Biology of Torpor and Hibernation
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, hibernation, and cryobiosis. 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 from various organisms adapt to function at low temperatures, 3) how tardigrades evolved to survive cycles of freezing and thawing, and 4) the applications of these states to slowing down tissue damage, disease progression, aging, and cryopreservation. Our long-term goal is to explore potential applications of inducing similar states of “suspended animation” in humans.
Neuronal Regulation and Physiology
How do animals initiate profoundly hypothermic and hypometabolic states such as torpor and hibernation? Building on our discovery of neurons that regulate mouse torpor, we are exploring a) how torpor-regulating neurons receive information about the body’s energy-state, and b) how these neurons act to alter whole-body metabolism and body temperature.
Hrvatin et al. Nature 2020
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.
Lam, Kajderowicz et al. eLife 2024
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.
Jayne et al. Nature Aging 2025
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.
Hrvatin et al. eLife 2019
Nagy et al. PNAS 2024
Freeze Tolerance
We explore the fascinating survival mechanisms of tardigrades, tiny water-dwelling creatures, often called “water bears”. These animals are renowned for their resilience to extreme conditions, such as severe dryness, freezing temperatures, high radiation, and even the vacuum of space. One of their most remarkable abilities is cryobiosis – the capacity to survive being frozen at temperatures as low as -196°Celsius, perhaps the closest natural phenomenon to the science fiction concept of “suspended animation”. We are learning from these remarkable organisms how to develop novel approaches towards human cell, tissue, and organ preservation.
Team Members
Siniša Hrvatin
Principal Investigator
Eric Griffith
Research Associate
Sumiko Williams
Administrative Lab Manager
Michael Chen
Graduate Student
Alanna Cheng
Graduate Student
Juliana Fox
Graduate Student
Philip Hwang
Postdoctoral Fellow
Aellah Kaage
Graduate Student
Karina Lezgiyeva
Postdoctoral Fellow
Aleksandar Markovski
Graduate Student
Adrian Martinez
Graduate Student
Manuel Martinez
UROP
Christopher Reid
Postdoctoral Fellow
Tara Thakurta
Graduate Student
Alumni
Matthew Alkire
Research TechnicianMatias Andina
Graduate StudentKathrin Kajderowicz
Graduate StudentAndrew Lee
Postdoctoral FellowWenhui Li
Research TechnicianNathan Nigrin
Research TechnicianNanako Kuze
UROPCurrently completing a BS in Biology and Computer Science at MIT
Breanna Lam
Graduate StudentAurora Lavin-Peter
Lab ManagerCurrently a JD student at UNC School of Law
Lorna McElrath
Research TechnicianCurrently a Neuroscience PhD student at Stanford University
Simon Opsahl
UROPCurrently completing a BS in Electrical Engineering and Computer Science at MIT
Sarah Park
UROPCurrently completing a BS in Biology at MIT
Julian Roessler
Graduate StudentCurrently a postdoctoral associate in the lab of Dr. Daniel Mucida at The Rockefeller University
Audrey Wang
UROPCurrently a Neuroscience PhD student at Columbia University
Richard Zayas
UROPLab News
Selected Publications
- Jayne, L., Lavin-Peter, A., Roessler, J., Tyshkovskiy, A., Antoszewski, M., Ren, E., Markovski, A., Sun, S., Yao, H., Sankaran, V.G., Gladyshev, V.N., Brooke, R.T., Horvath, S., Griffith, E.C., Hrvatin, S.
A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan. Nat Aging 5, 437–449 (2025). https://doi.org/10.1038/s43587-025-00830-4 - Lam, B., Kajderowicz, K.M., Keys, H.R., Roessler, J.M., Frenkel, E.M., Kirkland, A., Bisht, P., El-Brolosy, M.A., Jaenisch, R., Bell, G.W., Weissman, J.S., Griffith, E.C., Hrvatin, S.
Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death. eLife 13:RP102310 (2024). https://doi.org/10.7554/eLife.102310.1 - Nagy, M.A., Price, S., Wang, K., Gill, S.P., Ren, E., McElrath, L., Pajak, V., Deighan, S., Liu, B., Lu, X., Diallo, A., Lo, S.-C., Kleiman, R., Henderson, C., Suh, J., Griffith, E.C., Greenberg, M.E., Hrvatin, S.
Cis-regulatory elements driving motor neuron-restricted viral payload expression within the mammalian spinal cord. Proc. Natl. Acad. Sci. U.S.A. 121 (49) e2418024121 (2024). https://doi.org/10.1073/pnas.2418024121 - Hrvatin, S., Sun, S., Wilcox, O.F., Yao, H., Lavin-Peter, A.J., Cicconet, M., Assad, E.G., Palmer, M.E., Aronson, S., Banks, A.S., Griffith, E.C., Greenberg, M.E.
Neurons that regulate mouse torpor. Nature 583, 115–121 (2020). https://doi.org/10.1038/s41586-020-2387-5 - Hrvatin, S., Tzeng, C.P., Nagy, M.A., Stroud, H., Koutsioumpa, C., Wilcox, O.F., Assad, E.G., Green, J., Harvey, C.D., Griffith, E.C., Greenberg, M.E.
A scalable platform for the development of cell-type-specific viral drivers. eLife 8, e48089 (2019). https://doi.org/10.7554/eLife.48089 - Hrvatin, S., Hochbaum, D.R., Nagy, M.A., Cicconet, M., Robertson, K., Cheadle, L., Zilionis, R., Ratner, A., Borges-Monroy, R., Klein, A.M., Sabatini, B.L., Greenberg, M.E.
Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neurosci 21, 120–129 (2018). https://doi.org/10.1038/s41593-017-0029-5
Contact
Hrvatin Lab
Whitehead Institute for Biomedical Research
Room 661C (Office), Room 611 & 613 (Labs)
455 Main Street
Cambridge, MA 02142-1479
Tel: 617-258-9243 (Office), 617-258-5067 (Lab)
Email: hrvatin_admin@wi.mit.edu
