms become anorexic shortly after infection, we speculate that neuronal mechanisms have evolved to control the metabolic shift from utilizing glucose as the primary source of fuel (fed state) to burning lipids (fasted state induced by infection-associated anorexia). As the liver is a central organ regulating systemic lipid metabolism, we explore the idea that the brain and liver orchestrate the metabolic shift during infections and wish to define neuronal and hepatic factors that control these programs, solidifying the brain-liver axis as an integral part of host defense mechanisms against infections.