I am a comparative and evolutionary physiologist with a strong interest in the physiological mechanisms underlying gas exchange in vertebrates. Specifically, I study physiological mechanisms and compromises between gas exchange, acid/base-regulation, and neural function. In my research, I use the retina within the eye as a model organ, as this is the most metabolically active tissue in the body but lacks blood vessels (to avoid light scattering), providing an ideal model organ to understand limitations and compromises to gas exchange in tissues. Here, I integrate methodologies from cardiorespiratory- and electro-physiology with cutting-edge OMICs tools to understand how oxygen diffuses in tissues and how metabolic processes and tissue functions change along O2 diffusion gradients. To investigate this, I integrate tissue O2 profiling, electrophysiological recordings, and spatial transcriptomics to understand tissue function at high spatial resolution. These approaches allow me to obtain an integrative understanding of physiological processes from the genomic to whole organismal level and understand how those processes differ in space within heterogeneous organs.
In addition to using the classic single-species approach to understand integrative physiological mechanisms, my research also appreciates the physiological diversity between species and applies phylogenetic comparative methods to address how complex physiological traits have originated, diversified, and interacted across macroevolutionary timescales. Thus, instead of using a single model organism in my studies, I select a model clade - i.e., a group of phylogenetically related species that differ with respect to the trait of interest, and I apply the same experimental methods to all species within the clade. Using information about the species’ phylogenetic relationship, I can then identify how physiological systems changed in the phylogenetic intervals that bracket major transitions in animal evolution. This multi-species approach to physiology allows me to understand the evolution of respiratory systems, the compromises between gas exchange and other physiological functions, and how those tradeoffs have been prioritized during animal evolution.
Below you can read about specific ongoing projects in the lab:
Cellular Function at Respiratory Extremes in the Fish Retina
Oxygen delivery and the removal of waste products are essential for cellular function. In the fish retina, however, these processes occur under extreme conditions, where oxygen and proton levels are ten times higher than in most other tissues. Such conditions would be lethal for most animal cells, yet the fish retina thrives in this environment. This line of research aims to uncover the cellular mechanisms that allow fish retinal cells to function under these extreme respiratory conditions.
Specifically, we are investigating three key processes: how blood acidification drives oxygen release to the retina, how retinal cells regulate their pH in such acidic environments, and how they protect themselves from oxidative damage caused by the high oxygen levels. Using a combination of in vivo oxygen and pH measurements, spatial transcriptomics, and cutting-edge bioimaging techniques, we aim to reveal the cellular adaptations that support survival at the very limits of physiological function.
Hypoxia Tolerance in the Bird Retina
Birds possess avascular retinas, lacking the internal blood vessels typically found in the eyes of other vertebrates. This presents unique challenges for oxygen delivery, particularly during high-altitude flights when oxygen levels are significantly reduced. Our project aims to understand how birds meet the energy demands of the retina conditions of no blood perfusion and oxygen deprivation.
We are investigating how retinal cells adapt to low-oxygen environments, focusing on glucose transport, energy production through anaerobic metabolism, and waste product removal. To explore these mechanisms, we use techniques such as in vivo oxygen profiling, spatial and single-cell transcriptomics, and mitochondrial respirometry. These approaches allow us to map oxygen distribution, analyze gene expression at high spatial resolution, and measure mitochondrial function, offering insights into the adaptations that enable birds to sustain visual function in extreme environments.
Retinal Vascularization and Metabolism in Mammals
We are using molecular tools to understand how changes in retinal vascularization affect metabolism and function in mammals. By studying retinal development in mice, we explore how vascularization development affects metabolic processes during early life stages. We also investigate how hibernation affects retinal metabolism in ground squirrels, focusing on the metabolic shifts that occur during hypothermia and metabolic depression. Additionally, we examine how evolutionary reductions in retinal vascularization across different mammalian species impact retinal function and metabolism. This line of research seeks to uncover the molecular mechanisms linking vascularization to retinal metabolism across time scales.
