Research
Focus
The laboratory conducts research on the resolution of airway epithelial cell hyperplasia
following injury by environmental toxins such as ozone, cigarette smoke, allergens, or by infectious
agents including bacteria and viruses. We apply microarray and proteomic techniques, and immunocytochemical
methods to study the signaling that controls the resolution of hyperplastic airway cells. We have shown
that the persistence of hyperplastic airway cells is caused by dysregulated expression of cell death
regulatory proteins in airway epithelia. Our studies involve analyzing the role of apoptotic genes using
cell culture, organ culture systems and validating our findings in transgenic mice.
Hyperplastic airway cells store and produce mucins; therefore, aberrant resolution leads the persistence
of mucous cells that is associated with chronic bronchitis, cystic fibrosis, asthma, and possibly cancer.
Therefore, we use autopsy and biopsy material from patients with these diseases to investigate the
implications of our findings in clinical settings.
We also investigate the associations of DNA polymorphisms with chronic mucus hypersecretion and chronic
airway obstruction in a cohort of men and women who are current and former smokers. Our initial studies
in the Lovelace Scientific Cohort suggest that the regulation of the Bcl-2 family of proteins is associated
with chronic mucous hypersecretion in population-based studies. Therefore, understanding this pathway
in more detail could provide therapeutic targets to resolve mucous cell metaplasia and the associated
airway obstruction in these chronic diseases. Association of DNA polymorphisms in genes that encode for
other gene families with chronic airway obstruction are also being studied in this cohort of smokers.
We have established that airway epithelial cells, once primed with an injury, have a memory that makes
their response different from cells that were not injured. Therefore, we are in the process of investigating
the molecular mechanisms that allow airway epithelial cells to store such information, because their
inflammatory response is reduced compared to cells that were not primed. These studies may be crucial in
reducing inflammation in response to toxins, bacteria, or allergens.