Brooke Mossman, Ph.D.

Professor of Pathology

Research Program: Cell Signaling & Growth Control
VCC Membership Level: Member Scientist

Contact Information

218 Health Science Research Facility
149 Beaumont Avenue
University of Vermont
Burlington, VT 05405

ph: (802) 656-0382
f: (802) 656-8892
Brooke.Mossman@uvm.edu

Biography

Dr. Mossman has been studying the mechanisms of environmental lung disease for over 25 years and has generated over 275 publications. Her interest in the field began with graduate training in the laboratory of Andrew Sivak, Ph.D., at the New York University Institute of Environmental Medicine, where she worked on the effects of phorbol esters in skin carcinogenesis. She completed her Ph.D. in the laboratory of John E. Craighead, M.D., in the Department of Pathology at UVM. She then pursued postdoctoral research on interactions of asbestos and cigarette smoke in lung tumors with Edward Bresnick, Ph.D., in the Department of Biochemistry at UVM. She is a past director of the Cell & Molecular Biology Program at UVM and now directs the Environmental Pathology Program. Her current research focuses on cell signaling by asbestos, silica, and oxidant stress in cells of the respiratory tract. She has remained an NIH-funded investigator throughout her career.

Research

Dr. Mossman's research group is studying the molecular mechanisms of chemical and physical carcinogenesis as well as fibrotic lung disease caused by asbestos and other inhaled particulates (e.g., silica, glass, and refractory ceramic fibers). She is also examining the relationship between active oxygen species and lung disease by these environmental pollutants. Epithelial cells, mesothelial cells and and fibroblasts of the respiratory tract in both cell and organ cultures are used to evaluate molecular, cytotoxic and proliferative changes after exposure to asbestos and other compounds. One of several projects is aimed at dissecting second messenger pathways including alterations in protein kinase cascades which may be involved in causing changes in gene expression in human mesothelioma cells. In an inter-institutional program project grant, she is exploring modification of these signaling cascades in a mouse xenograft model of human mesothelioma using targeted approaches including acid-prepared mesoporous spheres for drug delivery.

Recent Publications

Dostert C, Petrulli V, Van Bruggen R, Steele C, Mossman BT and Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science

Barlow CA, Kitiphongspattana K, Siddiqui N, Roe MW, Mossman BT, Lounsbury KM: Protein kinase A-mediated CREB phosphorylation is an oxidant-induced survival pathway in alveolar type II cells. Apoptosis 13:681-692, 2008

Manning CB, Sabo-Attwood T, Robledo RF, MacPherson MB, Rincon M, Vacek P, Hemenway D, Taatjes DJ, Lee PJ, and Mossman BT: Targeting the MEK1 cascade in lung epithelium inhibits proliferation and fibrogenesis by asbestos. Am J Respir Cell Mol Biol 38:618-626, 2008

Ramos-Nino ME, Blumen SR, Sabo-Attwood T, Pass H, Carbone M, Testa JR, Altomare DA and Mossman BT: HGF mediates cell proliferation of human mesothelioma cells through a PI3K/MEK5/Fra-1 pathway. Am J Respir Cell Mol Biol 209-217, 2008

Levis J, Loi R, Butnor KC, Vacek, P, Steele C, Mossman BT and Weiss, DJ: Decreased asbestos-induced lung inflammation and fibrosis after radiation and bone marrow transplantation. Am J Respir Cell Mol Biol 38:16-25, 2008

Ramos-Nino ME, Blumen SR, Pass H, and Mossman BT: Fra-1 governs cell migration via modulation of CD44 expression in human mesotheliomas. (On-line journal) Mol Cancer 6:81, 2007

Barlow C, Shukla A, Mossman B, and Lounsbury K: Asbestos-mediated CREB phosphorylation is regulated by protein kinase A and extracellular signal regulated kinases 1/2. Am J Physiol: Lung Cell Mol Physiol 292:L1361-L1369, 2007

Haegens A, Barrett TF, Gell J, Shukla A, MacPherson M, Vacek P, Poynter ME, Butnor KJ, Janssen-Heininger YM, Steele C, and Mossman BT: Airway epithelial NF-κB activation modulates asbestos-induced inflammation and mucin production in vivo. J Immunol 178:1800-1808, 2007

Shukla A, Lounsbury KM, Barrett TF, Gell J, Rincon M, Butnor KJ, Taatjes DJ, Davis GS, Vacek P, Nakayama KI, Nakayama K, Steele C, and Mossman BT: Asbestos-induced peribronchiolar cell proliferation and cytokine production are attenuated in lungs of protein kinase Cδ (PKC-δ) knockout mice. Am J Pathol 170:140-151, 2007

Blumen SR, Cheng K, Ramos-Nino ME, Taatjes DJ, Weiss DJ, Landry CC, and Mossman BT: Unique uptake of acid-prepared mesoporous spheres by lung epithelial and mesothelioma cells. Am J Respir Cell Molec Biol 36:333-342, 2007

Li M, Liu R-M, Timblin CR, Meyer SG, Mossman BT, and Fukagawa NK: Age affects ERK1/2 and NRF2 signaling in the regulation of GCLC expression. J Cell Phys 206:518-525, 2006

Lee PJ, Zhang X, Shan P, Ma B, Lee CG, Homer RJ, Zhu Z, Rincon M, Mossman BT, and Elias JA: ERK1/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo. J Clin Invest 116:163-173, 2006

Barlow CA, Shukla A, Mossman BT, and Lounsbury KM: Oxidant-mediated CREB activation: calcium regulation and role in apoptosis of lung epithelial cells. Am J Resp Cell Molec Biol 34:7-15, 2006

Shukla A, Barrett TF, Nakayama KI, Nakayama K, Mossman BT, and Lounsbury KM: Transcriptional upregulation of MMPs 12 and 13 by asbestos occurs via a PKCδ-dependent pathway in murine lung, FASEB J 20:997-999, 2006

Mossman BT, Lounsbury KM, and Reddy S: Oxidants and signaling by MAPK in lung epithelium. Am J Resp Cell Molec Biol 34:666-669, 2006

O'Hara KA, Nemec AA, Alam J, Klei, LR, Barchowsky A, and Mossman BT: Chromium (VI) inhibits heme oxygenase-1 expression in vivo and in arsenic-exposed human airway epithelial cells. J Cell Physiol 209:113-121, 2006

Yang H, Bocchetta M, Kroczynska B, Elmishad AG, Chen Y, Liu Z, Bubici C, Mossman BT, Pass HI, Testa JR, Franzoso G, and Carbone M: TNF-α inhibits asbestos induced cytotoxicity via a NF-κB dependent pathway, a possible mechanism for asbestos induced oncogenesis. Proc Natl Acad Sci USA 103:10397-10402, 2006

Kroczynska BR, Cutrone R, Bocchetta M, Yang H, Elmishad AG, Ramos-Nino M, Mossman BT, Pass HI, and Carbone M: Crocidolite asbestos and SV40 are cocarcinogens in human mesothelial cells and in causing mesothelioma in hamsters. Proc Natl Acad Sci USA 103:14128-14133, 2006

Li M, Chiu JF, Mossman BT, and Fukagawa NK: Down regulation of MnSOD through phosphorylation of FOXO3a by AKT in explanted VSMC from old rats. J Biol Chem 281:40429-40439, 2006

Haegens A, van der Vliet A, Butnor KJ, Heintz N, Taatjes D, Hemenway D, Vacek P, Freeman BA, Hazen SL, Brennan ML, and Mossman BT: Asbestos-induced lung inflammation and epithelial cell proliferation are altered in myeloperoxidase-null mice. Cancer Res 65:9670-9677, 2005

Ramos-Nino ME, Vianale G, Sabo-Attwood T, Mutti L, Porta C, Heintz N, and Mossman BT: Human mesothelioma cells exhibit tumor cell-specific differences in phosphatidylinositol 3-kinase /AKT activity that predict the efficacy of Onconase. Mol Cancer Ther 4:835-842, 2005

Sabo-Attwood T, Ramos-Nino M, Bond J, Butnor KJ, Heintz N, Gruber AD, Steele C, Taatjes DJ, Vacek P, and Mossman BT: Gene expression profiles reveal increased mCla3 (Gob5) expression and mucin production in a murine model of asbestos-induced fibrogenesis. Am J Pathol 167:1243-1256, 2005

Altomare DA, You H, Xiao G-H, Ramos-Nino, ME, Skele KL, De Rienzo A, Jhanwar SC, Mossman BT, Kane AB, and Testa JR: Human and mouse mesotheloimas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Oncogene 24:6080-6089, 2005

Other Key Publications

Mossman BT, Bignon J, Corn M, Seaton A, Gee JBL. Asbestos: Scientific developments and implications for public policy. Science 1990 247: 294-301.