 Hannah V. Carey, Ph.D.
Department of Comparative Biosciences
School of Veterinary Medicine
Madison, WI 53706
608-263-0418
FAX: 608-263-3926
careyh@svm.vetmed.wisc.edu
Emphasis Group:
Human Nutrition
Principal Research Interest:
There are three general areas of research currently ongoing in the laboratory: hibernation biology, modulation of enterocyte physiology by induction of the stress response, and intestinal physiology in piglets.
Research Summary:
Hibernation Biology
Dr. Carey's research over the past several years has focused on the changes in intestinal structure and function that occur over the annual cycle of a classic hibernator, the 13-lined ground squirrel, with specific emphasis on the effects of hibernation on intestinal transport physiology.
Stress proteins and hibernation. Mammals that hibernate provide a novel natural system with which to study the adaptive significance of stress proteins in vertebrates because of the extreme shifts in body temperature and metabolism that occur over the course of the annual cycle, as well as during the transitions between torpor and interbout euthermia during the hibernation season. In this project seasonal changes in expression of stress proteins in various tissue of 13-lined ground squirrels, and the functional significance of those changes for mammals that hibernate are studied. The lab is also examining seasonal changes in a stress-induced transcription factor, NF-kB. These studies focus on the intestine, a tissue that is highly sensitive to thermal and oxidative stress.
Organ preservation in hibernating ground squirrels. This is a collaborative project between Dr. Carey's laboratory and the laboratories of Jim Southard in the University of Wisconsin Department of Surgery, Division of Transplantation, and Sandy Martin in the Department of Cellular and Structural Biology, University of Colorado Health Sciences Center in Denver. The project examines the cold preservation properties of organs from hibernating ground squirrels as a natural model for superior tolerance to cold ischemic stress. The goal is to identify the physiological and biochemical differences between hibernating liver and the prototype rat liver, and use molecular approaches to determine what gene products differ in the two that may facilitate the superior tolerance abilities of hibernators.
Modulation of Enterocyte Physiology by Induction of the Stress Response
There is growing interest in the use of the stress response to reduce tissue damage during pathologic conditions and to induce tolerance to future, anticipated stressors. For example, non-lethal heat shock has been shown in a variety of cell types to inhibit release of pro-inflammatory molecules such as IL-1b, nitric oxide and TNFa. This effect has significant therapeutic potential, because upregulation of these and other pro-inflammatory mediators is thought to contribute to the deleterious effects of several systemic diseases, infectious states and trauma conditions such as shock and ischemia-reperfusion injury. The lab is now exploring how preconditioning via non-lethal heat shock rescues cellular responsiveness to pro-inflammatory mediators that is suppressed after acute thermal or chemical stress.
Intestinal Physiology in Piglets
The laboratory also studies intestinal physiology in neonatal piglets. Recent studies have included the roles of enteral nutrition and specific growth factors in regulating intestinal epithelial growth and transport function. Current projects focus on cellular mechanisms that mediate inflammatory pathways in piglet intestine, and the development of a piglet model for necrotizing enterocolitis.
Representative Publications
Fleck, C. and H.V. Carey. 2005. Modulation of apoptotic pathways in
intestinal mucosa during hibernation. Amer. J. Physiol. Regul. Integr.
Comp. Physiol 289: R586-R595.
Kurtz, C.C., S.L. Lindell, M.J. Mangino and H.V. Carey. 2006. Hibernation
confers resistance to intestinal ischemia-reperfusion injury. Amer. J.
Physiol. Gastrointest. Liver Physiol. 291:G895-901.
Kurtz, C.C. and H.V. Carey. 2007. Seasonal changes in the intestinal immune
system of hibernating ground squirrels. Develop. Comp. Immunol. 31:
415-428.
Serkova, N.J., J.C. Rose, L. E. Epperson, H.V. Carey and S.L. Martin. 2007.
Quantitative analysis of liver metabolites in three stages of the circannual
hibernation cycle in 13-lined ground squirrels by NMR. Physiological
Genomics 31:15-24.
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