Current research in the Carey Laboratory focuses on gastrointestinal and liver physiology in hibernating mammals. We study basic aspects of organ function during the seasonal hibernation cycle, and also use hibernators as models for endogenous protection against stress and trauma conditions, including organ cold storage, ischemia/reperfusion injury and seasonal fattening. Our current studies include metabolomic analysis to identify biomarkers of seasonal metabolic cycles in liver, plasma and brain; examination of gene expression and signaling pathways involved in cholesterol and lipid metabolism in gut and liver; and the role of the gut microbiota in hibernation.

In addition to discovering novel aspects of hibernation biology at the physiological and molecular levels, our research is designed to translate insights gained from the hibernation phenotype to improvements in human and animal biomedicine.

Summaries of Recent Projects:

Analysis of the seasonal hibernation cycle using LC-MS based metabolomics. Lab member: Clark J. Nelson, Ph.D.
This project uses a discovery-based approach to characterize the hibernation phenotype via changes in small molecule levels in ground squirrels. Current studies use liver, plasma and brain tissue to track metabolite changes in the active and hibernation seasons, and in distinct torpor-arousal states in winter.

Gene expression and signaling pathways in cholesterol and lipoprotein metabolism in hibernation. Lab member: Jessica P. Otis, B.S.
Mammalian hibernators switch from a carbohydrate-based to a lipid-based metabolism during the long winter fast of hibernation. Plasma cholesterol levels increase about 2-fold during the winter months, but the mechanisms responsible for this change and its functional role in hibernator physiology are poorly understood. This project examines gene expression and signaling pathways related to cholesterol, lipoprotein and bile acid metabolism in ground squirrels during the seasonal cycle of feeding and fasting.

The gut microbial community in mammalian hibernation:
The overall goal of this project is to understand how seasonal cycles of feeding and fasting in a mammalian hibernator affect the resident gut microbiota and its metabolic output, and how host responses maintain a healthy relationship with the microbiota. The host diet is one of the major determinants of microbiota composition and its metabolic output, but little is known of how the microbiota is affected in host species that undergo long periods with no food intake. Hibernation is the most dramatic and best studied model of long-term fasting in mammals, which makes it an ideal natural system in which to examine this issue. Through their ability to degrade endogenous host substrates, gut microbes have the potential to influence energy and nutrient balance during the hibernation season. However, chronic fasting can compromise the host’s intestinal barrier that maintains the microbiota safely in the intestinal lumen. This project examines how hibernation affects the numbers, composition and metabolic output of the gut microbiota and in turn, how the hibernator host maintains its partnership with gut symbionts through enhanced immune defenses. We use culture-independent methods to assess seasonal changes in the gut microbial community through collaboration with the Handelsman Lab at UW-Madison.