The applicant is a Professor in the Department of Pediatrics at the University of Arkansas for Medical Sciences. This grant application addresses the qualifications of the applicant, the mentoring plan, and the patient-oriented research plan as detailed below. This grant will be utilized t provide additional protected time to be used mentoring other individuals who are pursuing patient-oriented research and working with our Departmental Clinician Scientist mentoring program. Food allergy, an IgE- mediated disease, is a significant health problem affecting 6-8% of children and 1% of adults. Peanut hypersensitivity is one of the most common and severe of the food allergies, and the only therapeutic option currently available is food avoidance. Peanuts and peanut products are used in many different processed foods, increasing the possibility of an inadvertent ingestion. Like any other allergic disease, the events that initiate and promote peanut hypersensitivity in a susceptible individual center around the response of T cells to peanut allergens The T-cell response is mediated through the T-cell receptor (TCR) which communicates with the nucleus via a complicated array of signaling pathways. It is believed that when the TCR is occupied by an allergen in susceptible individuals the signaling pathways lead to the activation of cytokine genes that promote the synthesis of IgE. Our hypothesis for this proposal is that the cascade of events that leads to T- cell activation and promotion of IgE production can be disrupted by modifying the allergen-receptor interaction. While conventional immunotherapeutic approaches have been successful for other types of allergic diseases, these approaches have not been safe or efficacious alternatives for the treatment of peanut hypersensitivity. Some problems with standard peptide immunotherapy in the treatment of peanut hypersensitivity include severe problems with standard peptide immunotherapy in the treatment of peanut hypersensitivity include severe anaphylactic reactions, lack of detailed information about the allergens, and insufficient information about the T-cell response to peanut allergens. We propose to utilize our extensive knowledge of the allergens involved in peanut hypersensitivity to design an immunotherapeutic approach that would lower the risk of anaphylactic reactions in patients with life threatening allergic reactions to peanuts.
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