Yin Chen
Assistant Professor, BIO5 Institute
Associate Professor, Pharmacology and Toxicology
Primary Department
(520) 626-4715
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.


Chen, Y., Zhao, Y. H., Di, Y. -., & Wu, R. (2001). Characterization of human mucin 5B gene expression in airway epithelium and the genomic clone of the amino-terminal and 5′-flanking region. American Journal of Respiratory Cell and Molecular Biology, 25(5), 542-553.

PMID: 11713095;Abstract:

Human mucin (MUC) 5B gene expression in human airway epithelium was studied in both tissue sections and cultures of tracheobronchial epithelial (TBE) cells. In situ hybridization demonstrated that MUC5B message was expressed mainly in the mucous cells of submucosal glands of normal human airway tissues. Nevertheless, an elevated MUC5B message level could be seen in surface goblet cells from patients with airway diseases and inflammation. Regardless of the airway tissue sources, MUC5B message was regulated by all-trans-retinoic acid (RA) and culture conditions in both primary and passage-1 cultures of TBE cells. MUC5B message, to a lesser extent, was also found in the immortalized epithelial cell line HBE1, but not in BEAS-2B cells. To elucidate the molecular mechanism of MUC5B gene expression, a genomic clone was obtained and sequenced for the amino terminal and the 5′-flanking region of MUC5B gene. A luciferase reporter construct containing 4,169 base pairs of the 5′-flanking region of MUC5B gene demonstrated a cell type-specific basal promoter activity in transfection studies. Both RA and the air-liquid interface culture condition further enhanced this promoter activity. These results suggest that the 5′-flanking region of MUC5B gene contains cis-elements that are potentially involved in the regulation of MUC5B gene expression.

Chen, Y., Vasquez, M. M., Zhu, L., Lizarraga, R. E., Krutzsch, M., Einspahr, J., Alberts, D. S., Di, P. Y., Martinez, F. D., & Guerra, S. (2017). Effects of Retinoids on Augmentation of Club Cell Secretory Protein. American journal of respiratory and critical care medicine.
BIO5 Collaborators
Yin Chen, Stefano Guerra
Velichko, S., Zhou, X., Zhu, L., Anderson, J. D., Wu, R., & Chen, Y. (2016). A Novel Nuclear Function for the Interleukin-17 Signaling Adaptor Protein Act1. PloS one, 11(10), e0163323.

In the context of the human airway, interleukin-17A (IL-17A) signaling is associated with severe inflammation, as well as protection against pathogenic infection, particularly at mucosal surfaces such as the airway. The intracellular molecule Act1 has been demonstrated to be an essential mediator of IL-17A signaling. In the cytoplasm, it serves as an adaptor protein, binding to both the intracellular domain of the IL-17 receptor as well as members of the canonical nuclear factor kappa B (NF-κB) pathway. It also has enzymatic activity, and serves as an E3 ubiquitin ligase. In the context of airway epithelial cells, we demonstrate for the first time that Act1 is also present in the nucleus, especially after IL-17A stimulation. Ectopic Act1 expression can also increase the nuclear localization of Act1. Act1 can up-regulate the expression and promoter activity of a subset of IL-17A target genes in the absence of IL-17A signaling in a manner that is dependent on its N- and C-terminal domains, but is NF-κB independent. Finally, we show that nuclear Act1 can bind to both distal and proximal promoter regions of DEFB4, one of the IL-17A responsive genes. This transcriptional regulatory activity represents a novel function for Act1. Taken together, this is the first report to describe a non-adaptor function of Act1 by directly binding to the promoter region of IL-17A responsive genes and directly regulate their transcription.

Chen, Y., Zhao, Y. H., & Wu, R. (2001). Differential regulation of airway mucin gene expression and mucin secretion by extracellular nucleotide triphosphates. American Journal of Respiratory Cell and Molecular Biology, 25(4), 409-417.

PMID: 11694445;Abstract:

The effects of extracellular nucleotide triphosphates on the stimulation of mucin production by airway epithelial cells were examined. The order of potency in stimulating mucin secretion in primary cultures of human tracheobronchial epithelial cells is: uridine 5′-triphosphate (UTP) ≈ adenosine 5′-triphosphate (ATP) ≈ ATP-γ-S > uridine 5′-diphosphate ≈ adenosine 5′-diphosphate > α,β-methylene ATP >> adenosine. However, only UTP can increase mucin gene (MUC5AC, MUC5B) expression; ATP and other analogues have no stimulatory effect. The stimulation of MUC5AC and MUC5B expression by UTP is time- and dose-dependent. A similar effect on the elevation of mucous cell population in mouse airway epithelium can be demonstrated in vivo by an intratracheal instillation of UTP-saline solution. The stimulatory effect of UTP or ATP on mucin secretion was inhibited by pertussis toxin, U73122, and Calphostin C, but not by PD98059, suggesting a G-protein/phospholipase (PL) C/protein kinase (PK) C-dependent and mitogen-activated protein kinase (MAPK)-independent signaling pathway. However, the stimulatory effect of UTP on mucin gene expression was sensitive to pertussis toxin and PD98059, but not to Calphostin C and U73122, suggesting a G-protein/MAPK-dependent and PLC/PKC-independent signaling pathway. These findings are the first demonstration that UTP, a pyrimidine nucleotide triphosphate, can enhance both mucin secretion and mucin gene expression through different signaling pathways.

Lee, W., Chen, Y., Wang, W., & Mosser, A. (2015). Growth of human rhinovirus in H1-HeLa cell suspension culture and purification of virions. Methods in molecular biology (Clifton, N.J.), 1221, 49-61.

HeLa cell culture is the most widely used system for in vitro studies of the basic biology of human rhinovirus (HRV). It is also useful for making sufficient quantities of virus for experiments that require highly concentrated and purified virus. This chapter describes the protocols for producing a large amount of HeLa cells in suspension culture, using these cells to grow a large quantity of virus of HeLa-adapted HRV-A and -B serotypes, and making highly concentrated virus stock and highly purified virions. These purified HRV virions are free of cellular components and suitable for experiments that are sensitive to cellular contaminations.