This career development award will provide Jessica Savage, MD, MHS with the necessary experience and training to become an independent investigator in Allergy and Immunology. The prevalence of allergic diseases such as asthma, food allergy, eczema, and hay fever has risen dramatically in recent decades in the United States. The reasons for these high rates of allergy are largely unknown, but are generally thought to be due to environmental exposures. In light of the growing evidence that disruption of the human microbiota-the mutualistic and commensal organisms that live within us- is associated with allergic disease, it is notable that the increase in allergy followed the widespread introduction of personal care products containing antimicrobial chemicals (triclosan and parabens), which were invented over 40 years ago. Dr. Savage's previous work demonstrated a novel association between these antimicrobial chemicals and allergy. In this proposal Dr. Savage will further explore the association between antimicrobial chemicals and allergy in young children (Aim 1), determine the source of exposure to these chemicals in children (Aim 2), and determine the effects of these chemicals on the human microbiome and gene expression, likely intermediates in their association with allergy (Aim 3). Dr. Savage will build on her previous formal training in epidemiology and develop expertise in the development of cohort and interventional studies, exposure assessment, and analysis of high-throughput genetic data, and contribute to our understanding of why allergy develops. Dr. Savage's career trajectory demonstrates a commitment to patient-oriented research. Her previous studies demonstrated that children with food allergy are taking far longer than previously assumed to outgrow their common childhood food allergies and that anti-IgE is rapidly effective for many, but not all patients with food allergy. With this proposal, Dr. Savage broadens her interest beyond food allergy and will study factors that influence the development of all allergic diseases. This research has the potential to lead to simple and effective strategies for the prevention of allergic disease. Dr. Savage's research will take place at the Channing Division of Network Medicine (CDNM) at Brigham and Women's Hospital. The CDNM is a leader in epidemiologic studies world-wide and her section has over 30 faculty investigators and 110 other research personnel. Dr. Savage will be mentored by Dr. Litonjua, a genetic epidemiologist with expertise in exposure assessments and microbial-disease associations. Her scientific advisory committee includes Dr. Diane Gold, an epidemiologist with experience with birth cohort studies and allergy development; Dr. Scott Weiss, a genomic epidemiologist with expertise in network analyses applied to allergic respiratory disease; and Dr. Russ Hauser, an environmental epidemiologist with expertise in the effects of environmental chemicals on human health. They have many years of experience mentoring junior faculty and are committed to Dr. Savage's long term goals of becoming a successful independent investigator.

Public Health Relevance

Allergic disease (eg. asthma, food allergy, eczema, and hay fever) are major public health problems that are increasing in prevalence for unclear reasons. This proposal tests the hypothesis that prenatal and early life exposure to the antimicrobial chemicals triclosan and parabens found in commonly used personal care products (eg. toothpaste and lotions) influence the development of the immune system and the risk of allergic disease. This study has the potential to lead to effective prevention strategies to reduce the risk of allergy.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Mentored Patient-Oriented Research Career Development Award (K23)
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Allergy, Immunology, and Transplantation Research Committee (AITC)
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Gondre-Lewis, Timothy A
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Brigham and Women's Hospital
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Lee-Sarwar, Kathleen; Hauser, Russ; Calafat, Antonia M et al. (2018) Prenatal and early-life triclosan and paraben exposure and allergic outcomes. J Allergy Clin Immunol 142:269-278.e15
Savage, Jessica H; Lee-Sarwar, Kathleen A; Sordillo, Joanne et al. (2018) A prospective microbiome-wide association study of food sensitization and food allergy in early childhood. Allergy 73:145-152
Savage, Jessica; Johns, Christina B (2015) Food allergy: epidemiology and natural history. Immunol Allergy Clin North Am 35:45-59
Cardet, Juan-Carlos; Johns, Christina B; Savage, Jessica H (2015) Bacterial metabolites of diet-derived lignans and isoflavones inversely associate with asthma and wheezing. J Allergy Clin Immunol 135:267-9