Immunodeficiency; mast cell progenitor homing / recruitment and its involvement in allergic disorders

MD: University of Buffalo, Buffalo, NY, 1997.

Residency: Pediatrics, Children's Hospital of Buffalo, Buffalo, NY, 2000.

Certification: American Board of Pediatrics, 2001; American Board of Allergy and Immunology, 2003.
 

Abonia JP, Putnam PE. Mepolizumab in eosinophilic disorders. Expert Rev Clin Immunol. 2011 Jul;7(4):411-7.

Debrosse CW, Franciosi JP, King EC, Buckmeier Butz BK, Greenberg AB, Collins MH, Abonia JP, Assa'ad A, Putnam PE, Rothenberg ME. Long-term outcomes in pediatric-onset esophageal eosinophilia. J Allergy Clin Immunol. 2011 Jul;128(1):132-8.

Franciosi JP, Hommel KA, Debrosse CW, Greenberg AB, Greenler AJ, Abonia JP, Rothenberg ME, Varni JW. Quality of life in paediatric eosinophilic oesophagitis: what is important to patients?Child Care Health Dev. 2011 Jun 15. Epub ahead of print.

Abonia JP, Castells M. Drug allergy in pediatric patients. Pediatr Ann. 2011 Apr;40(4):200-4.

Blanchard C, Stucke EM, Rodriguez-Jimenez B, Burwinkel K, Collins MH, Ahrens A, Alexander ES, Butz BK, Jameson SC, Kaul A, Franciosi JP, Kushner JP, Putnam PE, Abonia JP, Rothenberg ME. A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol. 2011 Jan;127(1):208-17, 217.e1-7.

Sherrill JD, Gao PS, Stucke EM, Blanchard C, Collins MH, Putnam PE, Franciosi JP, Kushner JP, Abonia JP, Assa'ad AH, Kovacic MB, Biagini Myers JM, Bochner BS, He H, Hershey GK, Martin LJ, Rothenberg ME. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol. 2010 Jul;126(1):160-5.e3.

DeBrosse CW, Collins MH, Buckmeier Butz BK, Allen CL, King EC, Assa'ad AH, Abonia JP, Putnam PE, Rothenberg ME, Franciosi JP. Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982-1999. J Allergy Clin Immunol. 2010 Jul;126(1):112-9.

Abonia JP, Blanchard C, Butz BB, Rainey HF, Collins MH, Stringer K, Putnam PE, Rothenberg ME. Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol. 2010 Jul;126(1):140-9.

Rayapudi M, Mavi P, Zhu X, Pandey AK, Abonia JP, Rothenberg ME, Mishra A. Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2010 Aug;88(2):337-46.

Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, Gober L, Kim C, Glessner J, Frackelton E, Thomas K, Blanchard C, Liacouras C, Verma R, Aceves S, Collins MH, Brown-Whitehorn T, Putnam PE, Franciosi JP, Chiavacci RM, Grant SF, Abonia JP, Sleiman PM, Hakonarson H. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010 Apr;42(4):289-91.

Food allergy; asthma; vaccine allergy; immunodeficiencies

MBBCh (MD): Ain Shams University, Cairo, Egypt 1978.

MS: Ain Shams University, Cairo, Egypt, 1982.

Residency: Internal Medicine/Pediatrics, Michigan State University, Hurley Medical Center, Flint, Mich.; Internal Medicine/Pediatrics, Wright State University, Dayton, Ohio, 1990-1992.

Fellowship: Allergy/Clinical Immunology, University of Texas Health Science Center, San Antonio, Texas, 1986-1987; Allergy/Clinical Immunology, Children's Hospital Medical Center, Cincinnati, Ohio, 1992-1995.

Certification: American Board of Internal Medicine, 1992; American Board of Pediatrics, 1992; American Board of Allergy and Immunology, 1995.

Sherrill JD, Gao PS, Stucke EM, Blanchard C, Collins MH, Putnam PE, Franciosi JP, Kushner JP, Abonia JP, Assa'ad AH, Kovacic MB, Biagini Myers JM, Bochner BS, He H, Hershey GK, Martin LJ, Rothenberg ME. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. J Allergy Clin Immunol. 2010 Jul;126(1):160-5.e3.

DeBrosse CW, Collins MH, Buckmeier Butz BK, Allen CL, King EC, Assa'ad AH, Abonia JP, Putnam PE, Rothenberg ME, Franciosi JP. Identification, epidemiology, and chronicity of pediatric esophageal eosinophilia, 1982-1999. J Allergy Clin Immunol. 2010 Jul;126(1):112-9. 

Assa'ad A. Eosinophilic gastrointestinal disorders. Allergy Asthma Proc. 2009 Jan-Feb;30(1):17-22. 

Assa'ad A. Gastrointestinal eosinophil-mediated disorders and their treatment. Curr Allergy Asthma Rep. 2009 Jan;9(1):26-9. 

Collins MH, Blanchard C, Abonia JP, Kirby C, Akers R, Wang N, Putnam PE, Jameson SC, Assa'ad AH, Konikoff MR, Stringer KF, Rothenberg ME. Clinical, pathologic, and molecular characterization of familial eosinophilic esophagitis compared with sporadic cases.Clin Gastroenterol Hepatol. 2008 Jun;6(6):621-9.

Stein ML, Villanueva JM, Buckmeier BK, Yamada Y, Filipovich AH, Assa'ad AH, Rothenberg ME. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008 Jun;121(6):1473-83, 1483.e1-4.

Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28. 

Gupta J, Grube E, Ericksen MB, Stevenson MD, Lucky AW, Sheth AP, Assa'ad AH, Khurana Hershey GK. Intrinsically defective skin barrier function in children with atopic dermatitis correlates with disease severity. J Allergy Clin Immunol. 2008 Mar;121(3):725-730.e2. 

Assa'ad A. Eosinophilic esophagitis: association with allergic disorders.Gastrointest Endosc Clin N Am. 2008 Jan;18(1):119-32; x.

Bullock JZ, Villanueva JM, Blanchard C, Filipovich AH, Putnam PE, Collins MH, Risma KA, Akers RM, Kirby CL, Buckmeier BK, Assa'ad AH, Hogan SP, Rothenberg ME. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007 Jul;45(1):22-31. 

Clinical Interests

Primary immunodeficiencies; BMT for primary immunodeficiencies; hemophagocytic lymphocytosis; post-BMT immune reconstruction 

Research Interests

Biology and genetics of hemophagocytic lymphohistiocytosis; investigation of hematopoietic cell transplantation for genetic immunodeficiencies; immunoreconstitution following pediatric stem cell transplantation 

Jodele S, Bleesing JJ, Mehta PA, Filipovich AH, Laskin BL, Goebel J, Pinkard SL, Davies SM. Successful early intervention for hyperacute transplant-associated thrombotic microangiopathy following pediatric hematopoietic stem cell transplantation.  Pediatr Transplant. 2010 Nov 5.

Marsh RA, Vaughn G, Kim MO, Li D, Jodele S, Joshi S, Mehta PA, Davies SM, Jordan MB, Bleesing JJ, Filipovich AH.  Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010 Dec 23;116(26):5824-31.

Marsh RA, Bleesing JJ, Filipovich AH. Using flow cytometry to screen patients for X-linked lymphoproliferative disease due to SAP deficiency and XIAP deficiency.J Immunol Methods. 2010 Oct 31;362(1-2):1-9.

Laskin BL, Goebel J, Davies SM, Khoury JC, Bleesing JJ, Mehta PA, Filipovich AH, Paff ZN, Lawrence JM, Yin HJ, Pinkard SL, Jodele S. Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT.  Bone Marrow Transplant. 2010 Aug 9.

Filipovich AH, Zhang K, Snow AL, Marsh RA. X-linked lymphoproliferative syndromes: brothers or distant cousins? Blood. 2010 Nov 4;116(18):3398-408.

Marsh RA, Madden L, Kitchen BJ, Mody R, McClimon B, Jordan MB, Bleesing JJ, Zhang K, Filipovich AH. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease. Blood. 2010 Aug 19;116(7):1079-82.

Marsh RA, Satake N, Biroschak J, Jacobs T, Johnson J, Jordan MB, Bleesing JJ, Filipovich AH, Zhang K. STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. Pediatr Blood Cancer. 2010 Jul 15;55(1):134-40.

Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program. 2009:127-31.

Nicolaou SA, Neumeier L, Takimoto K, Lee SM, Duncan HJ, Kant SK, Mongey AB, Filipovich AH, Conforti L. Differential calcium signaling and Kv1.3 trafficking to the immunological synapse in systemic lupus erythematosus. Cell Calcium. 2010 Jan;47(1):19-28.

Marsh RA, Villanueva J, Kim MO, Zhang K, Marmer D, Risma KA, Jordan MB, Bleesing JJ, Filipovich AH. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009 Jul;132(1):116-23.

Rheumatology; cytokine control of immune-mediated disorders and host protection against parasites, cytokine regulation of allergic disorders, cytokine regulation of lymphopoiesis; regulation of cytokine responses and mechanisms of lymphocyte activation and tolerance; anaphylaxis; transfusion-related acute lung injury

Khodoun MV, Strait R, Armstrong L, Yanase N, Finkelman FD. Identification of markers that distinguish IgE- from IgG-mediated anaphylaxis. Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12413-8.

Strait RT, Mahler A, Hogan S, Khodoun M, Shibuya A, Finkelman FD. Ingested allergens must be absorbed systemically to induce systemic anaphylaxis. J Allergy Clin Immunol. 2011 Apr;127(4):982-9.e1.

Perkins C, Yanase N, Smulian G, Gildea L, Orekov T, Potter C, Brombacher F, Aronow B, Wills-Karp M, Finkelman FD. Selective stimulation of IL-4 receptor on smooth muscle induces airway hyperresponsiveness in mice. J Exp Med. 2011 Apr 11;208(4):853-67.

Brandt EB, Munitz A, Orekov T, Mingler MK, McBride M, Finkelman FD, Rothenberg ME. Targeting IL-4/IL-13 signaling to alleviate oral allergen-induced diarrhea. J Allergy Clin Immunol. 2009 Jan;123(1):53-8.

Herbert 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. 2010 Jun 1;184(11):6438-46.

DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF Jr, Rothenberg ME, Finkelman FD. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med. 2009 Dec 21;206(13):2947-57.

Morris SC, Heidorn SM, Herbert DR, Perkins C, Hildeman DA, Khodoun MV, Finkelman FD. Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation. J Immunol. 2009 Feb 1;182(3):1429-38.

Khodoun M, Strait R, Orekov T, Hogan S, Karasuyama H, Herbert DR, Köhl J, Finkelman FD. Peanuts can contribute to anaphylactic shock by activating complement. J Allergy Clin Immunol. 2009 Feb;123(2):342-51.

Forbes EE, Groschwitz K, Abonia JP, Brandt EB, Cohen E, Blanchard C, Ahrens R, Seidu L, McKenzie A, Strait R, Finkelman FD, Foster PS, Matthaei KI, Rothenberg ME, Hogan SP. IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med. 2008 Apr 14;205(4):897-913.

Phelan JD, Orekov T, Finkelman FD. Cutting edge: mechanism of enhancement of in vivo cytokine effects by anti-cytokine monoclonal antibodies. J Immunol. 2008 Jan 1;180(1):44-8.

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. 2010 Jun 1;184(11):6438-46.

Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF Jr, Rothenberg ME, Finkelman FD. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med. 2009 Dec 21;206(13):2947-57.

Morris SC, Heidorn SM, Herbert DR, Perkins C, Hildeman DA, Khodoun MV, Finkelman FD. Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation. J Immunol. 2009 Feb 1;182(3):1429-38.

O'Connell AE. Kerepesi LA, Vandergrift GL, Van Winkle TJ, Herbert DR, Hooper DC, Pearce EJ and Abraham D. Lethal Mesocestoides Corti Infection in IL-4 Mice is Associated with Decreased Th2 and Increased Th1 Responses. Parasite Immunology.

Niewenhuizen N, Herbert DR, Lopata AL, and Brombacher F. Differential Requirements for IL-4 and IL-13 in Protein Contact Dermatitis Induced by Anisakis. Allergy. Feb 2009. 

Khodoun M, Strait R, Orekov T, Hogan S, Karasuyama H, Herbert DR, Köhl J, Finkelman FD. Peanuts can contribute to anaphylactic shock by activating complement. J Allergy Clin Immunol. 2009 Feb;123(2):342-51

Herbert DR, Orekov T, Perkins C, Finkelman FD. IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis. J Immunol. 2008 Nov 15;181(10):7214-20.

Herbert DR, Orekov T, Perkins C, Rothenberg ME, Finkelman FD. IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis. J Immunol. 2008 Apr 1;180(7):4948-55.

Herbert DR, Orekov T, Perkins C, Rothenburg ME and Finkelman FD. Redundancy Between Interleukin 10 and Transforming Growth Factor Beta Limits Immunopathology and Prevents Mortality During Murine Schistosomiasis. Journal of Immunology. Nov Vol#181, No. 10, pp. 7214-20, 2008.

Niewenhuizen N, Herbert DR, Lopata A and Brombacher F. CD4 T-cell Specific Deletion of IL-4 Receptor Alpha Prevents OVA-Induced Anaphylaxis by an IFN-y Dependent Mechanism. Journal of Immunology. Sep Vol# 179, pp. 2758-2765, 2007.

Clinical Interests

Asthma; allergic rhinitis; food allergy; urticaria

Research Interests

Genetics of allergy and asthma; cytokines; signaling pathways

Le Cras TD, Acciani TH, Mushaben EM, Kramer EL, Pastura PA, Hardie WD, Korfhagen TR, Sivaprasad U, Ericksen M, Gibson AM, Holtzman MJ, Whitsett JA, Khurana Hershey GK. Epithelial EGF receptor signaling mediates airway hyperreactivity and remodeling in a mouse model of chronic asthma. Am J Physiol Lung Cell Mol Physiol. 2011 Mar;300(3):L414-21.

Baye TM, Butsch Kovacic M, Biagini Myers JM, Martin LJ, Lindsey M, Patterson TL, He H, Ericksen MB, Gupta J, Tsoras AM, Lindsley A, Rothenberg ME, Wills-Karp M, Eissa NT, Borish L, Khurana Hershey GK. Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children. PLoS One. 2011 Feb 28;6(2):e16522.

Cortina SD, Drotar D, Ericksen M, Lindsey M, Patterson TL, Biagini Myers JM, Kovacic MB, Khurana Hershey GK. Genetic Biomarkers of Health-Related Quality of Life in Pediatric Asthma. J Pediatr. 2011 Feb 14.

Epstein TG, Bernstein DI, Levin L, Khurana Hershey GK, Ryan PH, Reponen T, Villareal M, Lockey JE, Lemasters GK. Opposing effects of cat and dog ownership and allergic sensitization on eczema in an atopic birth cohort. J Pediatr. 2011 Feb;158(2):265-271.e5.

Newcomb DC, Boswell MG, Zhou W, Huckabee MM, Goleniewska K, Sevin CM, Khurana Hershey GK, Kolls JK, Peebles RS Jr. Human T(H)17 cells express a functional IL-13 receptor and IL-13 attenuates IL-17A production. J Allergy Clin Immunol. 2011 Jan 12.

Sivaprasad U, Askew DJ, Ericksen MB, Gibson AM, Stier MT, Brandt EB, Bass SA, Daines MO, Chakir J, Stringer KF, Wert SE, Whitsett JA, Le Cras TD, Wills-Karp M, Silverman GA, Khurana Hershey GK. A nonredundant role for mouse Serpinb3a in the induction of mucus production in asthma. J Allergy Clin Immunol. 2011 Jan;127(1):254-61, 261.e1-6.

Sivaprasad U, Warrier MR, Gibson AM, Chen W, Tabata Y, Bass SA, Rothenberg ME, Khurana Hershey GK. IL-13Rα2 has a protective role in a mouse model of cutaneous inflammation. J Immunol. 2010 Dec 1;185(11):6802-8.

Biagini Myers JM, Khurana Hershey GK. Eczema in early life: genetics, the skin barrier, and lessons learned from birth cohort studies.J Pediatr. 2010 Nov;157(5):704-14.

Baye TM, Martin LJ, Khurana Hershey GK. Application of genetic/genomic approaches to allergic disorders. J Allergy Clin Immunol. 2010 Sep;126(3):425-36; quiz 437-8.

Codispoti CD, Levin L, LeMasters GK, Ryan P, Reponen T, Villareal M, Burkle J, Stanforth S, Lockey JE, Khurana Hershey GK, Bernstein DI. Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis. J Allergy Clin Immunol. 2010 May;125(5):1054-1060.e1.

Allergies; food allergies; eosinophil biology; gastrointestinal inflammation

Visit the Hogan Lab.

Munitz A, Cole ET, Beichler A, Groschwitz K, Ahrens R, Steinbrecher K, Willson T, Han X, Denson L, Rothenberg ME, Hogan SP. Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis. Gastroenterology. 2010 Aug;139(2):530-41.

Osterfeld H, Ahrens R, Strait R, Finkelman FD, Renauld JC, Hogan SP. Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis. J Allergy Clin Immunol. 2010 Feb;125(2):469-476.e2.

Finkelman FD, Hogan SP, Hershey GK, Rothenberg ME, Wills-Karp M. Importance of cytokines in murine allergic airway disease and human asthma. J Immunol. 2010 Feb 15;184(4):1663-74. Review.

Groschwitz KR, Ahrens R, Osterfeld H, Gurish MF, Han X, Abrink M, Finkelman FD, Pejler G, Hogan SP. Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22381-6.

Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF Jr, Rothenberg ME, Finkelman FD. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med. 2009 Dec 21;206(13):2947-57.

Groschwitz KR, Hogan SP. Intestinal barrier function: molecular regulation and disease pathogenesis. J Allergy Clin Immunol. 2009 Jul;124(1):3-20; quiz 21-2. Review.

Munitz A, Seidu L, Cole ET, Ahrens R, Hogan SP, Rothenberg ME. Resistin-like molecule alpha decreases glucose tolerance during intestinal inflammation. J Immunol. 2009 Feb 15;182(4):2357-63.

Hogan SP. Functional role of eosinophils in gastrointestinal inflammation. Immunol AllergyClin North Am. 2009 Feb;29(1):129-40, xi. Review.

Munitz A, Waddell A, Seidu L, Cole ET, Ahrens R, Hogan SP, Rothenberg ME. Resistin-like molecule alpha enhances myeloid cell activation and promotes colitis. J Allergy Clin Immunol. 2008 Dec;122(6):1200-1207.e1.

Ahrens R, Waddell A, Seidu L, Blanchard C, Carey R, Forbes E, Lampinen M, Wilson T, Cohen E, Stringer K, Ballard E, Munitz A, Xu H, Lee N, Lee JJ, Rothenberg ME, Denson L, Hogan SP. Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis. J Immunol. 2008 Nov 15;181(10):7390-9.

Clinical Interests

Periodic fever with aphthous stomatitis; Pharangytis and Cervical Adenitis Syndrome (PFAPA); treatment and prevention of asthma; allergic rhinitis; eczema; food allergy; anaphylaxis; suspected immune deficiency

Research Interests

Role of environmental allergen and pollutants in childhood asthma; asthma pathogenisis and treatment; inflammatory processes in Pharangytis and Cervical Adenitis Syndrome (PFAPA); response of PFAPA to treatment with Singulair (montelukast)

Spanier AJ, Kahn RS, Hornung RW, Wang N, Sun G, Lierl MB, Lanphear BP. Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in asthmatic children.Pediatr Pulmonol. 2009 Aug;44(8):812-9.

Spanier AJ, Hornung RW, Kahn RS, Lierl MB, Lanphear BP. Seasonal variation and environmental predictors of exhaled nitric oxide in children with asthma.Pediatr Pulmonol. 2008 Jun;43(6):576-83.

Lierl M. Periodic fever syndromes: a diagnostic challenge for the allergist.Allergy. 2007 Dec;62(12):1349-58. Review.

Spanier AJ, Hornung R, Lierl M, Lanphear BP. Environmental exposures and exhaled nitric oxide in children with asthma.J Pediatr. 2006 Aug;149(2):220-6.

Lierl MB, Hornung RW. Relationship of outdoor air quality to pediatric asthma exacerbations. Ann Allergy Asthma Immunol. 2003 Jan;90(1):28-33.

Lierl MB. Isolated late cutaneous reactions to allergen skin testing in children. Ann Allergy Asthma Immunol. 2000 Mar;84(3):294-8.

Assa'ad A, Lierl M. Effect of acellular pertussis vaccine on the development of allergic sensitization to environmental allergens in adults.J Allergy Clin Immunol. 2000 Jan;105(1 Pt 1):170-5.

Alibrahim A, Lepore M, Lierl M, Filipovich A, Assaád A. Pneumocystis carinii pneumonia in an infant with X-linked agammaglobulinemia.J Allergy Clin Immunol. 1998 Apr;101(4 Pt 1):552-3.

Assa'ad AH, Ballard ET, Sebastian KD, Loven DP, Boivin GP, Lierl MB. Effect of superoxide dismutase on a rabbit model of chronic allergic asthma. Ann Allergy Asthma Immunol. 1998 Mar;80(3):215-24.

Yassin MS, Lierl MB, Fischer TJ, O'Brien K, Cross J, Steinmetz C. Latex allergy in hospital employees.Ann Allergy. 1994 Mar;72(3):245-9.

Pulmonary and esophageal inflammationl; eosinophilic esophagitis; aeroallergen-induced allergic responses in the lung and gastrointestinal tract

Rayapudi M, Mavi P, Zhu X, Pandey AK, Abonia JP, Rothenberg ME, Mishra A. Indoor insect allergens are potent inducers of experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2010 Aug;88(2):337-46.

Zhu X, Wang M, Mavi P, Rayapudi M, Pandey AK, Kaul A, Putnam PE, Rothenberg ME, Mishra A. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology. 2010 Jul;139(1):182-93.e7.

Zhu X, Wang M, Crump CH, Mishra A. An imbalance of esophageal effector and regulatory T cell subsets in experimental eosinophilic esophagitis in mice. Am J Physiol Gastrointest Liver Physiol. 2009 Sep;297(3):G550-8.

Mishra A. Mechanism of eosinophilic esophagitis. Immunol Allergy Clin North Am. 2009 Feb;29(1):29-40, viii. Review.

Palumbo JS, Barney KA, Blevins EA, Shaw MA, Mishra A, Flick MJ, Kombrinck KW, Talmage KE, Souri M, Ichinose A, Degen JL. Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function. J Thromb Haemost. 2008 May;6(5):812-9.

Mishra A, Wang M, Pemmaraju VR, Collins MH, Fulkerson PC, Abonia JP, Blanchard C, Putnam PE, Rothenberg ME. Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology. 2008 Jan;134(1):204-14.

Mishra A, Wang M, Schlotman J, Nikolaidis NM, DeBrosse CW, Karow ML, Rothenberg ME. Resistin-like molecule-beta is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung. Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L305-13.

Mishra A, Schlotman J, Wang M, Rothenberg ME. Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice. J Leukoc Biol. 2007 Apr;81(4):916-24.

Hogan SP, Seidu L, Blanchard C, Groschwitz K, Mishra A, Karow ML, Ahrens R, Artis D, Murphy AJ, Valenzuela DM, Yancopoulos GD, Rothenberg ME. Resistin-like molecule beta regulates innate colonic function: barrier integrity and inflammation susceptibility. J Allergy Clin Immunol. 2006 Jul;118(1):257-68.

Akei HS, Brandt EB, Mishra A, Strait RT, Finkelman FD, Warrier MR, Hershey GK, Blanchard C, Rothenberg ME. Epicutaneous aeroallergen exposure induces systemic TH2 immunity that predisposes to allergic nasal responses. J Allergy Clin Immunol. 2006 Jul;118(1):62-9.

Inhibitory receptors; eosinophils; asthma; eosinophilic esophagitis

Munitz A, Cole ET, Beichler A, Groschwitz K, Ahrens R, Steinbrecher K, Willson T, Han X, Denson L, Rothenberg ME, Hogan SP. Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis.Gastroenterology. 2010 Aug;139(2):530-41. Epub 2010 Apr 14.

Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF Jr, Rothenberg ME, Finkelman FD. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection.J Exp Med. 2009 Dec 21;206(13):2947-57.

Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.J Immunol. 2009 Apr 15;182(8):4994-5002.

Munitz A, Seidu L, Cole ET, Ahrens R, Hogan SP, Rothenberg ME. Resistin-like molecule alpha decreases glucose tolerance during intestinal inflammation.J Immunol. 2009 Feb 15;182(4):2357-63.

Munitz A, Waddell A, Seidu L, Cole ET, Ahrens R, Hogan SP, Rothenberg ME. Resistin-like molecule alpha enhances myeloid cell activation and promotes colitis.J Allergy Clin Immunol. 2008 Dec;122(6):1200-1207.e1.

Brandt EB, Munitz A, Orekov T, Mingler MK, McBride M, Finkelman FD, Rothenberg ME. Targeting IL-4/IL-13 signaling to alleviate oral allergen-induced diarrhea. J Allergy Clin Immunol. 2009 Jan;123(1):53-8.

Ahrens R, Waddell A, Seidu L, Blanchard C, Carey R, Forbes E, Lampinen M, Wilson T, Cohen E, Stringer K, Ballard E, Munitz A, Xu H, Lee N, Lee JJ, Rothenberg ME, Denson L, Hogan SP. Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis.J Immunol. 2008 Nov 15;181(10):7390-9.

Munitz A, Brandt EB, Mingler M, Finkelman FD, Rothenberg ME. Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis. Proc Natl Acad Sci U S A. 2008 May 20;105(20):7240-5.

Munitz A, McBride ML, Bernstein JS, Rothenberg ME. A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils. Blood. 2008 Jun 15;111(12):5694-703.

Clinical Interests

Immune deficiency; immune dysregulation

Research Interests

Pathophysiology of perforin missense mutations identified in individuals with hemophagocytic lymphohistiocytosis; Molecular mechanisms of primary immune deficiency and dysregulation; Natural killer cell and cytotoxic T lymphocyte cytotoxicity

MD: Case Western Reserve University School of Medicine, Cleveland, OH, 1997.

PhD: Case Western Reserve University School of Medicine, Cleveland, OH, 1996.

Residency: Pediatrics, Cincinnati Children's Hospital Medical Center, 1997-2000.

Fellowship: Allergy / Immunology, Cincinnati Children's Hospital Medical Center.

Certification: Pediatrics, 2007; Allergy and Immunology, 2005.

Sumegi J, Barnes MG, Nestheide SV, Molleran-Lee S, Villanueva J, Zhang K, Risma KA, Grom AA, Filipovich AH. Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis. Blood. 2011 Apr 14;117(15):e151-60.

Uygungil B, Bleesing JJ, Risma KA, McNeal MM, Rothenberg ME. Persistent rotavirus vaccine shedding in a new case of severe combined immunodeficiency: A reason to screen. J Allergy Clin Immunol. 2010 Jan;125(1):270-1.

Marsh RA, Villanueva J, Kim MO, Zhang K, Marmer D, Risma KA, Jordan MB, Bleesing JJ, Filipovich AH. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009 Jul;132(1):116-23.

Marsh RA, Villanueva J, Zhang K, Snow AL, Su HC, Madden L, Mody R, Kitchen B, Marmer D, Jordan MB, Risma KA, Filipovich AH, Bleesing JJ. A rapid flow cytometric screening test for X-linked lymphoproliferative disease due to XIAP deficiency. Cytometry B Clin Cytom. 2009 Sep;76(5):334-44.

Urrea Moreno R, Gil J, Rodriguez-Sainz C, Cela E, LaFay V, Oloizia B, Herr AB, Sumegi J, Jordan MB, Risma KA. Functional assessment of perforin C2 domain mutations illustrates the critical role for calcium-dependent lipid binding in perforin cytotoxic function. Blood. 2009 Jan 8;113(2):338-46.

Zhang K, Johnson JA, Biroschak J, Villanueva J, Lee SM, Bleesing JJ, Risma KA, Wenstrup RJ, Filipovich AH. Familial haemophagocytic lymphohistiocytosis in patients who are heterozygous for the A91V perforin variation is often associated with other genetic defects. Int J Immunogenet. 2007 Aug;34(4):231-3.

Thomas H, Risma KA, Graham TB, Brody AS, Deutsch GH, Young LR, Joseph PM. A kindred of children with interstitial lung disease. Chest. 2007 Jul;132(1):221-30.

Bullock JZ, Villanueva JM, Blanchard C, Filipovich AH, Putnam PE, Collins MH, Risma KA, Akers RM, Kirby CL, Buckmeier BK, Assa'ad AH, Hogan SP, Rothenberg ME. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007 Jul;45(1):22-31.

Risma KA, Frayer RW, Filipovich AH, Sumegi J. Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis. J Clin Invest. 2006 Jan;116(1):182-92.

Clinical Interests

Eosinophilia; eosinophilic disorders; asthma; allergy; food allergy

Research Interests

Eosinophils; chemokines

Visit the Rothenberg Lab.

MD, PhD: Harvard Medical School, Cambridge, MA, 1990.

Residency: Pediatrics, Children's Hospital, Boston, MA, 1991-1992.

Fellowship: Immunology / Allergy, Children's Hospital, Boston, MA, 1992-1994; Hematology / Oncology, Children's Hospital and Dana Farber Cancer Institute, Boston, MA, 1992-1995.

Certification: National Board of Medical Examiners, 1991; Board of Registration in Medicine, MA, 1992; American Board of Pediatrics, 1995, 2001, 2008; Ohio State Medical Board, 1997; American Board of Allergy and Immunology, 1997, 2006.

Franciosi JP, Hommel KA, Debrosse CW, Greenberg AB, Greenler AJ, Abonia JP, Rothenberg ME, Varni JW. Quality of life in paediatric eosinophilic oesophagitis: what is important to patients? Child Care Health Dev. 2011.

Debrosse CW, Franciosi JP, King EC, Buckmeier Butz BK, Greenberg AB, Collins MH, Abonia JP, Assa'ad A, Putnam PE, Rothenberg ME. Long-term outcomes in pediatric-onset esophageal eosinophilia. J Allergy Clin Immunol. 2011.

Sherrill JD, Rothenberg ME. Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies. J Allergy Clin Immunol. 2011.

Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, Burks AW, Chehade M, Collins MH, Dellon ES, Dohil R, Falk GW, Gonsalves N, Gupta SK, Katzka DA, Lucendo AJ, Markowitz JE, Noel RJ, Odze RD, Putnam PE, Richter JE, Romero Y, Ruchelli E, Sampson HA, Schoepfer A, Shaheen NJ, Sicherer SH, Spechler S, Spergel JM, Straumann A, Wershil BK, Rothenberg ME, Aceves SS. Eosinophilic esophagitis: Updated consensus recommendations for children and adults. J Allergy Clin Immunol. 2011.

Baye TM, Butsch Kovacic M, Biagini Myers JM, Martin LJ, Lindsey M, Patterson TL, He H, Ericksen MB, Gupta J, Tsoras AM, Lindsley A, Rothenberg ME, Wills-Karp M, Eissa NT, Borish L, Khurana Hershey GK. Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children. PLoS One. 2011 Feb 28;6(2):e16522.

Blanchard C, Stucke EM, Rodriguez-Jimenez B, Burwinkel K, Collins MH, Ahrens A, Alexander ES, Butz BK, Jameson SC, Kaul A, Franciosi JP, Kushner JP, Putnam PE, Abonia JP, Rothenberg ME. A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol. 2011 Jan;127(1):208-17, 217.e1-7.

Zhu H, Perkins C, Mingler MK, Finkelman FD, Rothenberg ME. The role of neuropeptide S and neuropeptide S receptor 1 in regulation of respiratory function in mice. Peptides. 2011 Apr;32(4):818-25.

Sivaprasad U, Warrier MR, Gibson AM, Chen W, Tabata Y, Bass SA, Rothenberg ME, Khurana Hershey GK. IL-13Rα2 has a protective role in a mouse model of cutaneous inflammation. J Immunol. 2010 Dec 1;185(11):6802-8.

Miles MV, Putnam PE, Miles L, Tang PH, DeGrauw AJ, Wong BL, Horn PS, Foote HL, Rothenberg ME. Acquired coenzyme Q10 deficiency in children with recurrent food intolerance and allergies. Mitochondrion. 2011 Jan;11(1):127-35.

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. 2011;156(2):137-147. 

von Tiehl KF, Stevenson DD, Oldstone MBA. Cytokine Profiles in Aspirin-exacerbated Respiratory Disease Support the Theory of a Chronic Viral Infection. Ann Allergy Asthma Immunol. 2009.

von Tiehl KF, Stevenson DD. A Case of Hydroxyurea-responsive, Non-aspirin-sensitive, Treatment-refractory, Severe, Eosinophilic Nasal Polyposis, Chronic Rhinosinusitis and Asthma. Ann Allergy Asthma Immunol. 2008.

von Tiehl KF, Woessner KM, Simon RA, Stevenson DD. Characterization of Oral Aspirin Challenge-induced Extra-respiratory Reactions in Patients Suspected of Having Aspirin-exacerbated Respiratory Disease. J Allergy Clin Immunol. 2008;121(2):S194.

von Tiehl KF, Price MJ, Valencia R, Ludington KJ, Teirstein PS, Simon RA. Clopidogrel desensitization after drug-eluting stent placement. J Am Coll Cardiol. 2007 Nov 20;50(21):2039-43. 

Wang YH, Voo KS, Liu B, Chen CY, Uygungil B, Spoede W, Bernstein JA, Huston DP, Liu YJ. A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med. 2010 Oct 25;207(11):2479-91.

Shaw J, Wang YH, Ito T, Arima K, Liu YJ. Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70. Blood. 2010 Apr 15;115(15):3051-7.

Wang YH, Liu YJ. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin Exp Allergy. 2009 Jun;39(6):798-806. 

Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4793-8.

Lu N, Wang YH, Wang YH, Arima K, Hanabuchi S, Liu YJ. TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis. J Exp Med. 2009 Sep 28;206(10):2111-9.

Esashi E, Wang YH, Perng OA, Qin XF, Hennighausen L, Liu YJ, Watowich SS. Differential regulation of plasmacytoid and conventional dendritic cell development by GM-CSF through STAT5. Immunity. 2008;28:1-12.

Wang YH, Liu YJ. The IL-17 cytokine family and their role in allergic inflammation. Curr Opin Immunol. 2008 Dec;20(6):697-702.

Wang YH, Liu YJ. OX40-OX40L interactions: a promising therapeutic target for allergic diseases?J Clin Invest. 2007 Dec;117(12):3655-7. 

Wang YH, Angkasekwinai P, Meng Q, Lu N, Voo KS, Arima K, Hanabuchi S, Corrigan CG, Lee T, Dong C, Huston DR, Yao Z,  Ying S, and Liu YJ. IL-25 mediated cross talk between eosinophils and TSLP-DC-activated TH2 memory cells augments allergic immune responses. J. Exp. Med. 2007;204(8): 1837-1847. 

 Ito T, Wang YH, Duramad O, Hanabuchi S, Perng OA, Gilliet M, Qin FX, Liu YJ. OX40 ligand shuts down IL-10-producing regulatory T cells. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13138-43. 

Asthma; allergy; eosinophils; lung inflammation

Visit the Zimermann Lab.

Niese KA, Collier AR, Hajek AR, Cederbaum SD, O'Brien WE, Wills-Karp M, Rothenberg ME and 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. 2009;10:33.

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. 2009; 14(13):2774-82.

Zimmermann N, McBride ML, Yamada Y, Hudson SA, Jones C, Cromie KD, Crocker PR, Rothenberg ME, Bochner BS. Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils. Allergy. 2008;63:1156-63.

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. 2007;119:391-7.

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. 2007;19:54-59.

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 the intestine. Clin Exp Allergy. 2006; 36(4):543-53.

Zimmermann N, Rothenberg ME. The arginine-arginase balance in asthma and lung inflammation. Eur J Pharmacol. 2006;533(1-3):253-62

Rothenberg ME, Doepker MP, Lewkowich IP, Chiaramonte MG, Stringer KF, Finkelman FD, MacLeod CL, Ellies LG and Zimmermann N. The cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung. Proc Natl Acad Sci USA. 2006;103:14895

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. 2006;177:5595-603.

Fulkerson PC, Zhu H, Williams DA, Zimmermann N, Rothenberg ME. CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism. Blood. 2005;106(2):436-43.

Clinical Interests

Food allergy; eosinophilic esophagitis; asthma

Research Interests

Mechanism and the new therapeutic options for food allergy, including eosinophilic esophagitis
 

MD: Zunyi Medical College, Guizhou, China, 1982.

Residency: Pediatrics, University of Toledo Medical Center, Toledo, Ohio, 2005.

Fellowship: Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 2007.

Certifications: American Board of Pediatrics, American Board of Allergy and Immunology, 2011.

Zuo L, Fulkerson PC, Finkelman FD, Mingler M, Fischetti CA, Blanchard C, Rothenberg ME. IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway. J Immunol. 2010 Jul 1;185(1):660-9.

Zuo L, Rothenberg ME. Eosinophil Associated Gastrointestinal Disorders (EGID). Clinical Immunology. 2008;46:691-700.

Zuo L, Rothenberg ME. Gastrointestinal eosinophilia. Immunol Allergy Clin North Am. 2007 Aug;27(3):443-55. Review.

Book Chapters

DeBrosse CW, Zuo L. Eosinophilic Enteritis. In Stefano Guandalini and Haleh Vaziri (eds): Diarrhea: Diagnostic and Therapeutic Advances. Humana Express: New York, NY, 2010.