Yin Chen

Yin Chen

Assistant Professor, BIO5 Institute
Member of the Graduate Faculty
Professor, Pharmacology and Toxicology
Primary Department
(520) 626-4715

Research Interest

Research Interest
Yin Chen, PhD. is an Assistant Professor in Pharmacology and Toxicology in the College of Pharmacy at UA. Dr. Chen’s research focus is on epithelial biology. He was a research faculty in University of California, Davis and an Assistant Investigator in Chemical Industry Institute of Toxicology (former CIIT and later Hamner Institute). His long-term research objective is to understand the dysfunction of airway epithelial mucosa in the pathogenesis of a variety of acute and chronic airway diseases. His current research programs are: a) understanding the molecular mechanisms underlying airway mucous cell development and mucous cell metaplasia in chronic diseases including cancer, COPD and asthma; (b) understanding the function and regulation of novel COPD associated genes and developing novel compounds to treat COPD; (c) understanding the impact of fungal exposure on airway innate immunity and its contribution to the development and exacerbation of asthma. Dr. Chen has more than 30 publications including peer-reviewed research articles, reviews and book chapters. He has served as the PI on one R01, two R21, one Flight Attendant Medical Institute (FAMRI) Innovative Clinical Award and one Arizona Biomedical Research Commission Award. He has also served as co-PI on two R01 and one P01 grants. He has built a long productive track record in studying airway mucus production and respiratory viral infection using primary airway epithelial cell model. He routinely cultivate and use primary epithelial cells from eye, salivary gland, airway surface and submucosal gland in different species (e.g. human, monkey, pig, rat and mouse) as our in vitro model to study mucin genes. The differentiated primary culture model demonstrates pseudostratified morphology, is composed of ciliated, non-ciliated, and goblet cells, and has a transepithelial barrier with high electro-resistance. He has also established in vivo exposure system to study the pulmonary effect of the exposure to particulates, pathogens and gases. Using this system, he has developed various airway disease models including CS-induced COPD model, ovalbumin-induced asthma model, fungal-induced asthma model and several infection models such as H1N1, rhinovirus, Aspergillus, and Alternaria.


Zhu, L., Di, P. Y., Wu, R., Pinkerton, K. E., & Chen, Y. (2015). Repression of CC16 by cigarette smoke (CS) exposure. PloS one, 10(1), e0116159.

Club (Clara) Cell Secretory Protein (CCSP, or CC16) is produced mainly by non-ciliated airway epithelial cells including bronchiolar club cells and the change of its expression has been shown to associate with the progress and severity of Chronic Obstructive Pulmonary Disease (COPD). In an animal model, the lack of CC16 renders the animal susceptible to the tumorigenic effect of a major CS carcinogen. A recent population-based Tucson Epidemiological Study of Airway Obstructive Diseases (TESAOD) has indicated that the low serum CC16 concentration is closely linked with the smoke-related mortality, particularly that driven by the lung cancer. However, the study of CC16 expression in well-defined smoke exposure models has been lacking, and there is no experimental support for the potential causal link between CC16 and CS-induced pathophysiological changes in the lung. In the present study, we have found that airway CC16 expression was significantly repressed in COPD patients, in monkey CS exposure model, and in CS-induced mouse model of COPD. Additionally, the lack of CC16 exacerbated airway inflammation and alveolar loss in the mouse model. Therefore, CC16 may play an important protective role in CS-related diseases.

Chen, Y., Thai, P., Zhao, Y., Ho, Y., DeSouza, M. M., & Reen, W. u. (2003). Stimulation of airway mucin gene expression by interleukin (IL)-17 through IL-6 paracrine/autocrine loop. Journal of Biological Chemistry, 278(19), 17036-17043.

PMID: 12624114;Abstract:

Mucus hypersecretion and persistent airway inflammation are common features of various airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. One key question is: does the associated airway inflammation in these diseases affect mucus production? If so, what is the underlying mechanism? It appears that increased mucus secretion results from increased mucin gene expression and is also frequently accompanied by an increased number of mucous cells (goblet cell hyperplasia/metaplasia) in the airway epithelium. Many studies on mucin gene expression have been directed toward Th2 cytokines such as interleukin (IL)-4, IL-9, and IL-13 because of their known pathophysiological role in allergic airway diseases such as asthma. However, the effect of these cytokines has not been definitely linked to their direct interaction with airway epithelial cells. In our study, we treated highly differentiated cultures of primary human tracheobronchial epithelial (TBE) cells with a panel of cytokines (interleukin-1α, 1β, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, and tumor necrosis factor α). We found that IL-6 and IL-17 could stimulate the mucin genes, MUC5B and MUC5AC. The Th2 cytokines IL-4, IL-9, and IL-13 did not stimulate MUC5AC or MUC5B in our experiments. A similar stimulation of MUC5B/Muc5b expression by IL-6 and IL-17 was demonstrated in primary monkey and mouse TBE cells. Further investigation of MUC5B expression demonstrated that IL-17's effect is at least partly mediated through IL-6 by a JAK2-dependent autocrine/paracrine loop. Finally, evidence is presented to show that both IL-6 and IL-17 mediate MUC5B expression through the ERK signaling pathway.

Chen, Y., Hamati, E., Lee, P., Lee, W., Wachi, S., Schnurr, D., Yagi, S., Dolganov, G., Boushey, H., Avila, P., & Reen, W. u. (2006). Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways. American Journal of Respiratory Cell and Molecular Biology, 34(2), 192-203.

PMID: 16210696;PMCID: PMC2644182;Abstract:

Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression. In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis. At 24 h after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions. Indeed, a significant stimulation of IFN-β secretion was detected after RV16 infection. Neutralizing antibody specific to IFN-β and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA-dependent protein kinase, could block both IFN-β production and RV-induced gene expression. Thus, IFN-β-dependent pathway is a part of the double-stranded RNA-initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.

Y., D., Reen, W. u., Chen, Y., Tarasova, N., & Chang, M. M. (2007). PMA stimulates MUC5B gene expression through an Sp1-based mechanism in airway epithelial cells. American Journal of Respiratory Cell and Molecular Biology, 37(5), 589-597.

PMID: 17600309;PMCID: PMC2048678;Abstract:

We previously showed that the MUC5B gene expression was elevated by phorbol 12-myristate 13-acetate (PMA) through an epidermal growth factor receptor-independent Ras/MEKK1/JNK and P38 signaling-based transcriptional mechanism. In the current study, we elucidated the molecular basis of this transcriptional regulation using promoter-reporter gene expression and chromatin immunoprecipitation (ChIP) assays with primary human bronchial epithelial cells that are cultured at the air-liquid interface. We have observed that PMA-induced MUC5B promoter activity is blocked by the Sp1-binding inhibitor, mithramycin A, in a dose-dependent manner. Deletion analysis with the MUC5B promoter construct demonstrated that both basal and PMA-induced promoter-reporter activities reside within the -222/-78 bp region relative to the transcriptional start site. NoShift transcriptional factor assays demonstrated that PMA stimulated Sp1 binding, but not STAT1 and c-Myc binding. Immunoprecipitation studies also verified the enhanced phosphorylation of Sp1 after PMA treatment. Site-directed mutagenesis and transfection studies demonstrated the involvement of Sp1-1 (-122/-114) and the Sp1-2 (-197/-186) cis elements in the basal and PMA-induced MUC5B promoter activity. The ChIP assay with anti-RNA polymerase II reconfirmed the PMA-induced MUC5B promoter activity by showing enhanced RNA polymerase II-DNA complex containing putative MUC5B Sp1-1, Sp1-2, or Sp1-3 sites. However, the ChIP assay using anti-Sp1 antibody demonstrated that the PMA-stimulated binding is only at Sp1-2. These results suggested an Sp1-based transcriptional mechanism with Sp1-1 as the regulator of basal MUC5B promoter activity and Sp1-2 as the regulator of PMA-induced MUC5B gene expression in the human airway epithelial cells.

Chen, Y., Zhao, Y. H., Kalaslavadi, T. B., Hamati, E., Nehrke, K., Le, A. D., Ann, D. K., & Reen, W. u. (2004). Genome-Wide Search and Identification of a Novel Gel-Forming Mucin MUC19/Muc19 in Glandular Tissues. American Journal of Respiratory Cell and Molecular Biology, 30(2), 155-165.

PMID: 12882755;Abstract:

Gel-forming mucins are major contributors to the viscoelastic properties of mucus secretion. Currently, four gel-forming mucin genes have been identified: MUC2, MUC5AC, MUCSB, and MUC6. All these genes have five major cysteine-rich domains (four von Willebrand factor [vWF] C or D domains and one Cystine-knot [CT] domain) as their distinctive features, in contrast to other non-gel-forming type of mucins. The CT domain is believed to be involved in the initial mucin dimer formation and have very succinct relationship between different gel-forming mucins across different species. Because of gene duplication and evolutional modification, it is very likely that other gel-forming mucin genes exist. To search for new gel-forming mucin candidate genes, a "Hidden Markov Model"(HMM) was built from the common features of the CT domains of those gel-forming mucins. By using this model to screen all protein databases as well as the six-frame translated expression sequence tag and translated human genomic databases, we identified a locus located at the peri-centromere region of human chromosome 12 and the corresponding homologous region of mouse chromosome 15. We cloned the 3′ end of this gene and its mouse homolog. We found one vWF C domain, one CT domain, and various mucin-like threonine/serine-rich repeats. Phylogenetic analysis indicated the close relationship between this gene and the submaxillary mucin from porcine and bovine. A polydispersed signal was observed on the Northern blot, which indicates very large mRNA size. Further analysis of the upstream genomic sequences generated from human and mouse genome projects revealed three additional vWF D domains and many mucin-like threonine/serine- rich repeats. The expression of this gene is restricted to the mucous cells of various glandular tissues, including sublingual gland, submandibular gland, and submucosal gland of the trachea. Based on the chronological convention, we have given the name MUC19 to the human ortholog and Muc19 to the mouse.