Faculty Research
Marc E. Rothenberg, MD, PhD
The Rothenberg laboratory is focused on elucidating the mechanisms of allergic responses especially in mucosal tissues such as the lung and the gastrointestinal tract. The goal of the research is to identify novel pharmaceutical targets for the treatment of patients with eosinophil associated gastrointestinal disorders, asthma and food allergies. The laboratory has identified and biologically characterized several critical pathways that regulate allergic responses. These discoveries include eosinophil effector mechanisms and the chemokine eotaxin/CCR-3 pathway. Current projects are:
- To elucidate the cellular and molecular processes involved in allergic responses in the gastrointestinal tract and lung using novel models of allergic responses in mice
- To test the importance of key molecule including chemokines in vivo using transgenic and gene-targeted mice that the laboratory has developed
- To biochemically characterize the signal transduction mechanism responsible for eosinophil activation
- To test the importance and blockade of these pathways in patients with inflammatory diseases such as eosinophil and hypedreosinophil syndromes
- To identify genes that predispose to eosinophil disorders.
Gurjit K. Khurana Hershey, MD, PhD
Dr. Khurana Hershey's laboratory focuses on the genetics and development of atopic diseases including asthma. The research centers on identifying atopy susceptibility genes, and dissecting the molecular mechanisms underlying the development of allergic diseases, with a specific focus on cytokine receptors and signaling pathways. Dr Khurana Hershey has built a large (>350 individuals) DNA database of well-characterized individuals with asthma. This database is utilized to evaluate genes, which may be important in the development or expression of atopic disorders. Her laboratory identified a novel allele of the IL-4 receptor alpha chain (IL-4Ra), which is an atopy susceptibility gene and correlates with asthma severity. IL-4Ra is utilized by both IL-4 and IL-13, and, thus, is critical for Th2 cell development and the induction of IgE production. Any alteration of the IL-4 or IL-13 receptor/signaling pathway might impact on the development of atopy and allergic inflammation.
Nives Zimmermann, MD
Dr. Zimmermann's laboratory is focused on genetic and biochemical characterization of the CC chemokine receptor 3 (CCR3). CCR3, the eotaxin receptor, is a major receptor involved in regulating eosinophil trafficking in allergic responses. In one set of studies, her research has shown that treatment of eosinophils with CCR3 ligands results in marked internalization of the receptor into the early endosome compartment. The mechanism and functional consequences of this ligand-induced internalization are currently under investigation.
Other experiments are aimed at delineating the regulation of CCR3 at the level of transcription. She has characterized the genetic organization of the CCR3 gene and its promoter function. Ongoing studies are aimed at elucidating the critical transcription factors and eosinophil-specific elements involved in CCR3 transcription.
Asthma is a complex chronic inflammatory disorder that involves coordinated actions of multiple pathways. In order to elucidate the interplay of these pathways, studies of gene expression profiles in a murine model of asthma using DNA microarray analysis are currently under way.
Anil Mishra, PhD
Dr. Mishra's scientific objective includes elucidating the mechanism for recruitment of inflammatory cells into mucosal allergic tissue. He is aiming to elucidate the mechanisms involved in the development of hypersensitivity responses in the esophagus and the connection between pulmonary and esophageal inflammation. He also aims to understand the mechanism of lower gastrointestinal tract allergy; in particular food related allergic responses.
Amal H. Assa'ad, MD
Dr. Assa'ad is currently conducting clinical research. Her main area of research is food allergy and asthma. Her research currently addresses the occult effect of allergic sensitization to foods on the bronchial hyperresponsiveness seen in asthmatic and the genetic basis of food allergy. She also participates in multicenter pharmaceutically sponsored research of investigational new drugs in asthma and immunodeficiencies. She is working with the basic research investigators in the division on establishing a translational research program that will bring basic research to the beside in the area of atopic and eosinophilic diseases. Her research studies include:
Michelle B. Lierl, MD
Dr. Lierl's research involves studying "A randomized trial to reduce environmental tobacco smoke exposure in children with asthma". Her role in this study is as an advisor for study design and implementation, trainer for the field staff in asthma assessments, spirometry and exhaled NO collections, and the actual measurement of exhaled NO concentrations. She is studying the usefulness of exhaled NO as a predictor of the development of post-viral asthma, in infants with bronchiolitis. She is also getting ready to embark on a study utilizing a telemedicine approach to asthma management in the school setting. Dr. Lierl is also conducting a study of the inflammatory processes in PFAPA, and the responses of PFAPA to treatment with Singulair.
How to Reach Us
For more information about the Division of Allergy and Immunology at Cincinnati Children's Research Foundation, please contact:
Katherine Henderson
Cincinnati Children's Hospital Medical Center
Division of Allergy and Immunology
MLC 2000
3333 Burnet Avenue
Cincinnati, OH 45229
Phone: 513-636-7210
Email: katherine.henderson@cchmc.org
