Jane Reznick

FM | CECAD

Research Areas

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Evolutionary Strategies for Health and Regeneration

At ages far beyond their expected lifespan, naked mole-rats fail to exhibit any standard sign of physiological decline achieving lifespans of  >35 years. Hence, this mammal provides a proof-of-concept that age-related health decline can be avoided.

Research Focus

Injured cardiac tissue compared to uninjured tissue in naked mole-rat showing markers of regeneration.
Injured cardiac tissue compared to uninjured tissue in naked mole-rat showing markers of regeneration.

As a subterranean mammal, the naked mole-rat faces a particularly challenging environment characterized by patchily available food, low O2 and high CO2 levels. In response naked mole-rats have evolved a suite of molecular and physiological adaptations that we believe offer this animal pleiotropic protection against age-dependent decline.

Our lab is primarily interested in two major aspects of naked mole-rat physiology - its rapid response and adaptation to external stress and its ability to repair and regenerate tissue.

Naked mole-rats give us unique insights into molecular strategies that evolution utilizes to resist or repair cellular damage. Our challenge now is to discover, understand and harness these strategies for human health.

Our Goals

Untargeted metabolomic screen reveals a distinct metabolic response to ischaemia in naked mole-rats compared to mice in liver and heart. Alternative metabolic routes used by naked mole-rats give valuable insights into protective mechanisms resisting disease and promoting healthspan.
Untargeted metabolomic screen reveals a distinct metabolic response to ischaemia in naked mole-rats compared to mice in liver and heart. Alternative metabolic routes used by naked mole-rats give valuable insights into protective mechanisms resisting disease and promoting healthspan.

We use a comparative approach between naked mole-rat and mouse to investigate metabolic plasticity and epigenetic rewiring accompanying changes in oxygen, nutrient levels and injury.

  • Metabolic Plasticity. Via extensive metabolomic and transcriptomic screens, we have identified several rerouted metabolic pathways and signalling molecules which give naked mole-rats an adaptive advantage to protect, function and repair in the face of stress and injury. Our goal is to understand the significance of these alternative metabolic processes and test them in relevant transgenic mouse models. 
     
  • Epigenetic Rewiring. We interrogate evolutionary adaptations encoded in the genome and changes in epigenetic landscapes which give rise to unique physiological traits and plasticity in naked mole-rats.
     
  • Regeneration. Preliminary results indicate the naked mole-rat is a regenerative mammal. We are establishing cardiac regeneration and skin wound repair models in naked mole-rats to couple with spatial omic technology and interrogate mechanisms of healthy regeneration.

Key Publications

  1. Reznick J, Park TJ, Lewin GR. A Sweet Story of Metabolic Innovation in the Naked Mole-Rat. Adv Exp Med Biol. (2021). 1319:271-286. doi: 10.1007/978-3-030-65943-1_10.
     
  2. Park TJ*, Reznick J*, Peterson BL, Blass G, Omerbašić D, Bennett NC, Kuich PHJL, Zasada C, Browe BM, Hamann W, Applegate DT, Radke MH, Kosten T, Lutermann H, Gavaghan V, Eigenbrod O, Bégay V, Amoroso VG, Govind V, Minshall RD, Smith ESJ, Larson J, Gotthardt M, Kempa S, Lewin GR. Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat. Science. (2017) 356(6335):307-311. doi: 10.1126/science.aab3896. *equal contribution
     
  3. Eigenbrod O*, Debus KY*, Reznick J, Bennett NC, Sánchez-Carranza O, Omerbašić D, Hart DW, Barker AJ, Zhong W, Lutermann H, Katandukila JV, Mgode G, Park TJ, Lewin GR. Rapid molecular evolution of pain insensitivity in multiple African rodents. Science. (2019) 364(6443):852-859. doi: 10.1126/science.aau0236. *equal contribution

Research Areas

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3