The overall goal of our research is to gain insight into the pathogenic mechanisms involved in asthma and chronic bronchitis. An ovalbumin-induced mouse model of asthma, which closely resembles the development of lung injury in humans is used. Cell-to-cell interactions (cytokines), immune regulation, pulmonary physiology, and collagen metabolism represent areas of concentration. Also, clinical studies in patients involving risk factors associated with asthma as well as new possible therapeutic interventions are currently being investigated.

The pathogenic mechanisms involved in the development of asthma are obscure and complex. The pathologic features of the lesion include an allergic inflammatory process and collagen deposition (scar formation). In the healing process there must be an optimal balance between scar formation and regeneration of normal architecture. Unfortunately, in many pulmonary and non-pulmonary disease states this is not the case; abnormal and pathologic amounts of collagen are commonly deposited. The mechanism for this increased collagen synthesis is not understood and may have significant clinical ramifications.

Lab Rotation Projects:
Asthma is the most common chronic disease in developed countries. In the U.S. asthma has increased over the past two decades with young children having the highest rate of hospitalization for this disorder. The incidence and severity of disease has increased dramatically in the past several years. Most studies investigating the pathogenesis of asthma have focused on the acute inflammatory aspects of the disease, with little attention given to the mechanisms involved in the long-term chronic processes that may regulate outcome to recurrent disease or the establishment of tolerance. In our ovalbumin-induced murine model of allergic airway disease, there is a natural progression from acute disease at 3-14 days of aerosol antigen exposure to the development of tolerance after 6 weeks of aerosol antigen exposure. The focus of our laboratory is to investigate the role of regulatory T cells in the induction of tolerance in this model. In addition, we hypothesize that these regulatory T cells interact with an atypical “non-professional” antigen presenting cell possibly B-cells or lung epithelial cells. Rotations in our laboratory will involve studying functional aspects of both regulatory T cells and “non-professional” antigen presenting cells as they pertain to the development of tolerance in this murine model allergic airway disease.

Schramm CM, Puddington L, Wu C, Guernsey L, Thrall RS (2004). Discontinuous inhalation of antigen re-establishes acute allergic airway disease in non-responsive animals continuously exposed to antigen. Am J Pathol 164:295-304.

Cloutier MM, Guernsey L, Wu CA, Thrall RS (2004). Airway epithelium in a murine model of allergic airway disease. Am J Pathol (In Press).

Morris JB, Symanowicz PT, Olsen JE, Thrall RS, Cloutier MM, Hubbard AK (2003). Immediate sensory-nerve mediated respiratory responses to inspired acrolein and acetic acid vapors in healthy and allergic airway diseased mice. J Appl Physiol 94: 1563-1571.

Hubbard AK, Symanowicz P, Thibodeau M, Thrall RS, Schramm CM, Cloutier MM, and Morris JB (2002). Effect of nitrogen dioxide in ovalbumin-induced allergic airway disease in a murine model. J Tox Environ Hlth 65:101-107.

Wu CA, Puddington L, Whiteley HE, Yiamouyiannis CA, Schramm CM, Muhammadu F, Thrall RS (2001). Murine cytomegalovirus infection alters TH1/Th2 cytokine expression, decreases pulmonary eosinophilia, and enhances mucus production in allergic airway disease. J Immunol 167:2798-2807.

Schramm CM, Puddington L, Yiamouyiannis CA, Lingenheld EG, Whiteley HE, Noonan TC, Thrall RS (2000). Synergistic proinflammatory roles of TCRgd and TCRab lymphocytes in a murine model of asthma. Am J Resp Cell Mol Biol 22:218-225.

Tandon R, Sha’afi RI, Thrall RS (2000). Neutrophil B2 integrin upregulation in blocked by a p38 MAP kinase inhibitor. Biochem Biophy Res Comm 270:858-862.