Hrvatin Lab

To survive extreme environments, many animals have evolved the ability to profoundly decrease metabolic rate and body temperature and enter states of dormancy, such as torpor and hibernation. The laboratory studies the mysteries of how animals and their cells initiate, regulate, and survive these adaptations. Specifically, we focus on investigating: (1) how the brain regulates torpor (in mice) and hibernation (in hamsters), (2) how cells and genomes of different organisms adapt to these states, and 3) whether inducing these states can slow down tissue damage, disease progression, and even aging. The long-term goal is to explore potential applications of inducing similar states of “suspended animation” in humans.

Neuronal Regulation and Physiology -- To survive extreme environments, many animals have evolved the ability to profoundly decrease metabolic rate and body temperature and enter states of dormancy, such as torpor and hibernation. Our laboratory studies the mysteries of how animals and their cells initiate, regulate, and survive these adaptations. Specifically, we focus on investigating: 1) how the brain regulates torpor (in mice) and hibernation (in hamsters), 2) how cells and genomes of different organisms adapt to these states, and 3) whether inducing these states can slow down tissue damage, disease progression, and even aging. Our long-term goal is to explore potential applications of inducing similar states of “suspended animation” in humans.

Cellular Adaptations -- Cells from hibernating organisms have evolved the ability to survive extreme cold temperatures for many weeks to months. Using genetic screens we’re investigating the species-specific mechanisms of extreme cold tolerance and exploring whether these mechanisms can be induced in non-hibernating organisms including humans.

Aging, Disease, and Applications -- It has long been known that hibernators live longer than closely related non-hibernators, that cancer cells do not replicate during hibernation, and that hypothermic states are neuroprotective during hypoxic/ischemic injury. The mechanisms behind these observations, however, remain a mystery. By inducing a long-term hibernation-like state in mice and natural hibernation in hamsters, we are examining the effects of these states on aging, lifespan, tissue repair, and progression of cancer.

Technology: Cell Type Specific Viruses -- A lack of tools to access defined cell types is a major impediment to efforts to study brain function including behaviors such as torpor and hibernation. To address this issue, we developed the PESCA (Parallel Enhancer Single Cell Assay) platform for screening of enhancers that drive cell-type-specific expression from adeno-associated viruses (AAVs) enabling genetic access to individual cell types in mice, hibernators, as well as primates. We are using PESCA to develop neuroscience tools, and collaborating with biopharma to develop new targeted human gene therapies.