Bio

Bio


Dr. Yu's research centers on the role of mast cell-related mechanisms in health and diseases.

Education & Certifications


  • MD, Liaoning Chinese Medical College, Shenyang, China, Medicine (1991)
  • MS, Dalian Medical College, Dalian, China, Microbiology (1994)
  • PhD, University of California, Davis, Immunology (2001)
  • Board Certificate, California Board of Acupuncture, Licensed Practitioner of Chinese Medicine (Acupuncture and Herbal Medicine) (2012)

Patents


  • Mang Yu. "China P.Rep.Submerged fermentation of Cordyceps sinensis", China Patent Administration, Mar 14, 2001

Publications

All Publications


  • Thirdhand smoke component can exacerbate a mouse asthma model through mast cells. The Journal of allergy and clinical immunology Yu, M., Mukai, K., Tsai, M., Galli, S. J. 2018

    Abstract

    Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for asthma or asthma exacerbation if the disease is already present, how exposure to THS can influence the development or exacerbation of asthma remains unknown.We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a mouse model elicited by means of repeated intranasal challenge with cockroach antigen (CRA).Wild-type mice, α7 nicotinic acetylcholine receptor (nAChR)- or mast cell (MC)-deficient mice, and mice with MCs that lacked α7 nAChRs or were the host's sole source of α7 nAChRs were subjected to epicutaneous NNK exposure, intranasal CRA challenge, or both, and the severity of features of asthma pathology, including airway hyperreactivity, airway inflammation, and airway remodeling, was assessed.We found that α7 nAChRs were required to observe adverse effects of epicutaneous NNK exposure on multiple features of CRA-induced asthma pathology. Moreover, MC expression of α7 nAChRs contributed significantly to the ability of epicutaneous NNK exposure to exacerbate airway hyperreactivity to methacholine, airway inflammation, and airway remodeling in this model.Our results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a CRA-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.

    View details for PubMedID 29678746

  • A TNFRSF14-Fc epsilon RI-mast cell pathway contributes to development of multiple features of asthma pathology in mice NATURE COMMUNICATIONS Sibilano, R., Gaudenzio, N., DeGorter, M. K., Reber, L. L., Hernandez, J. D., Starkl, P. M., Zurek, O. W., Tsai, M., Zahner, S., Montgomery, S. B., Roers, A., Kronenberg, M., Yu, M., Galli, S. J. 2016; 7

    Abstract

    Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production. In mouse models of asthma, TNFRSF14 blockade with a neutralizing antibody administered after antigen sensitization, or genetic deletion of Tnfrsf14, diminishes plasma levels of antigen-specific IgG1 and IgE antibodies, airway hyperreactivity, airway inflammation and airway remodelling. Finally, by analysing two types of genetically MC-deficient mice after engrafting MCs that either do or do not express TNFRSF14, we show that TNFRSF14 expression on MCs significantly contributes to the development of multiple features of asthma pathology.

    View details for DOI 10.1038/ncomms13696

    View details for Web of Science ID 000389853400001

    View details for PubMedID 27982078

    View details for PubMedCentralID PMC5171877

  • Identification of an IFN-gamma/mast cell axis in a mouse model of chronic asthma JOURNAL OF CLINICAL INVESTIGATION Yu, M., Eckart, M. R., Morgan, A. A., Mukai, K., Butte, A. J., Tsai, M., Galli, S. J. 2011; 121 (8): 3133-3143

    Abstract

    Asthma is considered a Th2 cell–associated disorder. Despite this, both the Th1 cell–associated cytokine IFN-γ and airway neutrophilia have been implicated in severe asthma. To investigate the relative contributions of different immune system components to the pathogenesis of asthma, we previously developed a model that exhibits several features of severe asthma in humans, including airway neutrophilia and increased lung IFN-γ. In the present studies, we tested the hypothesis that IFN-γ regulates mast cell function in our model of chronic asthma. Engraftment of mast cell–deficient KitW(-sh/W-sh) mice, which develop markedly attenuated features of disease, with wild-type mast cells restored disease pathology in this model of chronic asthma. However, disease pathology was not fully restored by engraftment with either IFN-γ receptor 1–null (Ifngr1–/–) or Fcε receptor 1γ–null (Fcer1g–/–) mast cells. Additional analysis, including gene array studies, showed that mast cell expression of IFN-γR contributed to the development of many FcεRIγ-dependent and some FcεRIγ-independent features of disease in our model, including airway hyperresponsiveness, neutrophilic and eosinophilic inflammation, airway remodeling, and lung expression of several cytokines, chemokines, and markers of an alternatively activated macrophage response. These findings identify a previously unsuspected IFN-γ/mast cell axis in the pathology of chronic allergic inflammation of the airways in mice.

    View details for DOI 10.1172/JCI43598

    View details for Web of Science ID 000293495500024

    View details for PubMedID 21737883

    View details for PubMedCentralID PMC3148724

  • Perinatal environmental tobacco smoke exposure alters the immune response and airway innervation in infant primates JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Yu, M., Zheng, X., Peake, J., Joad, J. P., Pinkerton, K. E. 2008; 122 (3): 640-647

    Abstract

    Epidemiologic studies associate environmental tobacco smoke (ETS) exposure with childhood asthma.To investigate whether specific pathophysiological alterations that contribute to asthma development in human beings can be induced in infant monkeys after perinatal ETS exposure.Rhesus macaque fetuses/infants were exposed to ETS at 1 mg/m(3) of total suspended particulate matter from 50 days gestational age to 2.5 months postnatal age. Inflammatory and neural responses to ETS exposure were measured in the infant monkeys.Perinatal ETS exposure could induce systemic and local responses, which include significant elevation of plasma levels of C5a and brain-derived neurotrophic factor, as well as significant increases in pulmonary expression of proinflammatory cytokine TNF-alpha and T(H)2 cytokine IL-5, chemokine monocyte chemoattractant protein 1, and the density of substance P-positive nerves along the bronchial epithelium. Perinatal ETS exposure also significantly increased the numbers of mast cells, eosinophils, monocytes, and lymphocytes in the lungs of infant monkeys. In addition, ex vivo measurements showed significantly increased levels of IL-4 and brain-derived neurotrophic factor in the culture supernatant of PBMCs. Interestingly, as an important component of cigarette smoke, LPS was detected in the plasma of infant monkeys subjected to perinatal exposure to ETS. In contrast, an inhibitory effect of perinatal ETS exposure was also observed, which is associated with decreased phagocytic activity of alveolar macrophages and a significantly decreased level of nerve growth factor in the bronchoalveolar lavage fluid.Perinatal ETS exposure can induce a T(H)2-biased inflammatory response and alter airway innervation in infant monkeys.

    View details for DOI 10.1016/j.jaci.2008.04.038

    View details for Web of Science ID 000259234000030

    View details for PubMedID 18571708

  • Mast cells can promote the development of multiple features of chronic asthma in mice JOURNAL OF CLINICAL INVESTIGATION Yu, M., Tsai, M., Tam, S., Jones, C., Zehnder, J., Galli, S. J. 2006; 116 (6): 1633-1641

    Abstract

    Bronchial asthma, the most prevalent cause of significant respiratory morbidity in the developed world, typically is a chronic disorder associated with long-term changes in the airways. We developed a mouse model of chronic asthma that results in markedly increased numbers of airway mast cells, enhanced airway responses to methacholine or antigen, chronic inflammation including infiltration with eosinophils and lymphocytes, airway epithelial goblet cell hyperplasia, enhanced expression of the mucin genes Muc5ac and Muc5b, and increased levels of lung collagen. Using mast cell-deficient (Kit(W-sh/W-sh) and/or Kit(W/W-v)) mice engrafted with FcRgamma+/+ or FcRgamma-/- mast cells, we found that mast cells were required for the full development of each of these features of the model. However, some features also were expressed, although usually at less than wild-type levels, in mice whose mast cells lacked FcRgamma and therefore could not be activated by either antigen- and IgE-dependent aggregation of Fc epsilonRI or the binding of antigen-IgG1 immune complexes to Fc gammaRIII. These findings demonstrate that mast cells can contribute to the development of multiple features of chronic asthma in mice and identify both Fc Rgamma-dependent and Fc Rgamma-independent pathways of mast cell activation as important for the expression of key features of this asthma model.

    View details for DOI 10.1172/JCI25702

    View details for Web of Science ID 000237979700025

    View details for PubMedID 16710480

    View details for PubMedCentralID PMC1462940

  • The role of interleukin-6 in pulmonary inflammation and injury induced by exposure to environmental air pollutants TOXICOLOGICAL SCIENCES Yu, M., Zheng, X., Witschi, H., Pinkerton, K. E. 2002; 68 (2): 488-497

    Abstract

    This study was designed to examine the role of the cytokine interleukin-6 (IL-6) in environmental air pollutant-induced pulmonary inflammation, injury, and repair. IL-6 knockout (KO) mice and wild-type (WT) mice were exposed to filtered air; aged and diluted cigarette smoke (ADSS), a surrogate for environmental tobacco smoke; ozone; or ADSS followed by ozone (ADSS/ozone). The proportion of monocytes and neutrophils recovered by bronchoalveolar lavage (BAL) as well as the level of total protein in BAL fluid were significantly increased in both IL-6 KO and WT mice following exposure to ozone or to ADSS/ozone. However, bromodeoxyuridine (BrdU) labeling within terminal bronchiolar epithelium and proximal alveolar regions in IL-6 KO mice exposed to ozone or to ADSS/ozone was significantly reduced compared with IL-6 sufficient mice (WT). WT mice treated with IL-6 antibodies also demonstrated a reduction in BrdU cell labeling similar to that observed in IL-6 KO mice following exposure to ozone or ADSS/ozone. Clara cell secretory protein (CCSP) abundance, a marker of Clara cell maturation and function, was markedly reduced in the terminal bronchiolar epithelium of WT mice following exposure to ADSS and/or ozone, whereas CCSP abundance was unchanged in IL-6 KO mice. We conclude that endogenous IL-6 in mice plays a critical role in the progress of lung inflammation/injury, but CCSP may also play a role to protect the lungs of mice exposed to toxic air pollutants. Data from this study further suggest that IL-6 antibody treatment modalities may be a means to attenuate pulmonary inflammation and injury.

    View details for Web of Science ID 000177226000028

    View details for PubMedID 12151646

  • Short-term exposure to aged and diluted sidestream cigarette smoke enhances ozone-induced lung injury in B6C3F1 mice TOXICOLOGICAL SCIENCES Yu, M., Pinkerton, K. E., Witschi, H. 2002; 65 (1): 99-106

    Abstract

    To determine the effects of aged and diluted sidestream cigarette smoke (ADSS) as a surrogate of environmental tobacco smoke (ETS) on ozone-induced lung injury, male B6C3F1 mice were exposed to (1) filtered air (FA), (2) ADSS, (3) ozone, or (4) ADSS followed by ozone (ADSS/ozone). Exposure to ADSS at 30 mg/m3 of total suspended particulates (TSP) for 6 h/day for 3 days, followed by exposure to ozone at 0.5 ppm for 24 h was associated with a significant increase in the number of cells recovered by bronchoalveolar lavage (BAL) compared with exposure to ADSS alone or ozone alone. The proportion of neutrophils and lymphocytes, as well as total protein level in BAL, was also significantly elevated following ADSS/ozone exposure, when compared with all other groups. Within the centriacinar regions of the lungs, the percentage of proliferating cells identified by bromodeoxyuridine (BrdU) labeling was unchanged from control, following exposure to ADSS alone, but was significantly elevated following exposure to ozone (280% of control) and further augmented in a statistically significant manner in mice exposed to ADSS/ozone (402% of control). Following exposure to ozone or ADSS/ozone, the ability of alveolar macrophages (AM) to release interleukin (IL)-6 under lipopolysaccharide (LPS) stimulation was significantly decreased, while exposure to ADSS or ADSS/ozone caused a significantly increased release of tumor necrosis factor alpha from AM under LPS stimulation. We conclude that ADSS exposure enhances the sensitivity of animals to ozone-induced lung injury.

    View details for Web of Science ID 000173097400012

    View details for PubMedID 11752689

  • The effects of phenethyl isothiocyanate, N-acetylcysteine and green tea on tobacco smoke-induced lung tumors in strain A/J mice CARCINOGENESIS Witschi, H., Espiritu, I., Yu, M., Willits, N. H. 1998; 19 (10): 1789-1794

    Abstract

    Male and female strain A/J mice were exposed to a mixture of cigarette sidestream and mainstream smoke at a chamber concentration of total suspended particulates of 82.5 mg/m3. Exposure time was 6 h/day, 5 days/week for 5 months. The animals were allowed to recover for another 4 months in filtered air before sacrifice and lung tumor count. Male animals were fed either 0.2% N-acetylcysteine (NAC) or 0.05% phenethyl isothiocyanate (PEITC) in diet AIN-76A with 5% corn oil added. Female animals received normal laboratory chow and were given a 1.25% extract of green tea in the drinking water. Corresponding control groups were fed diets without NAC or PEITC or given plain tap water. Exposure to tobacco smoke increased lung tumor multiplicity to 1.1-1.6 tumors/lung, significantly higher than control values (0.5-1.0 tumors/lung). None of the putative chemopreventive agents (NAC, PEITC or green tea extract) had a protective effect. In positive control experiments, PEITC significantly reduced both lung tumor multiplicity and incidence in mice treated with the tobacco smoke-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In mice treated with three different doses of urethan and fed NAC in the diet, a significant reduction in lung tumor multiplicity was found only at one dose level. Green tea extract did not reduce lung tumor multiplicity in animals treated with a single dose of NNK. It was concluded that successful chemoprevention of tobacco smoke-induced lung tumorigenesis might require administration of several chemopreventive agents rather than just a single one.

    View details for Web of Science ID 000076511800012

    View details for PubMedID 9806160