Areas of Interest
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.
Publications
Selected Publications
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.
 View more publications, see
Pubmed listing.
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