Stephanie Shore

Senior Lecturer on Physiology

Department of Environmental Health

665 Huntington Ave
Building I, Room 307
Boston, MA 02115
Phone: 617.432.0199


Asthma and obesity are both important public health problems, and the prevalence of both conditions is rising. Epidemiological data indicate that obesity increases the risk of developing asthma, but the mechanistic basis for this link remains to be established. We have demonstrated that obese mice have innate airway hyperresponsiveness, a characteristic feature of asthma. Obese mice also have greater responses to ozone or allergen, two common asthma triggers. Using these mice, we are investigating the hypothesis that the hormones and inflammatory cytokines produced in adipose tissue act on the lung to increase its response to asthma triggers. For example, the hormone leptin is produced predominantly in adipocytes, and is involved in the regulation of body weight through effects on eating and energy expenditure. Serum leptin levels are correlated with adiposity and increased by as much as 3-4 fold in obese humans. In addition to its role as a satiety signal, leptin is also pro-inflammatory: leptin receptors belong to the class I family of cytokine receptors and have been demonstrated on a variety of hematopoietic cells, including macrophages and T cells, in which leptin promotes the release of inflammatory cytokines. In contrast, another adipose-derived hormone, adiponectin, is anti-inflammatory, suggesting that declines in this hormone that are observed in the obese may augment the airway inflammation associated with asthma.

We are using knockout mice and antibodies to examine the role of these and a variety of other adipose derived factors in the causing the phenotypic changes observed in the airways of obese mice. Our studies involve measurements of airway hyperresponsiveness (AHR), airway inflammation, and gene expression. We are also examining the effect of exogenous administration of adipocyte-derived factors such as leptin and adiponectin on ozone and allergen induced airway responses. Finally, we are using microarray analysis of genes expressed in the lungs of lean and obese mice to examine how obesity impacts the lung.

One of the characteristics of asthma is an increase in the amount of smooth muscle in the airway wall. We have found that the adipose-derived hormone adiponectin inhibits proliferation of airway smooth muscle cells in culture, and are currently investigating the effects of this adipokine on other smooth muscle cell functions, including contraction and inflammatory gene expression.

In other target cells, adiponectin exerts its effects by activating the enzyme AMP kinase, a cellular regulator of energy status. We are currently investigating the importance of this enzyme for effects of adiponectin on airway smooth muscle. Several anti-diabetic drugs also target this enzyme, and we are investigating their potential therapeutic importance for obesity-related asthma. For these experiments, we use both human and murine airway smooth muscle cells in culture. Standard cell and molecular approaches are being applied to this question, as well as novel tools developed in the MIPS program (magnetic twisting cytometry, force traction microscopy) that allow us to assess force generation in these cells. Additionally, our ability to culture airway smooth muscle from mice allows us to take advantage of genetically modified mice to effect gene deletion.


Ph.D., 1984, McGill University