New Leadership for Division Research
Simon P. Hogan, PhD was recently appointed as the Director of Research of the Division of Allergy/Immunology. He joins the Division Director, Marc E. Rothenberg, MD, PhD, and Amal H. Assa'ad, MD, Associate Division Director and Division Clinical Director, in leading the division to new heights to improve the health of children with allergic and immune conditions through innovative research, outstanding clinical care and education of the current and next generation of leaders in healthcare and research.
New Leadership for Allergy/Immunology Fellowship Program
Kimberly A. Risma, MD, PhD has assumed the role of Fellowship Director of the Allergy/Immunology Fellowship Program. Risma is dedicated to teaching our future allergists in this combined pediatric and adult fellowship program (via partnership with the University of Cincinnati). This program is an integral part of our division's mission to improve the health of children with allergic and immune conditions through the education of the current and next generation of leaders in healthcare and research.
New Leadership for Advancing Mechanistic Allergy and Asthma Research
Nives Zimmermann, MD has assumed the position of Vice Chair of the Mechanism of Allergy and Asthma interest section of the American Academy of Allergy, Asthma and Immunology (AAAAI). In this position, she will provide leadership to the constituents with an interest in mechanistic research and a central role in the planning of the AAAAI annual conference.
Division Researcher Appointed President at the University of Cincinnati
University of Cincinnati President Santa J. Ono, PhD, Professor within the Division of Allergy and Immunology, was appointed as the 28th President at the University of Cincinnati. Prior to his presidency, Ono served for two years as the Senior Vice President for Academic Affairs and Provost. In addition to his institutional leadership and service, Ono leads an active research program. His 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.
Director, Registry for Eosinophilic Disorders (REGID)
J. Pablo Abonia, MD assesses the clinical biology and regulation of mast cells and their role in diseases, such as eosinophilic esophagitis, eosinophilic gastrointestinal disorders and primary mast cell disease. He conducts translational research and clinical trials in conjunction with developing patient databanks and bioinformatic approaches to further understand allergic disease. A member of the Cincinnati Center for Eosinophilic Disorders, Abonia was recently appointed the Director of the Registry for Eosinophilic Gastrointestinal Disorders (REGID), a national not-for-profit collaboration of medical centers, professionals, families and individuals dedicated to improving the knowledge, research and outcomes for people living with eosinophilic gastrointestinal disorders.
Division Director Discovers miRNAs Controlling Eosinophilopoeisis
Marc E. Rothenberg, MD, PhD has identified roles for two miRNAs, miR-21 and miR-223, in controlling eosinophilopoiesis, the generation of eosinophils. miR-21 has previously been shown to regulate T-cell polarization and activation in preclinical models and to be dysregulated in an miRNA signature that correlates with disease activity for eosinophilic esophagitis (EoE), a severe food allergy. miR-21 is one of the most upregulated miRNAs in multiple allergic diseases associated with eosinophilia and has long been shown to positively correlate with eosinophil levels. Using a murine interleukin-5 (IL-5)-driven eosinophil differentiation model and gene expression microarray analysis, Rothenberg showed that targeted ablation of miR-21 in decreased eosinophil progenitor cell growth. In a related study, Rothenberg demonstrated a similarly important role for miR-223 in regulating eosinophil progenitor growth and differentiation, with miR-223 deficiency increasing eosinophil progenitor proliferation. Identification of the role miRNAs in eosinophilopoiesis and the specific miRNAs involved are critical advancements for the development of biomarkers, therapies and eventual cures for allergic disease.
Division Research Director Furthers Understanding of Intestinal Epithelial Barrier Homeostasis
Simon P. Hogan, PhD identified a role for the mast cell–derived serine protease chymase in the regulation of intestinal epithelial barrier homeostasis. As published in the American Journal of Physiology - Gastrointestinal and Liver Physiology, Hogan employed in vitro model systems to delineate the molecular pathways involved in chymase-mediated intestinal epithelial barrier dysfunction and demonstrated that chymase-mediated modulation of intestinal epithelial barrier was characterized by chymase-induced protease-activated receptor (PAR)-2 activation and matrix metalloproteinase (MMP)-2 expression and activation. Importantly, pharmacological and small interfering RNA-mediated antagonism of PAR-2 and MMP-2 significantly attenuated chymase-stimulated barrier dysfunction. Collectively, these results suggest that mast cell/chymase-mediated intestinal epithelial barrier function is mediated by PAR-2/MMP-2-dependent pathways.'
Division Researcher Investigates Epigenomics of Immunology
Artem Barski, PhD is interested in the epigenetic and transcriptional regulation of gene expression and contributed to the development of ChIP-Seq, a revolutionary method that combines chromatin immunoprecipitation (ChIP) with the next-generation sequencing (Seq). Epigenomics is a cutting-edge field that elucidates the importance of how reversible modifications of DNA or histones can alter expression of genes or genetic variants during homeostasis or disease. Using ChIP-Seq and other sequencing-based genome-wide methods, Barski investigates the role of chromatin modifications in gene regulation, including his recent work with chromatin regulation of genes transcribed by RNA polymerase III and the discovery of gene poising in T cells. He is currently researching the epigenetic basis of T-cell activation, memory and tolerance.
Division Researcher Discovers Mechanism of Eosinophil Cell Death
Nives Zimmermann, MD was the senior author for “Mechanism of Siglec-8-mediated cell death in IL-5-activated eosinophils: role for reactive oxygen species-enhanced MEK/ERK activation”, which was recently published in the Journal of Allergy and Clinical Immunology. This study, led by Gen Kano, MD, PhD and performed in collaboration with Dr. Bruce Bochner from Johns Hopkins University, discovered a novel mechanism of cell death in activated eosinophils. This finding is significant because eosinophil cell death, accompanied by release of toxic granule content in tissue, contributes to the pathophysiology of multiple diseases, including allergic diseases. The ability to inhibit this novel pathway of regulated necrosis could lead to improved therapies for these diseases. As a result of this study and its potential impact, Zimmermann was awarded a grant from the American Heart Association to study the molecular mechanisms of eosinophil cell death, in collaboration with Dr. Margaret Collins, Department of Pathology.
Division Clinician Researcher Pursues Development of High-Throughput Screening Assay for Hemophagocytic Lymphohistiocytosis Therapeutics
Kimberly A. Risma, MD, PhD developed and executed the first known microplate assay screen for small-molecule enhancers of natural killer (NK) cell and cytotoxic T lymphocyte function. This study provided critical preliminary data that will permit adaptation and execution of a much larger high-throughput screen this year, in collaboration with the NIH Molecular Libraries Program. Using patient-derived primary NK cells, Risma will screen a library of FDA-approved compounds for cytotoxic enhancers of NK cell function in an attempt to repurpose drugs already in clinical use. This research effort has great potential to ultimately change the outcome for children with inherited defects in cytotoxic function associated with the potentially fatal disorder, hemophagocytic lymphohistiocytosis (HLH). More broadly, the results of this research may eventually provide alternative treatments in cancer and/or chronic viral infections.
Division Clinician Researcher Dedicated to Fungal Spore Research
Michelle B. Lierl, MD is conducting a study investigating the role of outdoor fungal and myxomycete spores as aeroallergens; this study involves allergy skin testing with myxomycete and basidiomycete spore extracts to identify whether they are previously unrecognized aeroallergens. As no extracts of these spores were commercially available, Lierl collects the spores herself and makes the extracts for the allergy skin testing. Having discovered the lack of photographs available of these microscopic spores, she also maintains a website to share photographs of spores of basidiomycetes, ascomycetes, and myxomycetes as a reference source for others for fungal species identification.
Division Clinical Director Supports Cincinnati Children's National and Global Mission
Amal H. Assa'ad, MD has exemplified the national and global mission of Cincinnati Children’s through her far-reaching dedication and valued efforts to improve child health. She has represented Cincinnati Children’s as an invited speaker at plenary sessions and international symposia at four international meetings, in Israel, Italy, Mexico, and India. In addition, she serves as an elected member of the American Academy of Allergy, Asthma and Immunology (AAAAI) Board of Directors; chaired and organized the 2012 American College of Allergy, Asthma & Immunology (ACAAI) Food Allergy Symposium; and co-authored a well-received publication in the Journal of Allergy and Clinical Immunology about preventing allergic disease through nutritional interventions. Her efforts abroad are coupled with her local leadership in clinical care and clinical research trials, with her work in food allergy being recognized with the prestigious Luisa Businco Lectureship and Award by the ACAAI.