Life has evolved remarkable strategies to survive conditions that would normally be incompatible with survival, including prolonged oxygen deprivation, extreme cold, metabolic arrest, and even suspended animation. Our laboratory is interested in uncovering the fundamental biological principles that enable cells and organisms to achieve these extraordinary states of stress resilience. We seek to understand how evolution has naturally solved the challenges of protecting tissues from injury, slowing aging, and preserving function under extreme physiological stress.
To address these questions, we combine the genetic power of Caenorhabditis elegans with the unique biology of naturally hibernating mammals, including Arctic ground squirrels. C. elegans can enter reversible suspended animation during anoxia and survive freezing that would be lethal to most multicellular organisms, while Arctic ground squirrels tolerate repeated episodes of profound hypothermia and dramatically reduced blood flow to the brain and heart during hibernation without lasting injury. By integrating genetics, physiology, cell biology, functional genomics, metabolomics, proteomics, and computational approaches, we identify conserved molecular mechanisms that enable these exceptional forms of resilience.
Our work has uncovered previously unrecognized pathways regulating metabolic adaptation, proton and ion homeostasis, lipid trafficking, organelle function, and stress resistance. We have also discovered that some resilience mechanisms originated through horizontal gene transfer from microbes and were evolutionarily co-opted to enhance animal survival under extreme environmental conditions. These findings illustrate how evolution continuously generates innovative biological solutions to physiological challenges.
Ultimately, our goal is to define the core molecular programs underlying dormancy, hibernation, suspended animation, and healthy aging, and to harness these principles through synthetic physiology and chemical biology. We envision developing strategies to safely induce hibernation-like protective states in human cells and tissues, with potential applications in organ preservation and transplantation, ischemia and stroke, neurodegenerative diseases, healthy aging, regenerative medicine, emergency medicine, and long-duration space exploration.
