The overarching goal of this K01 proposal is for the candidate to acquire the expertise necessary to lead a research program in environmental epidemiology applied to immune-mediated disorders. Dr. Somers is trained as an epidemiologist, with significant expertise in the clinical epidemiology of lupus, public health surveillance of chronic disease, and descriptive epidemiology of autoimmune diseases. Immediate career goals are to expand on this background by acquiring comprehensive training in relevant areas in environmental health sciences, including molecular epidemiology, immunotoxicology, and epigenetics. Long-term career goals are to unravel the etiologies of autoimmune and other immune-mediated disorders, an in particular, to identify the role of potentially modifiable early life exposures. The proposed training and research will be conducted under the mentorship of Howard Hu, M.D. MPH Sc.D. and Bruce Richardson, M.D. Ph.D. Dr. Hu is a recognized leader in environmental epidemiology and health effects of heavy metals. Dr. Richardson is a rheumatologist and immunologist, and has performed groundbreaking laboratory research related to epigenetics and lupus. The Career Development Plan will include both structured and informal learning activities that together will provide in depth training in the following growth areas for the candidate: (a) Environmental health science and molecular epidemiology, including exposure assessment, gene-environment interactions, and immunotoxicology;(b) developmental and maternal-fetal immunology;(c) assessment and interpretation of biomarkers of immune phenotype and function;(d) epigenetics methods, including DNA methylation, related to health and human disease. The proposed research will be a birth cohort study investigating the association between early life heavy metal exposure and immune dysregulation. The study population will be the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohort (PI: Dr. Hu), which has been extensively characterized in terms of heavy metal exposures, including mercury (prenatal and childhood measurement). This proposal will be the first to investigate immunologic endpoints in this birth cohort. Emphasis will be exploration of the association between in utero and early childhood exposure to mercury and immune perturbations, which may be relevant in terms of autoimmune and allergic disease. Immune parameters will include auto-antibodies, cytokines, and gene-specific methylation levels relevant to T helper cell differentiation. Balance of Th subsets is important in directing host immune responses, and clearly influenced by microbial stimuli. This project addresses a critical gap in knowledge in the role of non-microbial exposures in immune modeling, and will represent a significant career enhancement opportunity for the candidate.
Autoimmune diseases have a major impact on quality of life, and as a group, are among the 10 leading causes of death among young and middle-aged women. Mercury is a pervasive environmental toxicant with suggested links to autoimmunity. This project will investigate the impact of early life mercury exposure on the developing immune system, to determine the timing and levels of exposure that may have adverse health consequences which should be accounted for when establishing public health policy.
|Littlejohn, E; Marder, W; Lewis, E et al. (2018) The ratio of erythrocyte sedimentation rate to C-reactive protein is useful in distinguishing infection from flare in systemic lupus erythematosus patients presenting with fever. Lupus 27:1123-1129|
|Somers, Emily C; Marder, Wendy (2017) Infertility - Prevention and Management. Rheum Dis Clin North Am 43:275-285|
|Somers, Emily C; Monrad, Seetha U; Warren, Jeffrey S et al. (2017) Antinuclear antibody prevalence in a general pediatric cohort from Mexico City: discordance between immunofluorescence and multiplex assays. Clin Epidemiol 9:1-8|
|Marder, Wendy; Littlejohn, Emily A; Somers, Emily C (2016) Pregnancy and autoimmune connective tissue diseases. Best Pract Res Clin Rheumatol 30:63-80|
|Berman, D; Clinton, C; Limb, R et al. (2016) Prenatal Omega-3 Supplementation and Eczema Risk among Offspring at Age 36 Months. Insights Allergy Asthma Bronchitis 2:|
|Thomas, Deena B; Basu, Niladri; Martinez-Mier, E Angeles et al. (2016) Urinary and plasma fluoride levels in pregnant women from Mexico City. Environ Res 150:489-495|
|Strickland, Faith M; Patel, Dipak; Khanna, Dinesh et al. (2016) Characterisation of an epigenetically altered CD4(+) CD28(+) Kir(+) T cell subset in autoimmune rheumatic diseases by multiparameter flow cytometry. Lupus Sci Med 3:e000147|
|Marder, Wendy; Knight, Jason S; Kaplan, Mariana J et al. (2016) Placental histology and neutrophil extracellular traps in lupus and pre-eclampsia pregnancies. Lupus Sci Med 3:e000134|
|Housey, Michelle; DeGuire, Peter; Lyon-Callo, Sarah et al. (2015) Incidence and prevalence of systemic lupus erythematosus among Arab and Chaldean Americans in southeastern Michigan: the Michigan Lupus Epidemiology and Surveillance Program. Am J Public Health 105:e74-9|
|Marder, Wendy; Vinet, Évelyne; Somers, Emily C (2015) Rheumatic autoimmune diseases in women and midlife health. Womens Midlife Health 1:|
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