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.

CONTACT INFORMATION

Fax: Phone: (505) 348-9495
Fax: (505) 348-8567
Email: ytesfaig@LRRI.org

Lovelace Respiratory Research Institute
2425 Ridgecrest Dr., SE
Albuquerque, NM 87108

Affiliations

• University of New Mexico School of Medicine, Professor, Department of Biochemistry and Molecular Biology
• American Thoracic Society
• American Society of Biochemistry and Molecular Biology
• American Association for Cancer Research (AACR, USA)

Current Projects in the Lab

• Identification of the cell types that are removed during the recovery process from inflammation-induced injury of the airway epithelium
  — organ cultures from microdissected nasal and bronchial tissues
  — primary airway cultures
• Identification of Bcl-2 family of proteins essential for the resolution of epithelial cell hyperplasias
• Expression of Bcl-2 family of proteins in airway epithelia of patients with chronic lung diseases, such as chronic bronchitis, cystic fibrosis, and asthma
• Regulation of Bcl-2 expression by its promoter activity and mRNA stability
• Identification of single nucleotide polymorphisms and mutations in genes that encode for proteins regulating expression of Bcl-2 family members and their association with chronic mucus hypersecretion and chronic airway obsturction
• Investigating the association of single nucleotide polymorphisms in gene families with chronic airway obstruction