Jack Elias, MD
Research & Publications
My laboratory is focused on the cellular and molecular events that are involved in the pathogenesis of injury and repair in the lung. We are particularly interested in the responses in human lung diseases and animal models of these diseases including asthma, chronic obstructive lung disease, pulmonary fibrosis and acute lung injury. Our studies have defined the cellular sources, regulation and effector profiles of many inflammatory, anti-inflammatory and remodeling cytokines in the lung including IL-1, IL-6, IL-11, leukemia Inhibitory factor, transforming growth factor-beta, vascular endothelial cell growth factor, IL-13 and gamma-interferon. These studies highlighted the cytokine networks that regulate their production, the transcriptional and post-transcriptional mechanisms that mediate these events, and their regulation by important respiratory states such as aeroallergen challenge, virus infection, innate immune activation and Th2 inflammation. In recent years, our lab has pioneered the use of lung specific constitutive and inducible overexpression transgenic mice to address the effector responses of these lung disease relevant genes. A recent refinement of this methodology utilizes triple transgenic methods to allow an investigator to control the timing of the expression of otherwise fetal-lethal transgene. By characterizing these mice we have been able to identify and are now studying many of the novel genes that are downstream of these moieties including chitinases and chitinase-like proteins, semaphorins, antiviral genes like MAVS and regulators of apoptosis. Whenever possible, findings in mice are taken directly to serum, plasma, DNA and tissue samples from well defined cohorts of human patients with these disorders and compared to appropriate controls.
Specialized Terms: Cell and Molecular biology of lung injury and repair; Asthma; COPD; Pulmonary fibrosis; acute lung injury; Cytokines; Inflammation; Internal Medicine; Pulmonary Diseases; Transgenic mice; genetically modified mice; Emphysema; Fibrosis; Inflammation
Asthma; Emphysema; Fibrosis; Inflammation; Internal Medicine; Lung; Pulmonary Fibrosis; Cytokines; Pulmonary Disease, Chronic Obstructive; Lung Injury; Acute Lung Injury
- Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosisLee CG, Hartl D, Lee GR, Koller B, Matsuura H, Da Silva CA, Sohn MH, Cohn L, Homer RJ, Kozhich AA, Humbles A, Kearley J, Coyle A, Chupp G, Reed J, Flavell RA, Elias JA. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13–induced tissue responses and apoptosis Journal Of Experimental Medicine 2009, 206: 1149-1166. PMID: 19414556, PMCID: PMC2715037, DOI: 10.1084/jem.20081271.
- Acidic Mammalian Chitinase Regulates Epithelial Cell Apoptosis via a Chitinolytic-Independent MechanismHartl D, He CH, Koller B, Da Silva CA, Kobayashi Y, Lee CG, Flavell RA, Elias JA. Acidic Mammalian Chitinase Regulates Epithelial Cell Apoptosis via a Chitinolytic-Independent Mechanism The Journal Of Immunology 2009, 182: 5098-5106. PMID: 19342690, PMCID: PMC2666938, DOI: 10.4049/jimmunol.0803446.
- Cigarette smoke selectively enhances viral PAMP– and virus-induced pulmonary innate immune and remodeling responses in miceKang MJ, Lee CG, Lee JY, Dela Cruz CS, Chen ZJ, Enelow R, Elias JA. Cigarette smoke selectively enhances viral PAMP– and virus-induced pulmonary innate immune and remodeling responses in mice Journal Of Clinical Investigation 2008, 118: 2771-2784. PMID: 18654661, PMCID: PMC2483678, DOI: 10.1172/jci32709.
- A Chitinase-like Protein in the Lung and Circulation of Patients with Severe AsthmaChupp GL, Lee CG, Jarjour N, Shim YM, Holm CT, He S, Dziura JD, Reed J, Coyle AJ, Kiener P, Cullen M, Grandsaigne M, Dombret MC, Aubier M, Pretolani M, Elias JA. A Chitinase-like Protein in the Lung and Circulation of Patients with Severe Asthma New England Journal Of Medicine 2007, 357: 2016-2027. PMID: 18003958, DOI: 10.1056/nejmoa073600.
- Semaphorin 7A plays a critical role in TGF-β1–induced pulmonary fibrosisKang HR, Lee CG, Homer RJ, Elias JA. Semaphorin 7A plays a critical role in TGF-β1–induced pulmonary fibrosis Journal Of Experimental Medicine 2007, 204: 1083-1093. PMID: 17485510, PMCID: PMC2118575, DOI: 10.1084/jem.20061273.
- Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathwayBlackburn MR, Lee CG, Young HW, Zhu Z, Chunn JL, Kang MJ, Banerjee SK, Elias JA. Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathway Journal Of Clinical Investigation 2003, 112: 332-344. PMID: 12897202, PMCID: PMC166289, DOI: 10.1172/jci16815.
- Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitroZheng T, Zhu Z, Liu W, Lee CG, Chen Q, Homer RJ, Elias JA. Cytokine regulation of IL-13Rα2 and IL-13Rα1 in vivo and in vitro Journal Of Allergy And Clinical Immunology 2003, 111: 720-728. PMID: 12704349, DOI: 10.1067/mai.2003.1383.