Annette T. Hastie, Ph.D.
Associate Professor of Medicine

A.B., 1968 Oberlin College, Biology
Ph.D, 1975 University of Pittsburgh., Microbiology

Clinical Interests

Asthma and COPD

Research Interests

NIH funded studies examining inflammation in airway disease, either asthma or chronic obstuctive pulmonary disease (COPD) are principal interest.  Patients with asthma and chronic obstructive pulmonary disease are heterogeneous groups, potentially identified by differing patterns of inflammatory cells and mediators in subgroups of each disease.  Microarray assessment of proteins in airway secretions from subjects with different disease states over a range of severity are in progress.  Identified proteins are examined for association with cells, functional changes and gene variation.  Further interests are on airway epithelial cell function, and the interaction of epithelial cells with infiltrating leukocytes to stimulate fibroblast and myofibroblast production of extracellular matrix and inflammatroy mediators.  Additional studies investigate changes in cytoskeletal organization, primarily proteins such as VASP, and the heat shock proteins, which are involved in actin dynamics, cell-cell, and cell-matrix interaction of airway epithelial cells, and fibroblasts/ myofibroblasts, which are crucial for repair and replacement processes following inflammatory injury, and which may become dysregulated in these diseases. 

Selected Publications

Published Papers:
AT Hastie, M Wu, GC Foster, GA Hawkins, V Batra, KA Rybinski, R Cirelli, JG Zangrilli, SP Peters. “Alterations in vasodilator-stimulated phosphoprotein (VASP) phosphorylation:  associations with asthmatic phenotype, airway inflammation and b₂-agonist use” Respir Res 2006; 7:25. 

Comhair SA, Ricci KS, Arroliga M, Lara AR, Dweik RA, Song W, Hazen SL, Bleecker ER, Busse WW, Chung KF, Gaston B, Hastie AT, Hew M, Jarjour N, Moore W, Peters S, Teague WG, Wenzel SE, Erzurum SC for the Severe Asthma Research Program of the National Heart, Lung and Blood Institute, "Correlation of systemic superoxide dismutase deficiency to airflow obstruction in asthma."  Am J Respir Crit Care Med. 2008 Aug 1; 172 (3): 306-13.

Batra V., Musani A.I., Hastie AT, Khurana S., Carpenter K.A., Zangrilli J.G., Peters S.P.  Increasing Transforming Growth Factor in bronchoalveolar lavage fluid from asthmatics and its effect on a-smooth muscle actin and collagen synthesis by human lung fibroblasts.  2004.  Clin. Exp. Allergy 34:437-444.

Robertson N.M., Zangrilli J.G., Steplewski A., Hastie A., Lindemeyer R.G., Planeta M.A., Smith M.K., Innocent N., Musani A., Pascual R., Peters S., Litwack G.  Differential expression of TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors in allergic asthmatics following segmental antigen challenge:  Evidence for a role of TRAIL in eosinophil survival.  2002.  J. Immunol.  169:5986-5996.

Hastie AT, Kraft WK, Nyce KB, Zangrilli JG, Musani AI, Fish JE, Peters SP. Asthmatic epithelial cell proliferation and stimulation of collagen production. Human asthmatic epithelial cells stimulate collagen type III production by human lung myofibroblasts after segmental allergen challenge. 2002. Am J Respir Crit Care Med. 165:266-272.

Hastie AT, Peters SP. Interactions of allergens and irritants in susceptible populations in producing lung dysfunction: implications for future research. 2001. Environ Health Perspect Suppl. 109, Suppl. 4:605-607.

Ammit AJ, Hastie AT, Edsall LC, Hoffman RK, Amrani Y, Krymskaya VP, Kane SA, Peters SP, Penn RB, Spiegel S, Panettieri RA, Jr. Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma. 2001. FASEB J. 15:1212-1214.

Colavita AM, Hastie AT, Musani AI, Pascual RM, Reinach AJ, Lustine HT, Galati SA, Zangrilli JG, Fish JE, Peters SP. Kinetics of IL-10 production after segmental allergen challenge of atopic asthmatic subjects. 2000. J Allergy Clin Immunol. 106:880-886.

Zangrilli J., Robertson N.M., Shetty A., Wu J., Hastie A.T., Fish J.E., Litwack G., Peters S.P. Effect of IL-5, glucocorticoid, and FAS ligation on Bcl-2 homologue expression and caspase activation in circulating human eosionophils. 2000. Clin Exp Immunol 120:12-21.

Hastie, A.T., Everts, K.B., Shaver, J.R., Cirelli, R., Zangrilli, J., Pollice, M.B., Fish, J.E. Peters, S.P. b2-Agonist elevated stress response in human bronchial epithelial cells in vivo and in vitro. 1997. Lung 175:287-298.

Hastie, A.T., Everts, K.B., Zangrilli, J., Shaver, J.R., Pollice, M.B., Fish, J.E., Peters, S.P. Elevated Hsp27 stress protein in mild allergic inflammation protects airway epithelium from H2SO4 effects. 1997. Am. J. Physiol: Lung Cell Mol. Physiol. 273:L401-L409.

Shaver J.R., Zangrilli J., Cho S.-K., Cirelli R.A., Pollice M.B., Hastie, A.T., Fish J.E., Peters S.P. Kinetics of development and recovery of the lung from IgE-mediated inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophil-active cytokines. 1997 Am.J.Respir.Crit.CareMed. 155:442-448 .

Hastie, A.T., Everts, K.B., Zangrilli J., Shaver, J.R., Pollice, M.B., Fish, J.E., Peters, S.P. IL-1b release frombronchial epithelial cells and bronchoalveolar lavage cells from allergic and normal humans following segmental challenge with ragweed. 1996. Cytokine 8:730-739.

Hastie, A. T. Isolation of respiratory cilia. Methods Cell Biol. 47:93-98 1995.

Abstracts:
Hastie AT, Moore WC, Meyers DA, Vestal PL, Krings JO, Smith RA, Li H, Peters SP, Bleecker ER.  Inflammatory Protein Analyses of Sputum from Human Subjects with Severe or Nonsevere Asthma.  Am J Respir Crit Care Med (2009);179:A3925

Hastie A.T., Carpenter K.A., Batra V., Zangrilli J.G., Fish J.E., Peters S.P. Vasodilator-stimulated phosphoprotein in human lung fibroblasts altered by growth factors in vitro. 3rd Triennial World Asthma Meeting 2001.

Batra V., Carpenter K.A., Hastie A.T., Zangrilli J.G., Fish J.E., Peters S.P. Effect of growth factors and cytokines on a-smooth muscle actin expression by human lung fibroblasts; lack of correlation with collagen type III synthesis. 3rd Triennial World Asthma Meeting 2001.

Hastie A.T., Kraft W.K., Nyce K.B., Zangrilli J.G., Fish J.E., Peters S.P. Airway epithelial cell proliferation and stimulation of collagen type III synthesis after segmental allergen challenge in human asthmatics. 3rd Triennial World Asthma Meeting 2001.

Zangrilli J., Galati S., Robertson N.M., Niazi S., Hastie A.T., Carpenter K., Pascual R., Fish J.E., Litwack G., Peters S.P. Soluble FAS and FAS ligand in BAL fluid from asthmatics following antigen challenge: immunoreactivity, apoptotic activity and molecular forms. 3rd Triennial World Asthma Meeting 2001.

Awsare BK, Pascual RM, Hastie AT, Panettieri RA Jr., Fish JE, Peters SP, Penn RB. Effects of TGFb1 on MAPK and G protein-coupled receptor (GPCR) signaling in human airway smooth muscle (HASM). Am J Respir Crit Care Med 163:A270 (2001).

Niazi S, Carpenter K, Apridonize T, Hastie AT, Robertson N, Fish JE, Peters SP, Zangrilli JG. Processing of caspases 8 and 9 and BID in human eosinophils undergoing apoptosis: effect of FAS ligation, glucocorticoid and IL-5. Am J Respir Crit Care Med 163:A321 (2001).

Hastie AT, Carpenter KA, Batra V, Zangrilli JG, Fish JE, Peters SP. Growth factor effect on vasodilator-stimulated phosphoprotein in human lung fibroblasts. Am J Respir Crit Care Med 163:A472 (2001).

Robertson NM, Zangrilli JG, Steplewski A, Lindemeyer RG, Hastie AT, Smith M, Musani A, Pascual R, Peters SP, Litwack G. Expression of TRAIL, DR4, DR5 and decoy receptors in allergic asthmatics following segmental antigen challenge. Am J Respir Crit Care Med 163:A606 (2001).

Batra V, Carpenter K, Hastie AT, Zangrilli JG, Fish JE, Peters SP. Increased a-smooth muscle actin in human lung fibroblasts stimulated with TGFb1, basic FGF and PDGF: lack of correlation with collagen type III synthesis. Am J Respir Crit Care Med 163:A786 (2001).

Musani AI, Hastie AT, Carpenter KA, Galati S, Pascual RM, Zangrilli JG, Fish JE, Peters SP. TGFb1 release from airway epithelial cells ex vivo after segmental allergen challenge in asthmatics and normals, modified by TNFa and bronchoalveolar lavage cells. Am J Respir Crit Care Med 163:A788 (2001).

Ammit AJ, Hastie AT, Hoffman RK, Kane SA, Edsall L, Peters SP, Speigel S, Panettieri RA, Jr. Sphingosine 1-phosphate (SPP) modulates human airway smooth muscle (HASM) proliferation and chemokine/cytokine secretion. Am J Respir Crit Care Med 161:A698 (2000).

Colavita AM, Hastie AT, Musani AI, Pascual RM, Reinach AJ, Zangrilli JG, Fish JE, Peters SP. IL-10 immunocytochemistry of BAL cells after segmental allergen challenge in asthmatics vs controls. Am J Respir Crit Care Med 161:A597 (2000).

Forteza R, Abraham J, Hastie A, Peters S, Salathe M, Conner GE. Segmental allergen challenge increases hyaluronic acid and tissue kallikrein in bronchoalveolar lavage of asthmatics. Am J Respir Crit Care Med 161:A599 (2000).

Hastie AT, Narula S, Zangrilli JG, Colavita AM, Musani AI, Pascual RM, Ammit AJ, Panettieri RA Jr., Fish JE, Peters SP. Increased RANTES expression in allergic asthmatic airway interstitium and smooth muscle after segmental allergen challenge. Am J Respir Crit Care Med 161:A247 (2000).

Musani AI, Galati S, Hastie AT, Colavita AM, Pascual RM, Reinach AJ, Zangrilli JG, Fish JE, Peters SP. A dissociation between IL-4 and IL-13 after segmental challenge in patients with asthma. Am J Respir Crit Care Med 161:A256 (2000).

Reinach AJ, Hastie AT, Narula S, Zangrilli JG, Colavita AM, Musani AI, Pascual RM, Fish JE, Peters SP. Prolonged IL-12 expression in airway tissue of asthmatics after segmental allergen challenge. Am J Respir Crit Care Med 161:A684 (2000).

Robertson NM, Zangrilli JG, Hastie A, Planeta MA, Smith MK, Lindemeyer RG, Lustine T, Peters S, Litwack G. Enchanced expression of Trail/APO2 in allergic asthmatics following segmental antigen challenge. Am J Respir Crit Care Med 161:A330 (2000).

Sambandam K, Zangrilli J, Robertson NM, Galati S, Hastie AT, Colavita A, Pascual R, Musani A, Reinach A, Fish JE, Peters SP. Soluble and in situ Fas and Fas ligand expression in the human airway after segmental allergen challenge. Am J Respir Crit Care Med 161:A335 (2000).

Lustine H.T., Zangrilli J.G., Hastie A.T., Reinach A.J., Colavita A.M., Pollice M., Fish J.E., Peters S.P. IL-1b and IL-1ra; their interaction and modulation of inflammation in asthmatic airways. Amer. J. Respir. Crit. Care Med. 159:A21. 1999.

Reinach A.J., Zangrilli J.G., Lustine H.T., Colavita A.M., Hastie A.T., Pollice M., Fish J.E., Peters S.P. Role of IL-12 in allergic asthma and inflammation. Amer. J. Respir. Crit. Care Med. 159:A255. 1999.

Hastie A.T., Zangrilli J.G., Colavita A.M., Reinach A.J., Lustine H.T., Pollice M., Fish J.E., Peters S.P. Kinetics of IL-11 release after segmental challenge in allergic asthmatics. Amer. J. Respir. Crit. Care Med. 159:A451. 1999.

Hastie A.T., Zangrilli J.G., Colavita A.M., Reinach A.J., Lustine H.T., Pollice M., Fish J.E., Peters S.P. Granulocyte-macrophage colony stimulating factor (GM-CSF). Kinetics in recovery from allergen (Ag) challenge in allergic asthmatics (AA). Amer. J. Respir. Crit. Care Med. 159:A453. 1999.

Colavita A.M., Zangrilli J.G., Reinach A.J., Lustine H.T., Hastie A.T., Pollice M., Fish J.E., Peters S.P. IL-10 and its modulation by glucocorticoids in allergic asthma. Amer. J. Respir. Crit. Care Med. 159:A854. 1999.

Zhuang J., Hsu P., Everts K., Ogawa K., Fish J.E., Hastie A.T. Sequences of two mammalian b-like dynein heavy chains; one missing the third nucleotide binding site. 1996. Mol. Biol. Cell 7:567a.

Hastie, A.T., Everts, K.B., Zangrilli, J., Shaver, J.R., Diaz, A., Fish, J.E., Peters, S.P. Increased stimulation of lung fibroblast collagen synthesis by airway epithelium from allergic asthmatics after segmental allergen lung challenge. Amer. J. Respir. Crit. Care Med. 153:A401. 1996.

Hastie, A.T., Everts, K.B., Shaver, J.R., Zangrilli, J., Pollice, M., Fish, J.E., Peters, S.P. Proliferation of allergic asthmatic airway epithelial cells after segmental allergen lung challenge corresponding to granulocyte/macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-b (TGFb). Amer. J. Respir. Crit. Care Med. 153:A728. 1996.

Shaver, J.R., Zangrilli, J., Cho, S.-K., Pollice, M., Cirelli, R.A., Hastie A.T., Everts, K.B., Fish, J.E., Peters, S.P. IL-3, IL-5, and GM-CSF have different patterns of production during recovery from IgE-mediated inflammation in allergic asthmatics. Amer. J. Respir. Crit. Care Med. 153:A793. 1996.

Hastie, A.T., Everts, K.B., Shaver, J.R., Zangrilli, J., Cirelli, R.A., Pollice, M., Fish, J.E., Peters, S.P. Stimulation of airway epithelial cell proliferation by infiltrating leukocytes after segmental allergen lung challenge. Amer. J. Respir. Crit. Care Med. 151:A189. 1995.

Hastie, A.T., Everts, K.B., O'Connor, J., Tolino, M., Leighton, B., Pollice, M., Fish, J.E., Peters, S.P. Mild inflammatory response to allergen induces increased levels of 27 KD stress protein in airway epithelial cells and protects cells from effects of H2SO4. Amer. J. Respir. Crit. Care Med. 151:A703. 1995.

Cho, S.-K., Zangrilli, J., Kim, C.-J., Hastie, A.T., Cirelli, R.A., Shaver, J.R., Fish, J.E., Peters, S.P. Patterns of tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), and IL-1 receptor antagonist (IL-1ra) after antigen challenge. Amer. J. Respir. Crit. Care Med. 151:A136. 1995.