Current Status: GRAD
Graduate Department: Epidemiology
Other Degrees: BA in History, Yale University;
Advisor(s): Juan Leon, PhD MPH;
Hometown: Denver, CO
I rock climb, bike, and am occasionally found singing along with church-organ karaoke at Sister Louisa's.
Background: Noroviruses (NoV) are the most common cause of acute gastroenteritis in the United States and Europe and are responsible for over 50% of all epidemic gastroenteritis worldwide. Though infection in adults is generally self-limiting, NoV infection can have severe consequences for children, the elderly, and the immunosuppressed. Despite this widespread impact, human NoV immunology is poorly understood because of the lack of an efficient cell culture system or small animal model for human NoV. There is no commercially available treatment or vaccine for NoV, making greater understanding of the immunology of this common cause of morbidity a research priority. Study Goals/Objectives: The overall goal of this dissertation is to elucidate the acute human serum cytokine response and its relationship with the pathogenesis and symptoms of NoV infection. To accomplish this, we will conduct descriptive analyses and identify immunologic correlates of protection, symptoms, and viral shedding. This goal is subdivided into three aims. Aim 1: Describe temporal trends in serum cytokines following human NoV challenge. Aim 2: Identify baseline and early cytokines predictive of infection. Aim 3: Identify associations between cytokines and disease course. Aim 3 is subdivided into two sub-aims examining a) symptoms and b) viral shedding. Methods: Study design: The study has two components: one, nested case-control study based on a prospective cohort study of individuals experimentally challenged with NoV; and two, a follow-up study of cases and controls to determine subsequent outcomes. Serum samples from baseline and the first four days post-challenge have been analyzed for immunologic biomarkers. Population: Of the 64 total healthy adults who participated in the NoV challenge studies, 26 became infected following challenge. They have been pair-matched by age to 26 of the volunteers who did not become infected following challenge. Data collection: Demographic, clinical, symptom, and fecal NoV shedding data was collected as part of the original study. For this dissertation, serum samples from baseline and the first four days following challenge (five time points per subject) have been analyzed for the concentration of 16 cytokines and chemokines. Analysis: The data in this study will be analyzed using quantile regression, mixed effects models, principal component analysis, and survival analysis. Potential Impact: Overall, there is a lack of understanding of NoV immunology, and modeling approaches based on data from human challenge studies present an opportunity for improving knowledge of NoV pathogenesis and human resistance to NoV infection. The results of this study will help elucidate key associations between the immune response to NoV and clinical outcomes, helping guide vaccine development, clinical practice, and surveillance.
Leadership in MD/PhD Program: Class Representative