YuanPu Di - Research

Research Interests

Our laboratory is interested in investigating effects of environmental stress such as toxic chemicals and microorganisms on airway epithelial cell differentiation and lung diseases. One of our current research projects is focused on elucidating the molecular mechanisms that regulate the interaction between airway epithelial cells and exposure to environmental insults such as TCDD and tobacco smoke. We are also interested in how environmental agents affect host defense mechanism, especially airway secretion and infection, that relates to pulmonary disease. The ultimate goal of our laboratory is to develop new potential biomarkers for early detection of pre-neoplastic lesions that is caused by environmental exposure, as well as for the development of novel treatment strategies against toxicant-induced respiratory pathogenesis.

The continuous cell layer of the respiratory epithelium acts as a protective physical barrier against inhaled agents. It also plays a key role in other airway related mechanisms such as inflammatory reactions, immune responses, mucociliary clearance, neurogenic regulation, and anti-infectious secretion. It is known that environmental stress can contribute to various diseases of the respiratory tract, and we are specifically interested in how the respiratory tract copes with these insults. Our laboratory has identified a serous cell type- and airway- specific novel gene, spurt (secretory protein in upper respiratory tracts), through the cDNA microarray system. We have demonstrated in previous studies that this gene responds swiftly and significantly to several environmental stimuli; such as ozone and tobacco smoke exposure. Bioinformatic analyses and characterizing experiments suggest that spurt is a novel secretory protein, and we have observed that spurt is secreted into the human airway lumen. Spurt secretion is increased in sputum from patients with chronic obstructive pulmonary disease (COPD) and asthma, while it is significantly decreased in the sputum of cystic fibrosis (CF) patients. Of potential significance, we have also observed bactericidal activity of spurt's gene product. Because environmental pollution and airway bacterial infection have been associated with various lung diseases, we are particularly interested in understanding the mechanisms of spurt's airway-specific bactericidal activity in the host defense response after environmental insults. Additionally, several other genes that relate to specific Th1/Th2 immune response or innate immunity are also being investigated for their roles in environmental exposure related respiratory diseases.

The research focus of our laboratory is to elucidate the mechanisms of airway pathogenesis due to environmental toxin exposure. In particular, we are trying to explore the genetic variances that contribute to individual susceptibility to lung injury and airway disease. Therefore, our secondary area of research is focused on elucidating the regulatory mechanism and gene expression profiling of toxic exposure- and oxidant-induced respiratory pathogenesis. We are currently using several approaches including transgenic and knockout mouse, microarray, genomics, proteomics, and metabonomics methods to identify a cluster of genes and/or transcriptional factors that could represent the major contributing factors to environmental exposure induced lung diseases.

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Current Research Support

Dates	Position	Title
8/01/09 - 7/31/14	Co-investigator	Caveolin-1: A Novel Modulator of the PP2A/ATM/p53 Pathway
12/01/08 - 11/30/13	Principal Investigator	Epithelial PLUNC as a determinant of Airway Mucosal Antimicrobial Activity
4/01/08 - 3/31/12	Co-investigator	Role of Metalloproteinases in mucin overproduction in COPD
9/28/07 - 9/27/11	Co-investigator	Stem Cells to Enhance Bronchiolar Reparative Capacity
7/01/09 - 6/30/11	Principal Investigator	ARRA Supplement NIH/NHLBI Epithelial PLUNC as a determinant of Airway Mucosal Antimicrobial Activity
12/01/08 - 11/30/10	Principal Investigator	Antimicrobial and Anti-inflammatory Functions of PLUNC in Periodontal Diseases

 

Completed Research Support - last 5 years

Dates	Position	Title
9/01/02 - 8/31/05	Principal Investigator	Effects of Tobacco Smoke Exposure on Airway Bactericidal Activity
7/01/03 - 6/30/05	Principal Investigator	American Heart Association (AHA), Pennsylvania Delaware Affiliate, Functional role of a novel BPI-like/spurt gene family in airway innate immunity
8/01/07 - 7/31/09	Principal Investigator	CFF/Pittsburgh CF Center Maintenance of Lung Epithelial Stem Cells from Normal and CF Human Airway
6/06/05 - 3/31/10	Co-Investigator	Particulate Matter/Mycoplasma Stress Interactions