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Marc E. Rothenberg, MD, PhD Director, Division of Allergy and Immunology
Director, Division of Allergy and Immunology
Director, Cincinnati Center for Eosinophilic Disorders
Professor, UC Department of Pediatrics
Eosinophilia; eosinophilic disorders; asthma; allergy; food allergy
Visit the Rothenberg Lab.
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; In press.
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.
Immunobiology of Peanut Allergy and It’s Treatment. Co-Investigator. National Institutes of Health. Jul 2010–Jun 2015. U19 AI066738.
Regulation of Gastrointestinal Eosinophils. Principal Investigator. National Institutes of Health. Dec 2009–Nov 2014. R37 AI045898.
Cincinnati Center for Clinical and Translational Science and Training. Co-Program Director. National Institutes of Health. Apr 2009–Mar 2015. KL2 TR000078.
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.
Margaret H. Collins, MD
Professor, UC Department of Pathology & Laboratory Medicine
Pediatric gastrointestinal pathology; eosinophilic gastrointestinal diseases; biopsy analyses; primary study endpoints; novel therapies to treat eosinophilic esophagitis in children; disorders of bowel immunity; bowel motility disorders
BS: Fordham University, NY, 1972.
MD: Georgetown University, Washington, D.C., 1977.
Residency: Pathology, New York Hospital, NY, 1977-80; Pathology, Columbia-Presbyterian Medical Center, NY, 1980-83.
Fellowship: Research, New York Lung Association, Columbia-Presbyterian Medical Center, N.Y., 1983-85; Research, American Lung Association, Columbia-Presbyterian Medical Center, NY, 1985-87.
Certification: Pathology, 1981; Pediatric Pathology, 1991.
Nikolaidis NM, Kulkarni RM, Gray JK, Collins MH, Waltz SE. Ron receptor deficient alveolar myeloid cells exacerbate LPS-induced acute lung injury in the murine lung. Innate Immun. 2010 Nov 18.
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.
Caldwell JM, Blanchard C, Collins MH, Putnam PE, Kaul A, Aceves SS, Bouska CA, Rothenberg ME. Glucocorticoid-regulated genes in eosinophilic esophagitis: a role for FKBP51. J Allergy Clin Immunol. 2010 Apr;125(4):879-888.e8.
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.
Blanchard C, Stucke EM, Burwinkel K, Caldwell JM, Collins MH, Ahrens A, Buckmeier BK, Jameson SC, Greenberg A, Kaul A, Franciosi JP, Kushner JP, Martin LJ, Putnam PE, Abonia JP, Wells SI, Rothenberg ME. Coordinate interaction between IL-13 and epithelial differentiation cluster genes in eosinophilic esophagitis. J Immunol. 2010 Apr 1;184(7):4033-41.
Miller SJ, Lan ZD, Hardiman A, Wu J, Kordich JJ, Patmore DM, Hegde RS, Cripe TP, Cancelas JA, Collins MH, Ratner N. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 2010 Jan 21;29(3):368-79.
Vicario M, Blanchard C, Stringer KF, Collins MH, Mingler MK, Ahrens A, Putnam PE, Abonia JP, Santos J, Rothenberg ME. Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut. 2010 Jan;59(1):12-20.
Prosperi JR, Becher KR, Willson TA, Collins MH, Witte DP, Goss KH. The APC tumor suppressor is required for epithelial integrity in the mouse mammary gland. J Cell Physiol. 2009 Aug;220(2):319-31.
Patricia C. Fulkerson, MD, PhD
Assistant Professor, UC Department of Pediatrics
Eosinophilic disorders; immunodeficiency; immune dysregulation
Visit the Fulkerson Lab web site.
Patricia C. Fulkerson, MD, PhD, is an assistant professor of pediatrics at Cincinnati Children’s Hospital Medical Center and 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.
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.
Ahrens R, Osterfeld H, Wu D, Arumugam M, Groschwitz K, Strait RA, Finkelman FD, Hogan SP. Intestinal mast cell levels influence severity of oral antigen-induced anaphylaxis. Am J Pathol. 2012 Apr;180(4):1535-46.
Beichler A, Ahrens R, Steinbrecher K, Rothenberg ME, Munitz A, Denson L, Hogan SP. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C+ CCR2+ inflammatory monocyte-derived CCL11. J Immunol. 2011 May 15;186(10):5993-6003.
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.
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. Journal of Biological Chemistry. 2011;286(15), 13357-13369.
Osterfeld H, Ahrens R, Strait R, Rothenberg ME, Finkelman FD, Renauld JC, Hogan SP. Divergent roles for the IL9/IL9R-pathway in systemic antigen- and oral antigen-induced anaphylaxis. J Allergy Clin Immunol. 2010;125: 469-476.
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;139(2), 530-541.
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. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(52), 22381-22386.
Ahrens R, Waddell A, Seidu L, Blanchard, C, Carey R, Forbes E, Lampinen M, Willson 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. The Journal of Immunology. 2008;181(10), 7390-7399.
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. The Journal of Experimental Medicine. 2008;205(4), 897-913.
MiR-375 regulation of CFTR expression and Cl- secretory function. Principal Investigator. Cystic Fibrosis Foundation. Jul 2012-Jun 2014.
Eosinophil:M2 Macrophage:CCL11 Axis in Experimental Colitis and Pediatric Corticosteroid Resistant UC. Principal Investigator. National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK). Apr 2012-Mar 2016.
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.
Leah C. Kottyan, PhD
Genetic basis of lupus; genetic basis of eosinophilic esophagitis; immunological mechanisms mediating genetic association with disease
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.
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. Human Molecular Genetics. 2014 Sep 8. Epub ahead of print.
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 That Explain High Heritability of Eosinophilic Esophagitis. Journal of Clinical Allergy and Immunology. 2014 Sep 1. Epub ahead of print.
Lu-Fritts PY, Kottyan LC, James JA, Xie C, Buckholz JM, Pinney SM, Harley JB. Systemic Lupus Erythematosus is Associated with Uranium Exposure in a Community Living Near a Uranium Processing Plant: A Nested Case-Control Study. Arthritis and Rheumatology. 2014 Aug 7. Epub ahead of print.
Kottyan LC, Davis BP, Sherrill JD, Liu K, Rochman M, Kaufman K, Weirauch MT, Vaughn S, Lazaro S, Rupert AM, Kohram M, Stucke EM, Kemme KA, Magnusen A, He H, Dexheimer P, Chehade M, Wood RA, Pesek RD, Vickery BP, Fleischer DM, Lindbad R, Sampson HA, Mukkada VA, Putnam PE, Abonia JP, Martin LJ, Harley JB, Rothenberg ME. Identification of genome-wide susceptibility loci for eosinophilic esophagitis elucidates tissue-specificity of this allergic disease. Nature Genetics. 2014;46(8):895-900.
Martin LJ, Pilipenko V, Kaufman KM, Cripe L, Kottyan LC, Keddache M, Dexheimer P, Weirauch MT, Benson DW. Whole Exome Sequencing for Familial Bicuspid Aortic Valve Identifies Putative Variants. Circulation: Cardiovascular Genetics. 2014 Aug 1. Epub ahead of print.
Kottyan LC, Patel ZH, Lazaro S, Williams MS, Ledbetter DH, Tromp H, Rupert A, Kohram M, Wagner M, Husami A, Qian Y, Valencia CA, Zhang K, Hostetter MK, Harley JB, Kaufman KM. The struggle to find reliable results in exome sequencing data: filtering out Mendelian errors. Front Genet. 2014;12;5:16.
Kim-Howard X, Sun C, Molineros JE, Maiti AK, Chandru H, Adler A, Wiley GB, Kaufman KM, Kottyan L, Guthridge JM, Rasmussen A, Kelly J, Sanchez E, Raj P, Li QZ, Bang SY, Lee HS, Kim TH, Kang YM, Suh CH, Chung WT, Park YB, Choe JY, Shim SC, Lee SS, Han BG, Olsen NJ, Karp DR, Moser K, Pons-Estel BA, Wakeland EK, James JA, Harley JB, Bae SC, Gaffney PM, Alarcon-Riquelme M, on behalf of G, Looger LL, Nath SK. Allelic heterogeneity in NCF2 associated with systemic lupus erythematosus (SLE) susceptibility across four ethnic populations. Human molecular genetics. 2013.
Vaughn SE, Kottyan LC, Munroe ME, Harley JB. Genetic susceptibility to lupus: the biological basis of genetic risk found in B cell signaling pathways. Journal of leukocyte biology. 2012;92(3):577-91.
Uccellini L, De Giorgi V, Zhao Y, Tumaini B, Erdenebileg N, Dudley ME, Tomei S, Bedognetti D, Ascierto ML, Liu Q, Simon R, Kottyan L, Kaufman KM, Harley JB, Wang E, Rosenberg SA, Marincola FM. IRF5 gene polymorphisms in melanoma. Journal of translational medicine. 2012;10:170.
Kottyan LC, Woo JG, Keddache M, Banach W, Crimmins NA, Dolan LM, Martin LJ. Novel variations in the adiponectin gene (ADIPOQ) may affect distribution of oligomeric complexes. SpringerPlus. 2012;1(1):66.
Immunobiology of Peanut Allergy and its Treatment. Investigator. National Institutes of Health. July 2010-June 2015.
Genetic Linkage in Lupus. Investigator. National Institutes of Health. July 1987-February 2015.
Vincent A. Mukkada, MD
Eosinophilic gastrointestinal disorders; pediatric feeding problems; general pediatric gastroenterology; celiac disease
BA: University of Pennsylvania, Philadelphia, PA, 1998.
MD: University of Cincinnati, Cincinnati, OH, 2002.
Residency: Pediatrics, Brown University / Hasbro Children’s Hospital, Providence, RI, 2002-2005.
Fellowship: Pediatric Gastroenterology, University of Colorado / Children’s Hospital of Colorado, Denver, CO, 2005-2008.
Research Scholar: University of Colorado / Children’s Hospital of Colorado, Denver, CO, 2008-2009.
Certifications: General Pediatrics, 2005; Pediatric Gastroenterology, 2009.
Ngo PD, Macleod RJ, Mukkada V, Turki R, Furuta GT. Epithelial calcium-sensing receptor activation by eosinophil granule protein analog stimulates collagen matrix contraction. Pediatr Res. 2012 Dec 26.
Furuta GT, Kagalwalla AF, Lee JJ, Alumkal P, Maybruck BT, Fillon S, Masterson JC, Ochkur S, Protheroe C, Moore W, Pan Z, Amsden K, Robinson Z, Capocelli K, Mukkada V, Atkins D, Fleischer D, Hosford L, Kwatia MA, Schroeder S, Kelly C, Lovell M, Melin-Aldana H, Ackerman SJ. The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis. Gut. 2012 Aug 15.
Kagalwalla AF, Akhtar N, Woodruff SA, Rea BA, Masterson JC, Mukkada V, Parashette KR, Du J, Fillon S, Protheroe CA, Lee JJ, Amsden K, Melin-Aldana H, Capocelli KE, Furuta GT, Ackerman SJ. Eosinophilic esophagitis: epithelial mesenchymal transition contributes to esophageal remodeling and reverses with treatment. J Allergy Clin Immunol. 2012 May;129(5):1387-1396.e7.
Lu S, Mukkada VA, Mangray S, Cleveland K, Shillingford N, Schorl C, Brodsky AS, Resnick MB. MicroRNA profiling in mucosal biopsies of eosinophilic esophagitis patients pre and post treatment with steroids and relationship with mRNA targets. PLoS One. 2012;7(7):e40676.
Mukkada VA, Haas A, Maune NC, Capocelli KE, Henry M, Gilman N, Petersburg S, Moore W, Lovell MA, Fleischer DM, Furuta GT, Atkins D. Feeding dysfunction in children with eosinophilic gastrointestinal diseases. Pediatrics. 2010 Sep;126(3):e672-7.
Protheroe C, Woodruff SA, de Petris G, Mukkada V, Ochkur SI, Janarthanan S, Lewis JC, Pasha S, Lunsford T, Harris L, Sharma VK, McGarry MP, Lee NA, Furuta GT, Lee JJ. A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2009 Jul;7(7):749-755.e11.
Mukkada V, Atkins D, Furuta GT. The perplexing finding of esophageal eosinophilia. Am J Gastroenterol. 2008 Sep;103(9):2403.
Mukkada V, Atkins D, Furuta GT. Uncertain association of Barrett's esophagus with eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2008 Jul;6(7):832.
Mukkada VA, Furuta GT. Idiopathic eosinophilic disorders of the gastrointestinal tract in children. Best Pract Res Clin Gastroenterol. 2008;22(3):497-509.
Wong BL, Mukkada VA, Markham LW, Cripe LH. Depressed left ventricular contractile reserve diagnosed by dobutamine stress echocardiography in a patient with Duchenne muscular dystrophy. J Child Neurol. 2005 Mar;20(3):246-8.
Philip E. Putnam, MD Director, Endoscopy Services
Director, Endoscopy Services
Eosinophilic enteritis; abdominal pain; gastroesophageal reflux; complex nutrition related to the GI tract; GI bleeding; inflammatory bowel disease; diarrhea and failure to thrive
MD: University of Michigan Medical School, Ann Arbor, MI, 1984.
Residency: University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA, 1984-1987.
Fellowship: University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA, 1988-1991.
Certification: Pediatrics, 1988; Pediatric Gastroenterology, 1995.
Kimberly A. Risma, MD, PhD Director, Allergy and Immunology Fellowship Program
Director, Allergy and Immunology Fellowship Program
Immune deficiency; immune dysregulation
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
Visit the Risma Lab website.
Kimberly Risma, MD, PhD, is an assistant professor in the Division of Allergy and Immunology at Cincinnati Children’s and 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. 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.
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.
Uygungil B, Assa'Ad A, Khurana Hershey GK, Risma K. Immunodeficiency: a problem with the faucet or the drain? Ann Allergy Asthma Immunol. 2011 Dec;107(6):547-9.
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.
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.
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.
Joseph D. Sherrill, PhD
Instructor, UC Department of Pediatrics
PhD: University of Cincinnati, Cincinnati, OH, 2008.
Research Fellowship: Division of Allergy and Immunology, Cincinnati Children’s, Cincinnati, OH, 2008-2012.
Sherrill JD, Rothenberg ME. Genetic dissection of eosinophilic esophagitis provides insight into disease pathogenesis and treatment strategies. Journal of Allergy and Clinical Immunology. 2011;128(1):23-32.
Sherrill JD, Gao P, Stucke EM, Blanchard C, Collins MH, Putnam PE, Franciosi JP, Kushner JP, Abonia JP, Assa’ad AH, Butsch Kovacic M, Biagini Meyers JM, Bochner BS, He H, Khurana Hershey G, Martin LJ, Rothenberg ME. Variants of thymic stromal lymphopoietin and its receptor associate with eosinophilic esophagitis. Journal of Allergy and Clinical Immunology. 2010;126(1):160-5.
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. Nature Genetics. 2010;42(4):289-91. *co-first author
Sherrill JD, Stropes MP, Schneider OD, Koch DE, Bittencourt FM, Miller JLC, Miller WE. Activation of intracellular signaling pathways by the murine cytomegalovirus G protein-coupled receptor M33 occurs via PLC-beta/PKC-dependent and -independent mechanisms. Journal of Virology. 2009;83(16):8141-52.
Sherrill JD, Miller, WE. Desensitization of Herpes-virus-encoded G protein-coupled receptors. Life Sciences. 2007;82(3-4):125-34.
Sherrill JD, Miller WE. G protein-coupled receptor (GPCR) kinase 2 regulates agonist-independent Gq/11 signaling from the mouse cytomegalovirus GPCR M33. Journal of Biological Chemistry. 2006;281(52):39796-805.
Nicole E. Zahka, PhD Clinical Psychologist, Behavioral Medicine and Clinical Psychology
Clinical Psychologist, Behavioral Medicine and Clinical Psychology
Adjustment to chronic illness; adolescence; anxiety and related disorders; individual and family therapy; psychological assessment
Alison Cassin, MS, RD, LD Registered Dietitian, Cincinnati Center for Eosinophilic Disorders
Leandre M. Gerwin, MA, CCC-SLP Speech-Language Pathologist II, Division of Speech-Language Pathology
Erin A. Holbrook, MSW, LISW Social Worker II, Division of Social Services
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