My research focus is to study the mechanisms underlying cockroach exposure and how it induces allergic sensitization and asthma. We are identifying genes involved in specific immune responsiveness to cockroach allergen by integrating genetic and genomic approaches. Also, we are studying the role of the cockroach allergen-CD206 axis in innate immune responses and genetic regulation by an integrated approach that incorporates functional studies, gene knockout mouse models, and genetic analysis.
- Identification of genetic determinants conferring the susceptibility to cockroach sensitization. Asthma is the most prevalent serious chronic illness of children in the U.S. It is largely accepted that gene-environment interactions are responsible for the development of asthma, and that cockroach allergy is one of the major risk factors for the development of asthma. While there appears to be a rather clear relationship between allergen exposure and allergen sensitization, a dose-response relationship is mostly relevant for “susceptible” individuals, suggesting that cockroach sensitization is not a function of cockroach allergen exposure alone, and genetic susceptibility may be important. Our current study is to identify genetic determinants conferring the susceptibility to cockroach sensitization.
- Role of CD206 (MRC1[human] and MR[mouse]) in mediating cockroach allergen induced immune responses and lung inflammation. It is recognized that complex allergens contain multiple innate immune-activating components, which trigger the activation of mucosal innate immune cells that subsequently promote Th2-polarized adaptive immune responses and IgE responsiveness in susceptible individuals. CD206 has been shown to mediate the uptake of diverse native allergens by DCs and to determine allergen-induced T cell polarization. Our study is to investigate the role of CD206 in mediating cockroach allergen-induced allergic responses in vitro and in mouse models of asthma.
- Functional effects of TGF-beta1 on mesenchymal stem cell mobilization in cockroach allergen induced asthma. Mesenchymal stem cells (MSCs) have been suggested to participate in immune regulation and airway repair/remodeling. Transforming growth factor β1 (TGFβ1) is critical in the recruitment of stem/progenitor cells for tissue repair, remodeling and cell differentiation. In our study, we sought to investigate the role of TGFβ1 in MSC migration in allergic asthma.
- Functional significance of environmental chemical-aryl hydrocarbon receptor (AhR) axis in modulating allergic sensitization. Aryl hydrocarbon receptor (AhR) is a multifunctional regulator that senses and responds to environmental stimuli. Recent studies demonstrated that AhR can mediate an important immune response induced by polycyclic aromatic hydrocarbon (PAH), a major component in airborne particulate matter (APM) that is associated with increased asthma morbidity. Our study is to test the functional significance of environmental chemical-AhR axis in modulating allergic sensitization.
Do D, Zhao YL, Gao PS. Cockroach Allergen Exposure and Risk of Asthma. Allergy 2016; 71: 463–474.
Qu J, Do D, Zhou YF, Luczak E, Mitzner W, Anderson ME, Gao PS. Oxidized CaMKII Promotes Asthma through the Activation of Mast Cells. JCI Insight 2017; DOI: 10.1172.
Zhou Y, Do D, Ishmael FT, Squadrito ML, Tang HM, Tang HL, Hsu MH, Qiu L, Li C, Zhang Y, Becker KC, Wan M, Huang SK, Gao PS. Mannose Receptor Modulates Macrophage Polarization and Allergic Inflammation through miR-511-3p. J Allergy Clin Immunol 2018; 141(1):350-364.e8; PMID: 28629744.
Qiu L, Zhang Y, Do D, Ke X, Zhang S, Lambert K, Kumar S, Hu C, Zhou Y, Ishmael FT, Gao PS. miR-155 Modulates Cockroach Allergen and Oxidative Stress-Induced Cyclooxygenase-2 in Asthma. Journal of immunology 2018 (Accepted on June 1st).
Ke X, Do D, Li C, Zhao Y, Kollarik M, Fu Q, Wan M, Gao PS. Ras homolog family member A/Rho-associated protein kinase 1 signaling modulates lineage commitment of mesenchymal stem cells in asthmatic patients through lymphoid enhancer–binding factor 1. J Allergy Clin Immunol 2018 (Accepted on August 27).