Bethany B. Moore, Ph.D.
Professor of Internal Medicine,
Division of Pulmonary and Critical Care Medicine
Professor of Microbiology and Immunology
bmoore@umich.edu


Research Interests

My laboratory has two basic areas of interest. Our primary focus involves the pathogenesis of pulmonary fibrosis and the second interest involves infectious complications of bone marrow transplantation. Pulmonary fibrosis is a disease, often of unknown etiology, that results in the progressive accumulation of extracellular matrix (collagen) deposition within the lung resulting in a loss of gas exchange and death from respiratory insufficiency. The excessive collagen deposition that occurs in fibrosis is the result of activation and differentiation of fibroblasts into cells called myofibroblasts which contract the lung architecture. The combination of this contractile phenotype with the increased collagen synthetic capacity of these cells makes them the pathologic entity in this disease process. Many clinical associations suggest that viral infections may be associated with fibrotic illness. Thus, my laboratory is working to understand how viral infections impact the development of pulmonary fibrosis. We also study the contribution of a novel cell type, the fibrocyte, to pulmonary fibrogenesis and try to understand how extracellular matrix interactions with lung cells influence outcomes.  Current fibrosis projects are studying influenza A infection as a predisposing factor in pulmonary fibrosis and are looking at how a matricellular protein, periostin, can influence fibroblast pro-fibrotic responses.  We have translational studies exploring Idiopathic Pulmonary Fibrosis plasma proteins and circulating cell phenotypes as biomarkers for disease progression.

The other area of interest in our laboratory involves studying bacterial and viral
infections following bone marrow transplantation (BMT).Patients who undergo BMT remain more susceptible to lung infections for years post-BMT. Thus, we developed an animal model to study this question. Following syngeneic or allogeneic BMT, mice are more susceptible to infection with the nosocomial pathogen Pseudomonas aeruginosa and the bacteria Streptococcus pneumoniae and Staphylococcus aureus.  Additionally, BMT mice are more susceptible to herpesviral infections despite bone marrow reconstitution. We have determined that this increased susceptibility to bacterial pathogens relates to increased production of prostaglandin E2 post-BMT. The increased PGE2 production impairs the phagocytic and killing ability of the donor-derived alveolar macrophages against bacteria via the upregulation of IL-1 receptor associated kinase (IRAK-M) and the activation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN).   In the setting of viral infection, transforming growth factor beta (TGFβ) plays a role in the inhibition of anti-viral effector T cell responses. Current BMT projects are exploring epigenetic regulation of PGE2 expression and scavenger receptor profiles in alveolar macrophages post-BMT.  Additionally, we are exploring the role that TGFβ and IL-17 play in regulating the lung pathology that can occur post herpesviral-infection and we are moving into translational studies in human lung macrophages from control and BMT patients.

Recent Publications

Vannella, KM, Luckhardt, TR, Wilke, CA, van Dyk, LF, Toews, GB and BB Moore. 2010. Latent herpesvirus infection augments experimental pulmonary fibrosis. Am.J. Respir. Crit. Care Med., 181:465-77.

Coomes, S.M., Wilke, C.A., Moore, T.A. and B.B. Moore.  2010.  Induction of Transforming Growth Factor-β1, not Regulatory T cells, Impairs Anti-Viral Immunity in the Lung Following Bone Marrow Transplant J. Immunol.184(9):5130-40.

Hubbard, L.N., M.N. Ballinger, P.E. Thomas, C.A. Wilke, T.J. Standiford, K.S. Kobayashi, R.A. Flavell and B.B. Moore. 2010. A role for IRAK-M in PGE2-Induced Immunosuppression Post-Bone Marrow Transplantation. J. Immunol. 184(11):6299-308.

Stoolman, J.S., Vannella, K.M., Coomes, S.M, Wilke, C.A., Sisson, T.H., Toews, G.B. and B.B. Moore. 2010. Latent Infection by Gammaherpesvirus Stimulates Pro-Fibrotic Mediator Release from Multiple Cell Types. Am. J. Physiol. Lung Cell Mol. Physiol. 300(2):L274-85. PMID 2103691

Hubbard, LLN, Wilke, CA, White, ES and B.B. Moore. 2011. Deletion of PTEN in alveolar macrophages post-BMT restores opsonized phagocytosis and host defense. Am. J. Respir. Cell Mol Biol.45(5):1050-8.. PMID: 21527775.

Coomes, SM, Farmen, S, Wilke, CA, Laouar, Y and BB Moore. 2011. Severe gammaherpesvirus-induced pneumonitis and fibrosis in syngeneic bone marrow transplant mice is related to effects of transforming growth factor-beta on multiple cell types. Am. J. Pathol. 179(5):2382-96. PMID: 21924228

Naik, PN, Horowitz, JC, Moore, TA, Wilke, CA, Toews, GB and BB Moore, 2012, Pulmonary fibrosis induced by γherpesvirus in aged mice is associated with increased fibroblast responsiveness to TGFβ,  J Gerontol A Biol Sci Med Sci. 67(7):714-25.

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