Candidate: The applicant, Terumi Midoro-Horiuti, M.D., Ph.D., is an Assistant Professor in the Department of Pediatrics at the University of Texas Medical Branch (UTMB). Dr. Midoro completed her residency in pediatrics, her clinical fellowship in allergy/immunology in Japan, research fellowship in Child Health Research Center at the University of Texas Medical Branch. Dr. Midoro and her supervisors at the University of Texas Medical Branch realize additional training in structural and molecular biology will enhance Dr. Midoro's transition into independent investigator. Sponsor: Her mentor, Randall Goldblum, M.D. is a Professor in the Department of Pediatrics and Human Biological Chemistry and Genetics and a Director of Child Health Research Center. Co-mentor, Werner Braun, PhD. is a Professor in the Department of Human Biological Chemistry and Genetics and a Senior Scientist of the Sealy Center for Structural Biology. ? Career Development Plan: The educational goal Dr. Midoro proposes here is to learn the theory and practice of structural biology through course work and an investigation of the mechanisms of allergen recognition and allergic sensitization. During the first two years Dr. Midoro will take formal courses: Structure and Function of Biomolecules, and Bioinformatics tools on the Web supported by the Department of Human Biological Chemistry and Genetics. She will devote 80% of her time to her training and her research project. The hypothesis that will be tested by the proposed studies is that conformational IgE epitopes are structurally different from epitopes recognized by other isotypes and are, at least in part, responsible for the allergenicity of certain proteins.
The specific aims that will test the hypothesis are to: (1) Identify conformational IgE and IgG epitopes by probing a phage display peptide library. (2) Identify critical elements of linear and conformational epitopes by comparing structures of sensitizing allergens with those of their phylogenetic homologues. (3) Design epitope mimics (mimotopes) of Jun a 1 epitopes that prevent IgE binding and cross-linking by allergens. Child Health Research Center and Searly Center for Structural Biology at the UTMB provide an ideal environment for training Dr. Midoro by incorporating expertise from diverse fields. Completion of this project should greatly enhance Dr. Midoro's chances of an independent research carrier. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI055792-04
Application #
7214696
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Prograis, Lawrence J
Project Start
2004-04-01
Project End
2008-07-31
Budget Start
2007-02-01
Budget End
2008-07-31
Support Year
4
Fiscal Year
2007
Total Cost
$121,262
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Pediatrics
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
Goldblum, Randall M; Madagoda-Desilva, Rumali S; Zhang, Yueqing et al. (2018) Molecular patterns in the isotype-specific antibody responses to the major cedar aeroallergen Jun a 1. Mol Immunol 101:527-530
Goldblum, Randall M; Ning, Bo; Judy, Barbara M et al. (2016) A single mouse monoclonal antibody, E58 modulates multiple IgE epitopes on group 1 cedar pollen allergens. Mol Immunol 74:106-12
Goldblum, Randall M; Ning, Bo; Endsley, Mark A et al. (2014) IgE antibodies to mountain cedar pollen predominantly recognize multiple conformational epitopes on Jun a 1. J Allergy Clin Immunol 134:967-9.e7
Midoro-Horiuti, Terumi; Goldblum, Randall M (2014) Epitope mapping with random phage display library. Methods Mol Biol 1131:477-84
Midoro-Horiuti, Terumi; Goldblum, Randall M (2014) Epitope mapping with membrane-bound synthetic overlapping peptides. Methods Mol Biol 1131:421-6
Tiwari, Ruby; Negi, Surendra S; Braun, Benjamin et al. (2012) Validation of a phage display and computational algorithm by mapping a conformational epitope of Bla g 2. Int Arch Allergy Immunol 157:323-30
Liu, Zun; Bhattacharyya, Shikha; Ning, Bo et al. (2010) Plant-expressed recombinant mountain cedar allergen Jun a 1 is allergenic and has limited pectate lyase activity. Int Arch Allergy Immunol 153:347-58
Ivanciuc, Ovidiu; Midoro-Horiuti, Terumi; Schein, Catherine H et al. (2009) The property distance index PD predicts peptides that cross-react with IgE antibodies. Mol Immunol 46:873-83
Moehnke, Marcie H; Midoro-Horiuti, Terumi; Goldblum, Randall M et al. (2008) The expression of a mountain cedar allergen comparing plant-viral apoplastic and yeast expression systems. Biotechnol Lett 30:1259-64
Varshney, Shikha; Goldblum, Randall M; Kearney, Christopher et al. (2007) Major mountain cedar allergen, Jun a 1, contains conformational as well as linear IgE epitopes. Mol Immunol 44:2781-5

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