Why I
Joined GGCP

Having an understanding of pathology across a wide range of animal species and the ability to interpret and translate the importance of pathologic findings across species are invaluable assets in scientific research. It is because of this comparative emphasis that I joined the Graduate Group in Comparative Pathology (GGCP). GGCP offers a unique training program utilizing a broad-based curriculum that emphasizes both human and veterinary aspects of pathology, thus allowing students to understand the mechanisms of disease in a number of different species. Students in the GGCP program also learn the importance of experimental design, analytical thought, and scientific writing. GGCP offers students the opportunity to interact and collaborate with a first-class faculty group, highly esteemed and productive in their respective fields and representing a wide array of research interests. Because of the diversity of the faculty and graduate group, students from many backgrounds are able to develop a rewarding research program tailored to their specific interests.

Childhood asthma (allergic airway disease) is an increasing problem in the United States, especially within inner-city areas. Children are a unique population with respect to diseases of the airways as airway development and growth continue well into adolescence and young adulthood. Because of this, there is great concern that childhood asthma may detrimentally affect airway development and growth and potentially affect long-term lung function.

The lesions of allergic airway disease (i.e., airway remodeling) are well defined, but their development is complex and not completely understood, especially during airway development. One factor that is thought to play a critical role in development of remodeling lesions is transforming growth factor beta (TGF-beta). TGF-beta is a multifunctional cytokine that regulates a wide array of normal physiologic events, including cellular differentiation, growth and apoptosis, immune cell function, extracellular matrix deposition, and fibroblast activation and migration. TGF-beta also plays a critical role in wound healing. These activities are regulated through a group of intracellular molecules known as Smads that, once activated by TGF-beta, act as nuclear transcription factors.

For our research we utilize a nonhuman primate (Rhesus monkey) model of allergic airway disease in which we are able to recreate allergic airway disease at various stages of postnatal airway development. My research specifically is aimed at discovering which aspects of the TGF-beta/Smad signaling pathways are altered and in what manner in the development of airway remodeling associated with allergic airway disease and at evaluating these changes at various stages of postnatal development.

Another key aim is to determine how concurrent exposure to a common oxidant air pollutant, ozone, further affects TGF-beta/Smad signaling and airway remodeling associated with allergic airway disease.

Figure 1. Trachea, rhesus macaque. Allergen-treated airways (right) show increased TGF-beta immunoreactivity compared to filtered air treated airways (left). TGF-beta immunoreactivity is primarily associated with basal cells, fibroblasts, and inflammatory cells in allergen-treated airways, unlike filtered-air-treated airways in which immunoreactivity is mainly isolated to respiratory epithelium and basal cells.

Figure 2. Trachea, rhesus macaque. Nuclear localization of Smad 2/3 is increased in allergen-treated airways (right) as compared to filtered-air-treated airways (left). Nuclear localization occurs primarily within basal cells and fibroblasts.