Research Interests

Molecular biology of mammalian hibernation

Research in my laboratory is directed toward the characterization of genes and small molecules responsible for the induction and maintenance of hibernation in mammals. Hibernation is seen in a wide-range of taxa including rodents, carnivores, insectivores, bats and even primates. Since the majority of species within these groups do not hibernate, it has been proposed that hibernation results from differential expression of genes common to all mammals, rather than the evolution of new genes unique to the hibernating species. We have used RNAseq and proteomics to identify genes and proteins that are responsible for the physiological characteristics of hibernation in the thirteen-lined ground squirrel Ictidomys tridecemlineatus.

During hibernation body temperature is only a few degrees above 0^oC, oxygen consumption holds at 1/30 to 1/50 of the aroused condition and heart rate can be as low as 3-10 beats/minute, compared to 300-400 beats/minute when the animal is active. Mechanisms by which hibernators avoid injury from these extremes are of great biomedical interest because of potential applications in the areas of traumatic brain injury, myocardial infarction, organ preservation, hemorrhagic shock and stroke. We have developed a hibernation-based therapy for hemorrhagic shock and are currently using hibernation strategies to develop new methods for organ preservation. Improvements in preserving donor organs has potential for increasing organ availability for patients on transplant waiting lists worldwide.

Publications

Abid MSR, Bredahl EC, Clifton AD, Qiu H, Andrews MT, and Checco JW. (2023) Proteomic Identification of Seasonally Expressed Proteins Contributing to Heart Function and the Avoidance of Skeletal Muscle Disuse Atrophy in a Hibernating Mammal. J. Proteome Res., https://doi.org/10.1021/acs.jproteome.3c00540.

Heinis FI, Alvarez S and Andrews MT (2023), Mass spectrometry of the white adipose metabolome in a hibernating mammal reveals seasonal changes in alternate fuels and carnitine derivatives. Front. Physiol. 14:1214087. doi: 10.3389/fphys.2023.1214087

Heinis FI, Alvarez S, Rugira K, McMurchie A, Schuster O, Andrews MT (2023). Seasonal changes in the metabolomic profile of white adipose tissue in hibernating thirteen-lined ground squirrels, Physiology 38 (S1), 5734478. American Physiological Society Summit, April 19-23, 2023. Long Beach, CA.

Mousavi S, Qiu H, Heinis FI, Bredahl EC, Abid MSR, Clifton AD, Andrews MT, and Checco JW. (2023) Effects of Anesthetic Administration on Rat Hypothalamus and Cerebral Cortex Peptidome. ACS Chem Neurosci. 14, 3986-3992.

Mousavi S, Qiu H, Heinis FI, Abid MSR, Andrews MT, and Checco JW. (2022) Short-term administration of common anesthetics does not dramatically change the endogenous peptide profile in the rat pituitary. ACS Chem Neurosci., 13(19), 2888-2896. https://doi.org/10.1021/acschemneuro.2c00359

Andrews, M.T. (2019) Molecular interactions underpinning the phenotype of hibernation in mammals. J Exp Biol. 222, jeb160606.

Ballinger, M.A. and Andrews, M.T. (2018) Nature's fat-burning machine: brown adipose tissue in a hibernating mammal. J Exp Biol. 221, jeb162586.

Oliver, S.R., Anderson, K.J., Hunstiger, M.M., and Andrews, M.T. (2018) Turning down the heat: down-regulation of sarcolipin in a hibernating mammal. Neuroscience Letters 10.1016/j.neulet.2018.11.059.

Ballinger, M.A., Schwartz, C., and Andrews, M.T. (2017) Enhanced oxidative capacity of ground squirrel brain mitochondria during hibernation. Am J Physiol. 312, R301-R310.

Perez de Lara Rodriguez, C.E., Drewes, L.R., and Andrews, M.T. (2017) Hibernation-based blood loss therapy increases survivability of lethal hemorrhagic shock in rats. J Comp Physiol B. 187, 769-778.

Anderson, K.J., Vermillion, K.L., Jagtap, P., Johnson, J.E., Griffin, T.J., and Andrews, M.T. (2016) Proteogenomic analysis of a hibernating mammal indicates contribution of skeletal muscle physiology to the hibernation phenotype. J. Proteome Res., 15, 1

Ballinger, M.A., Hess, C., Napolitano, M.W., Bjork, J.A., and Andrews, M.T. (2016) Seasonal changes in brown adipose tissue mitochondria in a mammalian hibernator: from gene expression to function. Am J Physiol., 311, R325-336.

Cooper, S.T., Sell, S.S., Fahrenkrog, M., Wilkinson, K., Howard, D.R., Bergen, H., Cruz, E., Cash, S.E., Andrews, MT, and Hampton, M. (2016) Effects of hibernation on bone marrow transcriptome in thirteen-lined ground squirrels. Physiol Genomics 48, 513-

Heinis, F.I., Vermillion, K.L., Andrews, M.T. and Metzger, J.M. (2015) Myocardial performance and adaptive energy pathways in a torpid mammalian hibernator. Am. J. Physiol., 309, R368-377.

Schwartz, C., Ballinger, M.A. and Andrews M.T. (2015) Melatonin receptor signaling contributes to neuroprotection upon arousal from torpor in thirteen-lined ground squirrels. Am. J. Physiol., 309, R1292-1300.

Schwartz, C., Hampton, M. and Andrews, M.T. (2015) Hypothalamic gene expression underlying pre-hibernation satiety. Genes, Brain and Behavior, 14, 310-318.

Vermillion, K.L., Anderson, K.J., Hampton, M. and Andrews, M.T. (2015) Gene expression changes controlling distinct adaptations in the heart and skeletal muscle of a hibernating mammal. Physiol. Genomics, 47, 58-74.

Vermillion, K.L., Jagtap, P., Johnson, J.E., Griffin, T.J., and Andrews, M.T. (2015) Characterizing cardiac molecular mechanisms of mammalian hibernation via quantitative proteogenomics. J. Proteome Res., 14, 4792-4804.