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The main interest of the Zimmermann laboratory is to decipher mechanisms of allergic diseases, primarily asthma. Eosinophils are the hallmark cell of allergic inflammation, including asthma. The long-term goals of the laboratory are:
Currently, we are focused on understanding the molecular mechanisms of eosinophil survival in allergic inflammation and asthma; in other words, our research is exploring why eosinophils are recruited and why they stay and lead to disease in some people and not in others.
We use a variety of approaches in our research, including animal modeling and ex vivo cell and molecular biology.
For more information about the lab, contact Nives Zimmermann at email@example.com.
Epstein TG, Kesavalu B, Bernstein CK, Ryan PH,
Bernstein JA, Zimmermann N, Lummus Z, Villareal MS, Smith AM, Lenz PH,
Bernstein DI. Chronic traffic pollution exposure is associated with eosinophilic, but not neutrophilic inflammation in older adult asthmatics. J Asthma. 50(9):983-9. 2013.
Kano G, Almanan M, Bochner BS, Zimmermann N. Mechanism of Siglec-8-mediated cell death in IL-5-activated eosinophils: Role for reactive oxygen species-enhanced MEK/ERK activation. J Allergy Clin Immunol. 132(2):437-45. 2013.
Mao H, Kano G, Hudson SA, Brummet M, Zimmermann
N, Zhu Z, Bochner BS. Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen. PLoS One. 28;8(6):e68143.
Zhu X, Mose E, Zimmermann N. Proton channel HVCN1 is required for effect or functions of mouse eosinophils. BMC Immunol. 14(1):24. 2013.
Collison A, Hatchwell L, Verrills N, Wark PA, de Siqueira AP, Tooze M, Carpenter H, Don AS, Morris JC, Zimmermann N, Bartlett NW, Rothenberg ME, Johnston SL, Foster PS, Mattes J. The E3 ubiquitin ligase midline 1 promotes allergen and rhinovirus-induced asthma by inhibiting protein phosphatase 2A activity. Nat Med. 19(2):232-7. 2013.
Lacy P, Willetts L, Kim JD, Lo AN, Lam B, Maclean EI, Moqbel R, Rothenberg ME, Zimmermann N. Agonist Activation of F-Actin-Mediated Eosinophil Shape Change and Mediator Release Is Dependent on Rac2. Int Arch Allergy Immunol. 156(2):137-147. 2011.
Arumugam M, Ahrens R, Osterfeld H, Kottyan LC, Shang X, Maclennan JA, Zimmermann N, Zheng Y, Finkelman FD, Hogan SP. Increased susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis. BMC Immunol. Feb 3;12:14. 2011.
Gao PS, Shimizu K, Grant AV, Rafaels N, Zhou L-F, Hudson SA, Konno S, Zimmermann N, Araujo MI, Ponte EV, Cruz AA, Nishimura M, Su S-N, Hizawa N, Beaty TH, Mathias RA, Rothenberg ME, Barnes KC, Bochner BS. Polymorphisms in the sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8) gene are associated with susceptibility to asthma. European Journal of Human Genetics. Jun, 2010.
Herbert DR, Orekov T, Roloson A, Ilies M, Perkins C, O'Brien W, Cederbaum S, Christianson DW, Zimmermann N, Rothenberg ME, Finkelman FD. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J Immunol. 184(11):6438-46. 2010.
Niese KA, Chiaramonte MG, Ellies LG, Rothenberg ME, Zimmermann N. The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis. Respir Res. 11(1):87. 2010.
Kottyan LC, Collier AR, Cao KH, Niese KA, Hedgebeth M, Radu CG, Witte ON, Khurana Hershey G, Rothenberg ME, Zimmermann N. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner. Blood. 114(13):2774-82. 2009.
Niese KA, Collier AR, Hajek AR, Cederbaum SD, O'Brien WE, Wills-Karp M, Rothenberg ME, Zimmermann N. Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice. BMC Immunology. 10:33. 2009.
Bergeron C, Boulet LP, Page N, Laviolette M, Zimmermann N, Rothenberg ME, Hamid Q. Influence of cigarette smoke on the arginine pathway in asthmatic airways: increased expression of arginase I. J Allergy Clin Immunol. 119:391-7. 2007.
Guo JP, Nutku E, Yokoi H, Schnaar RL, Zimmermann N, Bochner BS. Siglec-8 and Siglec-F: inhibitory receptors on eosinophils, basophils and mast cells. Allergy Clin. Immunol. Inter. – J. World Allergy Org. 19:54-59. 2007.
Brandt EB, Zimmermann N, Muntel EE, Yamada Y, Pope SM, Mishra A, Hogan SP, Rothenberg ME. The alpha4beta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to intestine. Clin Exp Allergy 36: 543-53. 2006.
Zimmermann N, Rothenberg ME. The arginine-arginase balance in asthma and lung inflammation. Eur J Pharmacol. 533:253-62. 2006.
Rothenberg ME, Doepker MP, Lewkowich IP, Chiaramonte MG, Stringer KF, Finkelman FD, MacLeod CL, Ellies LG, Zimmermann N. Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung. Proc Natl Acad Sci USA. 103:14895. 2006.
Yang M, Rangasamy D, Matthaei KI, Frew AJ, Zimmermann N, Mahalingam S, Webb DC, Tremethick DJ, Thompson PJ, Hogan SP, Rothenberg ME, Cowden WB, Foster PS. Inhibition of arginase I activity by RNA interference attenuates IL-13-induced airways hyperresponsiveness. J Immunol. 177:5595-603. 2006.
Pope SM, Fulkerson PC, Blanchard C, Saito Akei H, Nikolaidis NM, Zimmermann N, Molkentin JD, Rothenberg ME. Identification of a cooperative mechanism involving Interleukin-13 and eotaxin-2 in experimental allergic lung inflammation. J Biol Chem. 280:13952-61. 2005.
Zimmermann N, Doepker, MP, Witte DP, Stringer KF,Fulkerson PC, Pope SM, Brandt EB, Mishra A, King NE, Nikolaidis NM, Wills-Karp M, Finkelman FD, Rothenberg ME. Expression and regulation of small proline-rich protein 2 in allergic inflammation. J Respir Cell Mol Biol. 32(5):428-35. 2005.
Zimmermann N, Colyer JL, Koch L, Rothenberg ME. Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1. BMC Immunol. 6:7. 2005.
Pope SM, Zimmermann N, Stringer KF, Karow ML, Rothenberg ME. The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol. 175(8):5341-50. 2005.
Fulkerson PC, Zhu H, Williams DA, Zimmermann N, Rothenberg ME. CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism. Blood. 106(2):436-43. 2005.
Zimmermann N, Mishra A, King NE, Fulkerson PC, Doepker MP, Nikolaidis NM, Kindinger LE, Moulton EA, Aronow BJ, Rothenberg ME. Transcript signatures in experimental asthma: identification of STAT6-dependent and -independent pathways. J Immunol. 172:1815-1824. 2004.
Fulkerson PC, Zimmermann N, Brandt EB, Muntel EE, Doepker MP, Kavanaugh JL, Mishra A, Witte DP, Zhang H, Farber JM, Yang M, Foster PS, Rothenberg ME. Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-gamma (Mig, CXCL9). Proc Natl Acad Sci USA 101(7):1987-92. 2004.
King NE, Zimmermann N, Pope SM, Fulkerson PC, Nikolaidis NM, Mishra A, Witte DP, Rothenberg ME. Expression and regulation of a disintegrin and metalloproteinase (ADAM) 8 in experimental asthma. Am J Respir Cell Mol Biol. 31:257-65. 2004.
King NE, Rothenberg ME, Zimmermann N. Arginine in asthma and lung inflammation. J Nutrition 134:2830S-2836S. 2004.
Fulkerson PC, Zimmermann N, Hassman LM, Finkelman FD, Rothenberg ME. Pulmonary chemokine expression is coordinately regulated by STAT1, STAT6 and IFN-gamma. J Immunol. 173: 7565-74. 2004.
Yang M, Hogan SP, Mahalingam S, Matthaei KI, Dent L, McKenzie ANJ, Young IG, Pope SM, Zimmermann N, Rothenberg ME, Foster PS. Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity. J Allergy Clin Immunol. 112: 935-943. 2003.
Brandt EB, Strait RT, Hershko D, Wang Q, Muntel EE, Scribner TA, Zimmermann N, Finkelman FD, Rothenberg ME. Mast cells are required for experimental oral allergen-induced diarrhea. J Clin Invest. 112: 1666-1677. 2003.
Nikolaidis NM, Zimmermann N, King NE, Mishra A, Pope SM, Finkelman FD, Rothenberg ME. Trefoil factor-2 is an allergen-induced gene regulated by Th2 cytokines and STAT6 in the lung. Am J Respir Cell Mol Biol. 112: 1666-1677112. 2003.
Aizawa H, Zimmermann N, Carrigan PE, Lee JJ, Rothenberg ME, Bochner BS. Molecular analysis of human Siglecs-8 orthologs relevant to mouse eosinophils: identification of a mouse orthologs of Siglec-5 (mSiglec-F) and Siglec-10 (mSiglec-G). Genomics. 82:521-530. 2003.
Zimmermann N, King NE, Laporte J, Yang M, Mishra A, Pope SM, Muntel EE, Witte DP, Pegg AA, Foster PS, Hamid Q, Rothenberg ME. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest. 111(12):1863-74. 2003.
Zimmermann N, Hershey, GKK, Foster SP, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol. 111:227-243. 2003.
Zimmermann N, Rothenberg ME. Receptor internalization is required for eotaxin-induced responses in human eosinophils. J Allergy Clin Immunol. 111:97-105. 2003.
Pope SM, Brandt EB, Mishra A, Hogan SP, Zimmermann N, Matthaei KI, Foster, PS, Rothenberg ME. Interleukin-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism. J Allergy Clin Immunol 108:594-601. 2001.
Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, Foster PS, Rothenberg ME. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2:353-360. 2001.
Zimmermann N., Hogan SP, Mishra A, Brandt EB, Bodette TR, Finkelman FD, Rothenberg ME. Murine Eotaxin-2: a constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression. J Immunol. 165:5839-5846. 2000.
Zimmermann N, Daugherty BL, El-Awar FY, Moulton EA, Kavanaugh JL, Rothenberg ME. Analysis of the CC chemokine receptor 3 gene reveals a complex 5’ exon organization, a functional role for the untranslated exon 1, and a broadly active promoter. Blood. 96:2346-2354. 2000.
Zimmermann N, Daugherty BL, Stark JE, Rothenberg ME. Molecular analysis of CCR-3 events in eosinophilic cells. J Immunol. 164:1055-1064. 2000.
Rosa Rosa L, Zimmermann N, Bernstein JA, Rothenberg ME, Hershey GKK. The R576 IL-4 receptor alpha allele correlates with asthma severity. J Allergy Clin Immunol. 104:1008-1014. 1999.
Rothenberg ME, Zimmermann N, Mishra A, Brandt S, Hogan S, Foster PS. Chemokines and chemokine receptors: their role in allergic airway disease. J Clin Immunol. 19:250-265. 1999.
Zimmermann N, Conkright JJ, Rothenberg ME. CC chemokine receptor-3 undergoes prolonged ligand-induced internalization. J Biol Chem. 274:12611-12618. 1999.
Matthews AN, Friend DS, Zimmermann N, Sarafi MN, Luster AD, Pearlman E, Wert SE, Rothenberg ME. Eotaxin is required for the baseline level of tissue eosinophils. Proc Natl Acad Sci USA. 95: 6273-6278. 1998.
Gleich LL, Zimmermann N, Li YQ, Wang X, Gluckman JL. Angiogenic inhibition for the treatment of head and neck cancer. Anticancer Res. 18: 2607-2609. 1998.
Zimmermann N, Bernstein J, Rothenberg ME. Polymorphisms in the human CC chemokine receptor-3 gene. Biochim Biophys Acta. 1442:170-176. 1998.
Zimmermann N, Cavanaugh PF, Jr., Doney MK, Haq N, Gluckman JL, Pavelic ZP. Development of a MIMIC-based polymerase chain reaction technique for the analysis of prostaglandin endoperoxide H synthase isoenzyme cDNAs. Analyt Biochem. 251; 110-113. 1997.
Pavelic ZP, Lasmar M, Pavelic L, Sorensen C, Stambrook PJ, Zimmermann N, Gluckman JL. Absence of retinoblastoma gene product in human primary oral cavity carcinomas. Euro J Cancer 32B; 347-351. 1996.
Hecht D, Zimmermann N, Bedford M, Avivi A, Yayon A. Identification of fibroblast growth factor 9 (FGF9) as a high affinity, heparin dependent ligand for FGF receptors 3 and 2 but not for FGF receptors 1 and 4. Growth Factors 12; 223-233. 1995.
Zimmermann N, Ajdukovic N. Interleukin 2 and Interleukin 4 induced proliferation of T-lymphocytes. Medicinar. 37; 89- 95. 1992.
Zhu X, Zimmermann N. Eosinophil Chemotaxis. In: Lee JJ, Rosenberg HF (eds): Eosinophils in Health and Disease. London: Elsevier Inc, p. 121-131. 2013.
Zimmermann N, Rothenberg ME. Role of the eotaxin subfamily of chemokines in allergic eosinophilic inflammation. In: Eissa NT, Huston DP, Lenfant C (eds). Lung Biology in Health and Disease: Therapeutic Targets of Airway Inflammation. New York: Marcel Dekker Inc, p.421-464. 2003.
Dr. Zimmermann and summer student Megan Hedgebeth isolate human eosinophils.
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