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Our research spans fundamental studies, translational investigation and clinical trials. Novel models of immunological diseases, developed and/or fine-tuned by divisional researchers, provide unprecedented systems to investigate key inflammatory steps involved in pediatric allergic and immunological disease and to enhance our understanding of mast cells, eosinophils, macrophages and lymphocytes. Our integrative laboratories are led by nationally recognized researchers and employ state-of-the-art model systems for genetic, biochemical, immunological and physiological analysis.
Read more about our faculty's research below.
Marc E. Rothenberg, MD, PhD Director, Division of Allergy and Immunology
is focused on elucidating mechanisms of allergic responses, especially in mucosal tissues such as the lung and the gastrointestinal tract, in order to identify novel pharmaceutical targets for treatment of patients with eosinophilic diseases including eosinophilic gastrointestinal disorders, hypereosinophilic syndromes and asthma and food allergies. Lab has identified and characterized several critical pathways that regulate allergic responses.
Visit the Rothenberg Lab web site.
Director, Division of Allergy and Immunology
Director, Cincinnati Center for Eosinophilic Disorders
Professor, UC Department of Pediatrics
Eosinophilia; eosinophilic disorders; asthma; allergy; food allergy
Dr. Rothenberg is director of the Division of Allergy/Immunology at Cincinnati Children's Hospital Medical Center and tenured professor of pediatrics at Cincinnati Children’s and University of Cincinnati College of Medicine. He graduated summa cum laude with highest honors in chemistry and biochemistry from Brandeis University. He then completed the MD/PhD program at Harvard Medical School under Dr. Frank Austen, conducting studies on eosinophil hematopoiesis, as he developed the first culture system for human eosinophils. After completing residency at Children’s Hospital, Boston, Dr. Rothenberg did a fellowship in allergy/immunology and hematology at Children’s Hospital. Dr. Rothenberg did post-doctorate training with Dr. Philip Leder, Harvard Medical School, where he cloned the eotaxin chemokine. After being faculty at Harvard Medical School for one year, he came to the University of Cincinnati and Cincinnati Children's, where he has helped build a top program in research, and his division is a leader in allergy and immunology.
His research is focused on molecular analysis of allergic inflammation, primarily on the molecular pathogenesis of eosinophilic esophagitis. His laboratory takes a multi-disciplinary approach including the development of preclinical murine models: genetics, genomics, molecular immunology, and biochemistry. Dr. Rothenberg’s awards include the 2007 E Mead Johnson Award from the Society of Pediatric Research, 2010 National Institutes of Health MERIT Award, and being elected an American Association for the Advancement of Science fellow. He is a member of the American Society for Clinical Investigation, American Academy of Pediatrics, and Society for Pediatric Radiology. His publications number over 300. He has served on review panels for journals/grant agencies including National Institutes of Health (NIH), Burroughs Trust, and Medical Research Council of the United Kingdom. He served for four-years on the Advisory Council of National Institute of Allergy and Infectious Disease. He has been associate editor of the Journal of Allergy and Clinical Immunology since 2004. His research has been supported by sources including the NIH, Human Frontier Science Program Organization, Burroughs Wellcome Fund, Dana Foundation, and Department of Defense.
Visit the Rothenberg Lab web site.
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.
Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014 Aug;147(2):324:33.e5.
Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM, Stucke EM, Kemme KA, Costello MS, Mingler MK, Blanchard C, Collins MH, Abonia JP, Putnam PE, Dellon ES, Orlando RC, Hogan SP, Rothenberg ME. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014 May;7(3):718-29.
Wen T, Stucke EM, Grotjan TM, Kemme KA, Abonia JP, Putnam PE, Franciosi JP, Garza JM, Kaul A, King EC, Collins MH, Kushner JP, Rothenberg ME. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology. 2013 Dec;145(6):1289-99.
Wen T, Besse JA, Mingler MK, Fulkerson PC, Rothenberg ME. Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil trafficking in vivo. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6067-72.
Lu TX, Sherrill JD, Wen T, Plassard AJ, Besse JA, Abonia JP, Franciosi JP, Putnam PE, Eby M, Martin LJ, Aronow BJ, Rothenberg ME. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2012 Apr;129(4):1064-75.e9.
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.
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 HEC Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28.
Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa'ad AH, Putnam PE, Aronow BJ, Rothenberg ME. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006 Feb;116(2):536-47.
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. 2001 Apr;2(4):353-60.
Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001 Jan;107(1):83-90.
NICHHD Pediatric Center for Gene Expression and Developmental Sciences. Training Director. National Institutes of Health. Dec 2011–Nov 2016. K12 HD028827.
Epithelial Genes in Allergic Inflammation. Co-Investigator. National Institutes of Health. Sep 2011–Aug 2016. U19 AI070235.
Eosinophil:M2 Macrophage:CCL11 Axis in Experimental Colitis and Pediatric Corticosteroid Resistant Ulcerative Colitis. Co-Investigator. National Institutes of Health. Apr 2012–Mar 2016. R01 DK090119-01A1.
The Expression and Function of Paired Immunoglobulin-like Receptor B in Eosinophils. Co-Principal Investigator. U.S. - Israel Binational Science Foundation. Oct 2012–Sep 2016. #201144.
J. Pablo Abonia, MD Interim Director, Registry for Eosinophilic Disorders (REGID)
Interim Director, Registry for Eosinophilic Disorders (REGID)
Associate Professor, UC Department of Pediatrics
Eosinophilic and mast cell disorders; immunodeficiency
J. Pablo Abonia, MD, provides the bulk of the clinical allergy care for patients with eosinophilic disease. He is currently involved in a multicenter clinical research trial of anti-IL5 (reslizumab) for patients with eosinophilic esophagitis. His research focuses on mining the research databanks (patient characteristics, tissue samples, RNA and DNA) to elucidate the mechanisms, diagnosis and treatment of eosinophilic esophagitis, and he is the interim director of the Registry for Eosinophilic Disorders (REGID). He is particularly interested in the role of mast cells in eosinophilic esophagitis.
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, Rothenberg ME. Eosinophilic esophagitis: rapidly advancing insights. Annu Rev Med. 2012;63:421-34.
Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G 3rd, O'Gorman MA, Abonia JP, Young J, Henkel T, Wilkins HJ, Liacouras CA. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012 Feb;129(2):456-63.
Lu TX, Sherrill JD, Wen T, Plassard AJ, Besse JA, Abonia JP, Franciosi JP, Putnam PE, Eby M, Martin LJ, Aronow BJ, Rothenberg ME. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2012 Apr;129(4):1064-75.
Henderson CJ, Abonia JP, King EC, Putnam PE, Collins MH, Franciosi JP, Rothenberg ME. Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis.J Allergy Clin Immunol. 2012 Jun;129(6):1570-8.
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. 2012 Jul;38(4):477-83.
Franciosi JP, Hommel KA, Greenberg AB, Debrosse CW, Greenler AJ, Abonia JP, Rothenberg ME, Varni JW. Development of the Pediatric Quality of Life Inventory Eosinophilic Esophagitis Module items: qualitative methods. BMC Gastroenterol. 2012 Sep 25;12(1):135.
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.Abonia JP, Castells M. Drug allergy in pediatric patients. Pediatr Ann. 2011 Apr;40(4):200-4.
Franciosi JP, Hommel KA, DeBrosse CW, Greenberg AB, Greenler AJ, Abonia JP, Rothenberg ME, Varni JW. Development of a validated patient-reported symptom metric for pediatric eosinophilic esophagitis: qualitative methods. BMC Gastroenterol. 2011 Nov 18;11:126.
Amal H. Assa'ad, MD Associate Director, Division of Allergy and Immunology
centers her research on food allergy and asthma. She has established a food allergy research to study the optimal diagnosis for food allergies and reactions and potential treatments, including desensitization protocols. Dr. Assa’ad conducts clinical trials using novel biologic agents for the treatment of eosinophilic disorders, including those of the gastrointestinal tract, and for the treatment of severe asthma in pediatric and adult patients.
Associate Director, Division of Allergy and Immunology
Director of Clinical Services, Division of Allergy and Immunology
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.
Amin MR, Khoury JC, Assa’ad AH. Food-specific serum immunoglobulin E measurements in children presenting with food allergy. Ann Allergy Asthma Immunol. 2014; 112(2): 121-5.
Fiocchi A, Annunziato F, Assa'ad A, et al. The management of paediatric allergy: not everybody's cup of tea--10-11th February 2012. Curr Opin Allergy Clin Immunol, 2013; 13 Suppl 1, S1-50.
Fleischer D, Spergel J, Assa’ad A, Pongracic J. Primary Prevention of Allergic Disease Through Nutritional Interventions. J Allergy Clin Immunol. In Practice, 2013; 1(1): 29-36.
Assa'ad A, Fiocchi A. Guidelines change the diagnostic process of cow milk food allergy: problem- based learning. Curr Opin Allergy Clin Immunol. 2012; 12:564–569.
Butsch Kovacic M, Biagini Myers JM, Lindsey M, Patterson T, Sauter S, Ericksen MB, Ryan P, Assa'ad A, et al. The Greater Cincinnati Pediatric Clinic Repository: A Novel Framework for Childhood Asthma and Allergy Research. Pediatr Allergy Immunol Pulmonol. 2012; 25(2): 104-113.
Uygungil B, Assa'ad A, et al. Immunodeficiency: a problem with the faucet or the drain?Ann Allergy Asthma Immunol. 2011; 107(6): p. 547-9.
Sackesen C, Assa'ad A, et al. Cow's milk allergy as a global challenge. Curr Opin Allergy Clin Immunol. 2011(3): 243-248.
Burks AW, Jones SM, Boyce JA, Sicherer SH, Wood RA, Assa'ad A, Sampson HA. NIAID-Sponsored 2010 Guidelines for Managing Food Allergy: Applications in the Pediatric Population. Pediatrics. 2011; 128(5): 955-965.
Boyce JA, Assa'ad A, et al. Guidelines for the diagnosis and management of food allergy in the United States: summary of the NIAID-sponsored expert panel report. Nutr Res. 2011; 31(1): 61-75.
Assa'ad AH, Gupta SK, Collins MH, et al. An Antibody Against IL-5 Reduces Numbers of Esophageal Intraepithelial Eosinophils in Children with Eosinophilic Esophagitis. Gastroenterology. 2011; 141(5): 1593-1604.
Artem Barski, PhD
Assistant Professor, UC Department of Pediatrics
Epigenetics; epigenomics; immunology; T cell memory
Visit the Barski Lab
Artem Barski, PhD, is interested in epigenetic and transcriptional regulation of gene expression. During his post-doctoral training in Keji Zhao lab at NIH, Dr. Barski took part in the development of ChIP-Seq, a revolutionary method that combines ChIP with the next-generation sequencing. ChIP-Seq allows genome-wide mapping of chromatin modifications and transcription factor binding sites with resolution and sensitivity far exceeding older methods. Together with his NIH colleagues Dr. Barski used this approach to map more than 40 chromatin modifications in human T cells, which fundamentally improved the understanding of epigenetic regulation of transcription. Dr. Barski has since been using ChIP-Seq and other sequencing-based genome-wide methods to understand the role of chromatin modifications in gene regulation. His most recent work includes investigation of chromatin regulation of genes transcribed by RNA Polymerase III and the discovery of gene poising in T cells.
Since his arrival to Cincinnati Children’s Hospital Medical Center in 2011, Dr. Barski is utilizing ChIP-Seq, RNA-Seq and other cutting-edge approaches to understand epigenetic basis of T cell activation, memory and tolerance.
Barski A, Chepelev I, Liko D, Cuddapah S, Fleming AB, Birch J, Cui K, White RJ, Zhao K. Pol II and its associated epigenetic marks are present at Pol III-transcribed noncoding RNA genes. Nat Struct Mol Biol. 2010 May;17(5):629-34. Cuddapah S, Barski A, Zhao K. Epigenomics of T cell activation, differentiation, and memory. Curr Opin Immunol. 2010 Jun;22(3):341-7.
Cuddapah S, Barski A, Cui K, Schones DE, Wang Z, Wei G, Zhao K. Native chromatin preparation and Illumina/Solexa library construction. Cold Spring Harb Protoc. 2009 Jun;2009(6):pdb.prot5237. Barski A, Jothi R, Cuddapah S, Cui K, Roh TY, Schones DE, Zhao K. Chromatin poises miRNA- and protein-coding genes for expression. Genome Res. 2009 Oct;19(10):1742-51
Barski A, Zhao K. Genomic location analysis by ChIP-Seq. J Cell Biochem. 2009 May 1;107(1):11-8. Jothi R, Cuddapah S, Barski A, Cui K, Zhao K. Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data. Nucleic Acids Res. 2008 Sep;36(16):5221-31. Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008 Jul;40(7):897-903 Schones DE, Cui K, Cuddapah S, Roh TY, Barski A, Wang Z, Wei G, Zhao K. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008 Mar 7;132(5):887-98. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007 May 18;129(4):823-37. Barski A, Frenkel B. ChIP Display: novel method for identification of genomic targets of transcription factors. Nucleic Acids Res. 2004 Jul 13;32(12):e104.
Fred D. Finkelman, MD
uses mouse models to study the roles of antibodies and cytokines in health and disease. Particular interests include allergic disorders, parasitic worm infections, and antibody-mediated disorders.
Professor, UC Department of Internal Medicine
UC Department of Pediatrics
Internal medicine; rheumatology
Dr. Finkelman's group’s contributions to immunology and medicine have focused on the use of mouse models of normal and abnormal immune function. They have included the initial demonstrations that: 1) IL-4 is required for induction of IgE responses in vivo, IFN-γ promotes the induction of IgG2a responses in vivo, and IL-12 suppresses IgE responses in vivo; 2) IL-4, IL-13, IL-4Rα, and Stat6 are required for host protection against intestinal worms, and protect predominantly through effects on intestinal epithelial cells, including induction of RELMβ; 3) inflammatory stimuli are required to induce dendritic cells to present antigen in a stimulatory, rather than a tolerogenic fashion; 4) complement and macrophages are required for development of murine transfusion-related acute lung injury; 5) rapid desensitization with anti-FcεRIα monoclonal antibody is a safe and effective way to rapidly suppress IgE-mediated disorders; and 6) immunoglobulin isotypes that are relatively ineffective in the induction of antibody effector mechanisms protect against inflammatory disease.
In addition, his group has developed three important in vivo techniques: 1) the use of anti-IgD antibodies to stimulate polyclonal B cell and T cell activation and antibody secretion; 2) the use of cytokine/anti-cytokine monoclonal antibody complexes to induce long-lasting increases in cytokine effects; and 3) the in vivo cytokine capture assay for measurement of in vivo cytokine secretion.
BA: Queens College, Queens, NY, 1967.
MD: Yale University School of Medicine, New Haven, CN, 1971.
Residency: Internal Medicine, Yale-New Haven Hospital, New Haven, CN.
Fellowship: Laboratory of Immunology, NIAID, NIH, Bethesda, MD.
Fellowship: Rheumatology, University of Texas-Southwestern Medical School, Dallas, TX.
Certification: Internal Medicine, 1976; Rheumatology, 1980.
Strait RT, Posgai MT, Mahler A, Barasa N, Jacob CO, Köhl J, Ehlers M, Stringer K, Shanmukappa SK, Witte D, Hossain MM, Khodoun M, Herr AB, Finkelman FD. IgG1 protects against renal disease in a mouse model of cryoglobulinemia. Nature. 2014.
Khodoun M, Kucuk ZY, Strait RT, Krishnamurthy D, Janek K, Lewkowich IP, Morris SE, Finkelman FD. Rapid polyclonal desensitization with antibodies to IgE and FcεRIα. J Allergy Clin. Immunol. 2013 133(6):1555-64.
Strait RT, Hicks W, Barasa N, Mahler A, Khodoun M, Köhl J, Stringer K, Witte D, Van Rooijen N, Susskind BM, Finkelman FD. MHC class I-specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion related acute lung injury in mice. J Exp Med. 2011 208(12):2525-44.
Herbert, DR, Yang J-Q, 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 RELMβ protects against gastrointestinal worm infection. J Exp Med. 2009 206(13):2947-57.
Strait RT, Morris SC, Finkelman FD. IgG blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and FcγRIIb crosslinking. J Clin Invest. 2006 116(3):833-41.
Morris SC, Madden KB, Adamovicz JJ, Gause WC, Hubbard BR, Gately MK, Finkelman FD. Effects of Interleukin-12 on in vivo cytokine gene expression and Ig isotype selection. J Immunol. 1994 152(3):1047-56.
Urban JF Jr, Katona IM, Paul WE, Finkelman FD. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci. USA. 1991 88(13):5513-7.
Finkelman FD, Lees A, Birnbaum R, Gause WC, Morris SC. Dendritic cells can present antigen in vivo in a tolerogenic or an immunogenic fashion. J Immunol. 1996 157(4):1406-14.
Urban JF Jr, Noben-Trauth N, Donaldson DD, Madden KB, Morris SC, Collins M, Finkelman FD. IL-13, IL-4Rα, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity. 1998 8(2):255-64.
Finkelman FD, Katona IM, Mosmann TR, Coffman RL. Interferon-γ regulates the isotypes of immunoglobulin secreted during in vivo humoral immune responses. J Immunol. 1988 140(4):1022-7.
Suppression of established IgE-mediated disease. Principal Investigator. United States Veterans Authority. Apr 2012 - Mar 2016.
Induction of food allergy in mice by allergen inhalation. Principal Investigator. DoD. Jul 2013 - Jun 2016.
Rapid suppression of food allergy with anti-FceRIa antibody. Principal Investigator. Food Allergy Research and Education. Jun 2014 - May 2017.
Suppression of IgE-mediated disease by polyclonal rapid desensitization. Principal Investigator. National Institutes of Health/National Institute of Allergy and Infectious Diseases. Jul 2014 - Jun 2018. 1R01AI113162-01.
Patricia C. Fulkerson, MD, PhD
Eosinophilic disorders; immunodeficiency; immune dysregulation
Visit the Fulkerson Lab.
Patricia C. Fulkerson, MD, PhD, is an assistant professor of pediatrics at Cincinnati Children’s Hospital Medical Center within the University of Cincinnati College of Medicine. Her PhD under the mentorship of Dr. Marc Rothenberg was focused on the analysis of experimental allergic lung inflammation in mice. She made a series of groundbreaking observations including a novel approach to understanding the complex and coordinated interplay of the chemokine family of cytokines and eosinophils in experimental allergic lung disease. Throughout her graduate studies, Dr. Fulkerson was recognized as a top trainee in the laboratory. Nationally, she was selected for competitive awards; her most distinguished award was the Serono Ian Clark-Lewis Memorial Award, provided to a trainee for the best talk at the Keystone Symposium Chemokines & Chemokine Receptors. Locally, she has received several competitive awards and scholarships including the Physician Scientist Training Program Scholar Award, as well as prizes for participation in research forums. Upon completion of the MD/PhD program, Dr. Fulkerson completed a research-track pediatric residency. She was recognized as being an outstanding resident and was awarded the Thomas F. Boat Pediatric Pulmonology Award in her final year of residency.
Dr. Fulkerson's innovation and dedication to research continued to be recognized during her allergy/immunology fellowship; she received the AAI-Life Technologies Trainee Achievement Award from the American Association of Immunologists in 2011, and she has the distinction of having achieved extramural funding during her first year of clinical fellowship, with the NIH awarding her a K08 grant on her first application. This independent funding at such an early stage is a notable accomplishment. Now, as an assistant professor, Dr. Fulkerson’s independent research program is focused on the biology of the eosinophil lineage-committed progenitor (EoP). Her overall aim is to identify novel therapeutic targets to block eosinophil production for the treatment of patients with eosinophilic disorders. She has developed a number of innovative methods to study the regulation of eosinophil development including liquid culture systems to follow differentiation of both murine and human EoPs into mature effector eosinophils. The pathways that are identified in her culture systems are tested in models of hypereosinophilia, infection, and allergic inflammation to further characterize the clinical and therapeutic potential of candidate targets.
MD: Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH, 2007.
PhD: Molecular Genetics, Microbiology & Immunology, University of Cincinnati College of Medicine, Cincinnati, OH, 2005.
Residency: Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2010.
Fellowship: Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 2012.
Wechsler ME, Fulkerson PC, Bochner BS, Gauvreau GM, Gleich GJ, Henkel T, Kolbeck R, Mathur SK, Ortega H, Patel J, Prussin C, Renzi P, Rothenberg ME, Roufosse F, Simon D, Simon HU, Wardlaw A, Weller PF, Klion AD. Novel targeted therapies for eosinophilic disorders. J Allergy Clin Immunol. 2012;130(3):563-71.
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;185(1):660-9.
Fulkerson PC, Rothenberg ME. Origin, regulation and physiological function of intestinal eosinophils. Best Pract Res Clin Gastroenterol. 2008;22(3):411-23.
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;134(1):204-14.
Fulkerson PC, Fischetti CA, Rothenberg ME. Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling. Am J Pathol. 2006;169(6):2117-26.
Fulkerson PC, Fischetti CA, McBride ML, Hassman LM, Hogan SP, Rothenberg ME. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci U S A. 2006;103(44):16418-23.
Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa'ad AH, Putnam PE, Aronow BJ, Rothenberg ME. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006;116(2):536-47.
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.
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 U S A. 2004;101(7):1987-92.
Simon P. Hogan, PhD Director of Research, Division of Allergy and Immunology
Director of Research, Division of Allergy and Immunology
Director of Admissions, Immunology Graduate Program
Food allergies and anaphylaxis; inflammatory bowel diseases (IBD); innate immunity; gastrointestinal immunity and function; cystic fibrosis (CF)
Visit the Hogan Lab.
BSC: Australian National University, Canberra, Australia, 1998.
PhD: John Curtin School of Medical Research, Australian National University, Canberra, Australia, 1998.
Lampinen M, Waddell A, Ahrens R, Carlson M, Hogan SP. CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis. J Leukoc Biol. 2013 Nov;94(5):1061-70.
Waddell A, Ahrens R, Tsai YT, Sherrill JD, Denson LA, Steinbrecher KA, Hogan SP. Intestinal CCL11 and eosinophilic inflammation is regulated by myeloid cell-specific RelA/p65 in mice. J Immunol. 2013 May 1;190(9):4773-85.
Groschwitz KR, Wu D, Osterfeld H, Ahrens R, Hogan SP. Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism. Am J Physiol Gastrointest Liver Physiol. 2013 Mar 1;304(5):G479-89.
Ahrens R, Osterfeld H, Wu D, Chen CY, Arumugam M, Groschwitz K, Strait R, Wang
YH, Finkelman FD, Hogan SP. Intestinal mast cell levels control severity of oral
antigen-induced anaphylaxis in mice. Am J Pathol. 2012 Apr;180(4):1535-46.
Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, Hogan
SP. Colonic eosinophilic inflammation in experimental colitis is mediated by
Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. J Immunol.
2011 May 15;186(10):5993-6003.
Wu D, Ahrens R, Osterfeld H, Noah TK, Groschwitz K, Foster PS, Steinbrecher
KA, Rothenberg ME, Shroyer NF, Matthaei KI, Finkelman FD, Hogan SP. Interleukin-13 (IL-13)/IL-13 receptor alpha1 (IL-13Ralpha1) signaling regulates intestinal epithelial cystic fibrosis transmembrane conductance regulator channel-dependent Cl- secretion. J Biol Chem. 2011 Apr 15;286(15):13357-69.
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. 2011 Feb 3;12:14.
Munitz A, Cole ET, Waddell 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.
Groschwitz K, Ahrens R, Osterfeld H, Gurish MF, Abrink M, Finkelman F, 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
Vascular Endothelium-C-Abl Kinase Underpins the Onset of a Severe Food-induced Anaphylactic Reaction. Principal Investigator. Food Allergy and Research Education. Jul 2015 - Jun 2020.
Leukocyte Immunoglobulin-like Receptor B3 in Innate Colonic Inflammation in Pediatric Ulcerative Colitis. Principal Investigator. Crohn’s and Colitis Foundation of America. Jul 2014 - Jun 2017.
Epithelial Genes in Allergic Inflammation. Project 2 – Collaborating Investigator. National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAIDS). Sep 2006-Aug 2016.
Eosinophil:M2 Macrophage:CCL11 Axis in Experimental Colitis and Pediatric Corticosteroid Resistant Ulcerative Colitis. Principal Investigator. National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK). Apr 2012-Mar 2016.
Enteropathy in Liver-specific pIgA Receptor Knockout Mice. Co-Investigator. Melinda and Bill Gates Foundation. Sep 2013 - Aug 2015.
Leah C. Kottyan, PhD
studies the molecular and immunological mechanisms driving the statistical association of genetic variants with systemic lupus erythematosus and eosinophilic esophagitis. The goal of her research is to refine the statistical analysis of genetic data while using analytical and biological tools to predict and confirm genetic variant-dependent differences that affect gene expression, cell function, and disease risk.
Genetic basis of lupus; genetic basis of eosinophilic esophagitis; immunological mechanisms mediating genetic association with disease
Visit the Kottyan Lab.
For the past decade, many geneticists have approached genetic analysis with the idea that they simply need to increase statistical power by enlarging the sample size (e.g. ~100,000 person height GWAS) and assess enough loci in order to find the “genes” associated with a disease. Unfortunately, clinicians can do relatively little with this type of correlative genetic information. Dr. Kottyan recently lead a genome-wide association analysis of eosinophilic esophagitis in which they went beyond the identification of nine new risk loci and identified the molecular, tissue-specific mechanisms through which genetic variants at the CAPN14 locus increase risk of disease.
During her post-doctoral fellowship, she optimized statistical modeling strategies using genetic data from large multi-ancestral cohorts to identify candidate genetic causal variants through complementary frequentist and Bayesian approaches. In genetic analysis, it is easy and even tempting to make a story out of a genetic variant that seems important. Using two types of statistical analyses on multiple cohorts of different ancestry helps to avoid the misplaced attribution of causality. Instead, Dr. Kottyan’s group develops a short list of variants that are most statistically likely to be causal before they start biological or functional analysis. Once identified, the group predicts and confirms biological phenotypes that are affected by the risk variants.
BA: Chemistry and Cell Biology, Huntingdon College, Montgomery, AL, 2005.
PhD: Immunobiology, University of Cincinnati, Cincinnati, OH, 2010.
Lu X, Zoller EE, Weirauch M, Wu X, Namjou-Khales B, Williams A, Ziegler J, Comeau MR, Marion M, Glenn S, Adler A, Shen N, Nath SK, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown E, Gilkeson G, Alarcon GS, Reveille JD, Anaya JM, James JA, Sivils K, Criswell LA, Vila LM, Alarcon-Riquelme M, Petri M, Scofield RH, Kimberly R, Ramsey-Goldman R, Joo YB, Choi J, Bae SC, Boackle SA, Cunninghame-Graham DS, Vyse T, Guthridge JM, Gaffney PM, Langefeld CD, Kelly J, Greis K, Kaufman K, Harley JB, Kottyan L. Lupus risk-variant increases pSTAT1 binding and decreases ETS1 expression. American journal of human genetics. 2015.
Vaughn SE, Foley C, Lu X, Patel ZH, Zoller EE, Magnusen AF, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath S, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Reveille JD, Anaya J-M, James JA, Moser KL, Criswell LA, Vilá LM, Alarcón-Riquelme ME, Petri M, Scofield RH, Kimberly RP, Ramsey-Goldman R, Binjoo Y, Choi J, Bae S-C, Boackle SA, Vyse TJ, Guthridge JM, Namjou B, Gaffney PM, Langefeld CD, Kaufman KM, Kelly JA, Harley ITW, Harley JB, Kottyan LC. Lupus risk variants in the PXK locus alter B-cell receptor internalization. Frontiers in Genetics. 2015 Jan 8;5:450.
Kottyan LC, Weirauch MT, Rothenberg ME. Making it Big in Allergy. J Allergy Clin Immunol. 2015 Jan;135(1):43-5.
Makashir SB, Kottyan LC, Weirauch MT. Meta-analysis of Differential Gene Co-expression: Application to Lupus. Pacific Symposium on Biocomputing Proceedings. 2015.
Brungs L, Lele A, Kottyan L, Levy B, Moncrieffe H. Genetic Basis of Rheumatic Diseases and the Importance of GWAS in Paediatric Rheumatology. Annals of Pediatric Rheumatology. 2015;3(3):105-115.
Verma SS, de Andrade M, Tromp G, Kuivaniemi H, Pugh E, Namjou-Khales B,
Mukherjee S, Jarvik GP, Kottyan LC, Burt A, Bradford Y, Armstrong GD,
Derr K, Crawford DC, Haines JL, Li R, Crosslin D, Ritchie MD. Imputation
and quality control steps for combining multiple genome-wide datasets.
Frontiers in Genetics. 2014 Dec 11;5:370.
Kottyan LC, Zoller EE, Bene J, Lu X, Kelly JA, Rupert AM, Lessard CJ, Vaughn SE, Marion M, Weirauch MT, Namjou B, Adler A, Rasmussen A, Glenn S, Montgomery CG, Hirschfield GM, Xie G, Coltescu C, Amos C, Li H, Ice JA, Nath SK, Mariette X; Simon Bowman for UK primary Sjögren's syndrome registry, Rischmueller M, Lester S, Brun JG, Gøransson LG, Harboe E, Omdal R, Cunninghame-Graham DS, Vyse T, Miceli-Richard C, Brennan MT, Lessard JA, Wahren-Herlenius M, Kvarnström M, Illei GG, Witte T, Jonsson R, Eriksson P, Nordmark G; Wan-Fai Ng for UK primary Sjögren's syndrome registry, Anaya JM, Rhodus NL, Segal BM, Merrill JT, James JA, Guthridge JM, Scofield RH, Alarcon-Riquelme M, Bae SC, Boackle SA, Criswell LA, Gilkeson G, Kamen DL, Jacob CO, Kimberly R, Brown E, Edberg J, Alarcón GS, Reveille JD, Vilá LM, Petri M, Ramsey-Goldman R, Freedman BI, Niewold T, Stevens AM, Tsao BP, Ying J, Mayes MD, Gorlova OY, Wakeland W, Radstake T, Martin E, Martin J, Siminovitch K, Moser Sivils KL, Gaffney PM, Langefeld CD, Harley JB, Kaufman KM. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Hum Mol Genet. 2014 Jan 15;24(2):582-98.
Namjou B, Ni Y, Harley IT, Chepelev I, Cobb B, Kottyan LC, Gaffney PM, Guthridge JM, Kaufman K, Harley JB. The effect of inversion at 8p23 on BLK association with lupus in Caucasian population. PLoS One. 2014 Dec 29;9(12):e115614.
Alexander ES, Martin LJ, Collins MH, Kottyan LC, Sucharew H, He H, Mukkada VA, Succop PA, Abonia JP, Foote H, Eby MD, Grotjan TM, Greenler AJ, Dellon ES, Demain JG, Furuta GT, Gurian LE, Harley JB, Hopp RJ, Kagalwalla A, Kaul A, Nadeau KC, Noel RJ, Putnam PE, von Tiehl KF, Rothenberg ME. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis. J Allergy Clin Immunol. 2014 Nov;134(5):1084-1092.
Fardo DW, Zhang X, Ding L, He H, Kurowski B, Alexander ES, Baye TM, Pilipenko V, Kottyan L, Nandakumar K, Martin LJ. On Family-based Genome-wide Association Studies with Large Pedigrees: Observations and Recommendations. BMC Proceedings. 2014;8(1):s26-s26.
Michelle B. Lierl, MD Clinical Allergist, Division of Allergy and Immunology
Clinical Allergist, Division of Allergy and Immunology
Adjunct Professor, UC Department of Pediatrics
Treatment and prevention of asthma; allergic rhinitis; allergen immunotherapy; eczema; food allergy; anaphylaxis; suspected immune deficiency
Michelle B. Lierl, MD, is board-certified in pediatrics, pediatric pulmonary medicine and allergy/immunology. Dr. Lierl's primary clinical interests are diagnosis and treatment of asthma, allergic rhinitis, chronic cough, food, latex, insect venom and drug allergies, and eczema.
Dr. Lierl has been treating allergy patients in the Allergy Clinic and Asthma Center, which provides state-of-the-art diagnosis and treatment of asthma and allergies, as well as comprehensive patient education regarding these diseases. She has developed community outreach and patient / family education programs for urban children with asthma and their families.
Dr. Lierl also helps staff the allergy inpatient service, which provides consultation for the management of patients with difficult-to-manage asthma, suspected drug allergies, anaphylaxis, or suspected immune deficiency.
MD: University of Kentucky College of Medicine, Lexington, KY, 1979.
Residency: University of Kentucky Medical Center, Lexington, KY, 1979 to 1982.
Fellowship: Pediatric Pulmonary Medicine, Louisiana State University Medical Center, Shreveport, LA, 1984 - 1986; Allergy / Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 1986 - 1988.
Certification: Pediatrics, 1984; Allergy / Immunology, 1987; Pediatric Pulmonary, 1989, 1996, 2002.
Lierl MB. Management of mild to moderate pediatric asthma. Infect Dis Child. 2011 Dec;supplement: 8-12.
Lierl MB. Allergen immunotherapy: Shots for asthma, wheezing and bee sting. Ped Annals. 2011 Apr;40:192-199.
Spanier AJ, Kahn RS, Hurnung RW, Lierl MB, Lanphear BP. Associations of Fraction of Exhaled Nitric Oxide with Beta Agonist Use in Children with Asthma. Pediatric Allergy, Immunology, and Pulmonology. 2011 Mar;24(1):45-50.
Lanphear BP, Hornung RW, Khoury J, Yolton K, Lierl M, Kalkbrenner A. Effects of HEPA air cleaners on unscheduled asthma visits and asthma symptoms for children exposed to secondhand tobacco smoke. Pediatrics. 2011 Jan;127(1):93-101.
Metz KA, Assa'ad A, Lierl MB, Backeljauw P. Allergic reaction to mecasermin. Ann Allergy Asthma Immunol. 2009;103(1):82-3.
Metz KA, Johnson T, Khurana Hershey GK, Lierl MB, Seidu L, Burns K, Assa’ad A. Successful administration of cytarabine in a 16 month old girl with acute myelogenous leukemia and cytarabine syndrome. Ann Allergy, Asthma Immunol. 2009;102:173-4.
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.
Andrew W. Lindsley, MD, PhD
and his lab focuses on two major research questions with significant clinical relevance; the role of sphingolipid signaling in the pathogenesis of pediatric-onset asthma and the mechanisms of humoral immune deficiency. Current B cell projects focus on the B cell defects associated with Kabuki syndrome and abnormal non-canonical NFkB signaling.
Instructor, UC Department of Pediatrics
PhD: Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 2005.
MD: Indiana University School of Medicine, Indianapolis, IN, 2007.
Residency: Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2007-10.
Fellowship: Allergy & Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2010-13.
Certifications: Pediatrics 2013, Allergy & Immunology 2014.
Lindsley AW, Saal HM, Burrow TA, Hopkin RJ, Shchelochkov O, Khandelwal P, Xie C, Bleesing J, Filipovich L, Risma K, Assa’ad AH, Roehrs PA, Bernstein JA. Defects of B Cell Terminal Differentiation in Patients with Type-1 Kabuki Syndrome. J Allergy Clin Immunol. 2015.
Lindsley AW, Qian Y, Valencia CA, Shah K, Zhang K, Assa'ad A. Combined Immune Deficiency in a Patient with a Novel NFKB2 Mutation. J Clin Immunol. 2014 Nov;34(8):910-5.
Lyons JJ, Sun G1, Stone KD, Nelson C1, Wisch L, O'Brien M, Jones N, Lindsley A, Komarow HD, Bai Y, Scott LM, Cantave D, Maric I, Abonia J, Rothenberg ME, Schwartz LB, Milner JD, Wilson TM. Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities. J Allergy Clin Immunol. 2014 May;133(5):1471-4.
Baye T, Kovacic M, Biagini-Myers J, Martin L, Lindsey M, Patterson T, He H, Ericksen M, Gupta J, Tsoras A, Lindsley A, Rothenberg M, Wills-Karp M, Eissa N, Borish L, Hershey G. Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children. PLoS One. 2011 Feb 28;6(2):e16522.
Snider P, Hinton RB, Moreno-Rodriguez RA, Wang J, Rogers R, Lindsley A, Li F, Ingram DA, Menick D, Field L, Firulli AB, Molkentin JD, Markwald R, Conway SJ. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ Res. 2008 Apr 11;102(7):752-60.
Lindsley A, Snider P, Zhou H, Rogers R, Wang J, Olaopa M, Kruzynska-Frejtag A, Koushik SV, Lilly B, Burch JB, Firulli AB, Conway SJ. Identification and characterization of a novel Schwann and outflow tract endocardial cushion lineage-restricted periostin enhancer. Dev Biol. 2007 Jul 15;307(2):340-55.
Lindsley A, Li W, Wang J, Maeda N, Rogers R, Conway SJ. Comparison of the four mouse fasciclin-containing genes expression patterns during valvuloseptal morphogenesis. Gene Expr Patterns. 2005 Jun;5(5):593-600.
Rios H, Koushik S, Wang J, Lindsley A, Wang H, Rogers R, Chen Z, Maeda M, Kruzynska-Frejtag A, Markwald R, Feng J, Conway S. Periostin null mice exhibit dwarfism, cardiac valve anomalies, incisor enamel defects, & an early onset periodontal disease-like phenotype. Mol Cell Biol. 2005 Dec;25(24):11131-44.
Santa Ono, PhD President, University of Cincinnati
Dr. Ono's principal research interests focus on transcriptional regulation in the human immune system, mechanisms of mast-cell dependent inflammation on the ocular surface, and the immune component of age-related macular degeneration.
President, University of Cincinnati
Santa J. Ono, PhD, is a professor of pediatrics at Cincinnati Children's Hospital Medical Center within the University of Cincinnati College of Medicine.
Kimberly A. Risma, MD, PhD Director, Allergy and Immunology Fellowship Program
Director, Allergy and Immunology Fellowship Program
Immune deficiency; immune dysregulation
Kimberly Risma, MD, PhD, is an assistant professor in the Division of Allergy and Immunology at Cincinnati Children’s within the University of Cincinnati College of Medicine.
Dr. Risma graduated magna cum laude with a Bachelor of Arts in chemistry from Duke University in 1990 and was elected into The Phi Beta Kappa Society. She then matriculated at Case Western Reserve University (CWRU) School of Medicine in the Medical Scientist Training Program (MSTP). In 1996, she completed a PhD in pharmacology. She was selected by the leadership of the CWRU MSTP as the recipient of the 1997 Martin Wahl Memorial Fund Award, given annually to recognize the graduating MD, PhD student who has demonstrated the highest level of independence in research and excellence in research and clinical skills. She was also elected to Alpha Omega Alpha Society in 1997.
In 1997, she enrolled in a pediatrics residency at Cincinnati Children’s Hospital Medical Center/University of Cincinnati. During the residency program, Dr. Risma was awarded the pediatric resident teaching award by the medical students. She also engaged in translational research studies related to the genetics of asthma under the mentorship of Dr. Gurjit Hershey, resulting in a first author publication as a pediatric resident.
In 2000, Dr. Risma was accepted to the Allergy and Immunology Fellowship Program at Cincinnati Children’s. In addition to her clinical training, she pursued an innovative research project under the mentorship of Dr. Janos Sumegi and Dr. Alexandra Filipovich. She proposed a mechanism to study the structural and functional impact of perforin missense mutations identified in patients with hemophagocytic lymphohistiocytosis. In 2004 she was awarded the Nezelof Prize for best scientific presentation at the international meeting of the Histiocyte Society. The culmination of her fellowship research project was published in the Journal of Clinical Investigation, 2006.
Upon completion of her fellowship in 2005, Dr. Risma was appointed as an assistant professor in the Division of Allergy and Immunology at Cincinnati Children’s Hospital Medical Center within the UC Department of Pediatrics. In 2006 Dr. Risma received a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. Dr. Risma is the director of the Allergy and Immunology Fellowship Program at Cincinnati Children's, having served in this leadership position since August of 2012.
Dr. Risma's research program focuses on understanding the molecular mechanisms of immunodeficiency and immune dysregulation in children, especially as it relates to disorders of lymphocyte cytotoxicity. In addition to her research, she sees patients from all around the country in consultation for primary immune deficiency, immune dysregulation, and allergic disorders.
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.
Vrazo AC, Hontz AE, Figueira SK, Butler BL, Ferrell JM, Binkowski BF, Li J, Risma KA. Live cell evaluation of granzyme delivery and death receptor signaling in tumor cells targeted by human natural killer cells. Blood. 2015 Jun 29.
Carmo M, Risma KA, Arumugam P, Tiwari S, Hontz AE, Montiel-Equihua CA, Alonso-Ferrero ME, Blundell MP, Schambach A, Baum C, Malik P, Thrasher AJ, Jordan MB, Gaspar HB. Perforin gene transfer into hematopoietic stem cells improvesimmune dysregulation in murine models of perforin deficiency. Mol Ther. 2015 Apr;23(4):737-45.
Li J, Figueira SK, Vrazo AC, Binkowski BF, Butler BL, Tabata Y, Filipovich A, Jordan MB, Risma KA. Real-Time Detection of CTL Function Reveals Distinct Patterns of Caspase Activation Mediated by Fas versus Granzyme B. J Immunol. 2014 Jul 15;193(2):519-28.
Mellor-Heineke S, Villanueva J, Jordan MB, Marsh R, Zhang K, Bleesing JJ, Filipovich AH, Risma KA. Elevated Granzyme B in Cytotoxic Lymphocytes is a Signature of Immune Activation in Hemophagocytic Lymphohistiocytosis. Front Immunol. 2013 Mar 22; 4:72.
Risma K, Jordan MB. Hemophagocytic lymphohistiocytosis: updates and evolving concepts. Curr Opin Pediatr. 2012 Feb;24(1):9-15.
Zhang K, Jordan MB, Marsh RA, Johnson JA, Kissell D, Meller J, Villanueva J, Risma KA, Wei Q, Klein PS, Filipovich AH. Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH. Blood. 2011 Nov 24;118(22):5794-8.
Lykens JE, Terrell CE, Zoller EE, Risma K, Jordan MB. Perforin is a critical physiologic regulator of T-cell activation. Blood. 2011 Jul 21;118(3):618-26.
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.
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.
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.
Yui-Hsi Wang, PhD
investigates the mechanisms that govern the plasticity of tissue resident TH2 memory / effector cells in the airway and gut. Particularly interested in understanding how inflammatory mediators, such as IL-1b, IL-33 and IL-25, regulate the development of IL-17-producing TH2 or IL-9-producing TH2 cells during airway or gastrointestinal allergic inflammation, respectively.
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.
Ting Wen, PhD Researcher, Cincinnati Center for Eosinophilic Disorders
investigates the molecular mechanisms of eosinophilic esophagitis (EoE). His lab's studies focus on identifying novel disease-causing genes and related pathogenic pathways. His research utilizes genome-wide analysis and cutting-edge techniques to provide molecular insight into the pathogenesis of EoE and allergy. Investigating basic eosinophil biology with human samples and mouse models is also an ongoing research interest.
Researcher, Cincinnati Center for Eosinophilic Disorders
Ting Wen, PhD, has characterized the unique, tissue-specific transcriptome of purified murine eosinophils under homeostasis and allergic conditions and demonstrated the expression and function of a couple of unexpected molecules, CD22 and CAR4, on gastrointestinal and lung eosinophils, respectively (Wen et al., 2012 and 2014, Journal of Immunology).
Dr. Wen also developed a murine eosinophil transfer model system that has proven to be useful in assessing the function of a gene of interest that is expressed on eosinophils or target tissue (Wen et al., 2013, PNAS).
Dr. Wen is a co-inventor of the EoE Diagnostic Panel (EDP), created in part due to his expertise in molecular biopsy and bioinformatics. The Cincinnati Children's-owned patent is now licensed to the diagnostic company Diagnovus, LLC, as Engauge GI-EoE test and is in use in clinical practice (Wen et al., 2013, Gastroenterology).
In the past three years, Dr. Wen won the following awards for his eosinophil-related studies:
Dr. Wen has also been an invited speaker on several national and international meetings related to eosinophilic disorders and co-authored to two book chapters.
PhD: Cell Biology and Neuroscience, University of Medicine and Dentistry of New Jersey / Rutgers University, Piscataway, NJ.
Postdoctoral Fellowship: Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Wen T, Dellon ES, Moawad FJ, Furuta GT, Aceves SS, Rothenberg ME. Transcriptome analysis of proton pump inhibitor-responsive esophageal eosinophilia reveals proton pump inhibitor-reversible allergic inflammation.
J Allergy Clin Immunol. 2014;S0091-6749(14)01271-8.
Wen T, Mingler MK, Wahl B, Pabst O, Khorki EM, Zimmermann N, Rothenberg ME. Carbonic anhydrase IV (CAR4) is an activation marker of murine lung eosinophils. Journal of Immunology. 2014;192(12):5481-9.
Butz BK*, Wen T*, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014;147(2):324-33.e5. * Co-1st-author
Rothenberg ME, Wen T, Greenberg A, Hirano I, Nadeau K, Alpan O, Wright A, Espié P, Arm J, Strieiter R, Sabo R, Gunawardena KA. A double-blinded, randomized, placebo-controlled trial of intravenous anti-IL-13 AQX576 in the treatment of eosinophilic esophagitis. J Allergy Clin Immunol. 2014 Sep 13;pii:S0091-6749(14)01053-7.
Wen T, Besse JA, Mingler MK, Fulkerson PC, Rothenberg ME. Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil trafficking in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(15):6067-6072.
Abonia JP, Wen T, Stucke EM, Grotjan T, Griffith MS, Kemme KA, Collins MH, Putnam PE, Franciosi JP, von Tiehl KF, Tinkle BT, Marsolo KA, Martin LJ, Ware SM, Rothenberg ME. High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders. Journal of Allergy and Clinical Immunology. 2013;132(2):378-386.
Wen T, Stucke EM, Grotjan TM, Kemme KA, Abonia JP, Putnam PE, Franciosi JP, Garza JM, Kaul A, King EC, Collins MH, Kushner JP, Rothenberg ME. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology. 2013;145(6):1289-1299.
Wen T, Mingler MK, Blanchard C, Wahl B, Pabst O, Rothenberg ME. The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia. Journal of Immunology. 2012;188(3):1075-1082.
Wen T, Peng B, Pintar JE. The MOR-1 opioid receptor regulates glucose homeostasis by modulating insulin secretion. Molecular Endocrinology. 2009;23(5):671-678.
Wen T, Ansonoff MA, Pintar JE. The tail pigmentation pattern of C57BL/6J mice affects nociception/pain quantification in the tail flick test. European Journal of Pain. 2009;13(6):564-567.
Nives Zimmermann, MD Director of MS Track, Immunology Graduate Program
Director of MS Track, Immunology Graduate Program
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.
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