Allergen Structure and Function
Asthma and other allergic diseases affect up to 30% of some populations in developed countries. The direct medical costs and societal costs (missed days in school and lost productivity at work) have a major impact on our health care system and the U.S. economy as a whole. The goal of our long-term collaborative, multidisciplinary research program is to understand the allergic process in enough detail to be able to prevent the development or effectively ameliorate allergic responses that lead to asthma and other allergic diseases. We are particularly interested in those reactions to the allergens from various plants.
Our allergy research group is applying two major approaches to explain how otherwise harmless plant protein “fool” our immune system into making vigorous but detrimental responses. The first approach consists of detailed studies of the structure of allergens to define what distinguishes them from other proteins to which we are similarly exposed. The allergenic proteins that cause mountain cedar allergy in our region (“cedar fever”) are providing an excellent model system for this approach. The second approach has been to develop an online, comprehensive, structural database of allergenic proteins (SDA) that brings together a listing of all of the known allergens (approx 800) and links these to various sources of structural information. Together these two approaches are providing new computational tools for recognizing which proteins have the potential to induce allergic responses from the human immune system.
Currently our primary treatment goal is to apply a phylogenetic approach to identify plants that produce proteins that are similar to the cedar allergens, but do not cause allergic reactions in sensitized patients. These may form the next generation of reagents for specific immunotherapy (allergy shots) with added safety and effectiveness.
With technical and intellectual support from Postdoctoral fellows: Ovidiu Ivanciuc, Ruby Tiwari, Bo Ning and Rana Bond
Phylogenetic approach to plant allergy vaccines. NIH/NIAID R01 AI52428 (Goldblum), 20% effort. Total direct cost $700,000, total cost $1,057,000. 03/04-04/08.
Cellular Response Mechanisms to Environmental Challenge. NIH/NIEHS P30 ES006676 (Halpert), Goldblum role: Associate Director for Translational Research & Director Asthma Pathogenesis Research Core. 10% effort. Total direct cost $5,282,963, total cost $7,977,276. 04/95-03/10.
Database approach for prediction of food allergenicity. FDA CFSAN-02-1 (Braun). Goldblum role: Co-inv in charge of lab-based models. 5% effort. Total direct cost $491,205, total cost $741,720, 09/02-09/06.
Structural biology of cedar pollen allergy. NIH/NIAID K08 AI55792 (Midoro) 5%. Total direct cost $440,000, total costs $475,200, 04/04-03/08.
Ivanciuc, O., V. Mathura, T. Midoro-Horiuti, W. Braun, R.M. Goldblum, and C. Schein. Detecting potential IgE-reactive sites on food proteins using a sequence and structures database, SDAP-food. J Agric and Food Chem. 51:3840-4837, 2003.
Midoro-Horiuti, T., V. Mathra, C.H. Schein, W. Braun, C.C.Q. Chin, S. Yu, M. Watanabe, J.C. Lee, E.G. Brooks, and R.M. Goldblum. Major linear IgE epitopes of mountain cedar pollen allergen Jun a 1 map to the pectate lyase catalytic site. Mol. Immunol. 40(8):555-62, 2003.
Czerwinski, EW, T. Midoro-Horiuti, M.A. White, E.G. Brooks, R.M. Goldblum. Crystal Structure of Jun a 1, the Major Cedar Pollen Allergen from Juniperus ashei reveals a Parallel ß-Helical Core. J Biol Chem. 280 (5):3740-6. 2005.
Boldogh, I., A. Bacsi, B. Choudhury, R. Alam, T. Hazra, S. Mitra, R. Goldblum, and S. Sur. ROS Generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest. 115: 2169–2179, 2005.
Midoro-Horiuti, T., C.H. Schein, V. Mathura, W. Braun, EW. Czerwinski, A. Togawa, Y. Kondo, T. Oka, M. Watanabe, R.M. Goldblum. Structural basis for epitope sharing between group 1 allergens of cedar pollen. Mol Immunol. 43:509-518, 2006..
Midoro-Horiuti, T., C.H. Schein, V. Mathura, W. Braun, EW. Czerwinski, A. Togawa, Y. Kondo, T. Oka, M. Watanabe, R.M. Goldblum. Structural basis for epitope sharing between group 1 allergens of cedar pollen. Mol Immunol. 43:509-518, 2006.
Varshney, S., R.M. Goldblum, M. Auton, C. Kearney, M. Watanabe and T. Midoro-Horiuti. Major mountain cedar allergen, Jun a 1 contains conformational as well as linear IgE epitopes. Mol. Immunol. (in press).
Togawa, A., R.C. Panzani, M. Garza, R.M. Goldblum, T. Midoro-Horiuti. Identification of a major allergen of Italian cypress pollen based on homology and cross-reactivity. (in press)