Doctoral Dissertation Research: Social and environmental influences on inflammation

这个博士论文研究项目调查了社会和环境因素如何通过炎症过程产生压力“进入皮肤”，以影响影响生命过程中健康的生物学结果。慢性炎症可能是疾病的原因或征兆，炎症反应是健康状况不佳的前兆，并为了解疾病发作提供了见解。该项目有助于更清楚地了解社会和环境因素如何作为诱导炎症的机制，将压力与疾病联系起来。通过集中分析生物标志物C反应蛋白（CRP）的变化，一种经过充分验证的炎症生物标志物，与环境和心理社会压力指数的变化有关，本研究的结果有助于更好地确定压力，炎症，环境驱动因素和生物结果之间联系的基础。这是一个以社区为中心的项目，为参与者提供研究培训，并为这一新兴领域的未来研究奠定基础。表观遗传途径在整个生命中充当社会因素和疾病风险之间的通道，表观遗传修饰可以影响炎症反应。在面向临床的研究中，与人类健康相关的结果变化通常被分为普查级别的类别，这些类别可能无法提供关于理解人类生物学变化的信息。阐明环境信息和潜在相关的表观遗传修饰的证据可以提供对整个因果关系途径（从机制到结果）的变异的更细致入微的理解。该项目旨在1）了解社交及其他环境因素的变化如何与人群内和人群间CRP浓度的变化相关，以及2）了解社会和环境因素如何影响与应激生理学和应激反应相关的基因组区域的甲基化。综合起来看，该项目产生的结果可以促进对环境和生活经验转化为生物结果的潜在机制的理解，并为有关进化和贸易的理论框架提供信息。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值进行评估来支持和更广泛的影响审查标准。

This doctoral dissertation research project investigates how social and environmental factors that create stress ‘get under the skin’ through the process of inflammation, to influence biological outcomes that impact well-being over the life course. Chronic inflammation can be a cause or sign of disease, and inflammatory responses are precursors of poor health outcomes and offer insights into understanding disease onset. This project contributes to a clearer understanding of the ways in which social and environmental factors serve as mechanisms that induce inflammation, linking stress to disease. By focusing analysis on variation in the biomarker C-reactive protein (CRP), a well validated biomarker of inflammation, in relationship to variation in indices of environmental and psychosocial stress, the results of this study can contribute to better identifying the underpinnings of the links between stress, inflammation, environmental drivers, and biological outcomes. This is a community-centered project which provides research training to participants and sets the foundation for future research in this emerging area. Epigenetic pathways act as channels between social factors and disease risk throughout life, and epigenetic modifications can impact inflammatory responses. In clinically oriented research, variation in outcomes related to human health is often grouped into census-level categories that may not be informative with respect to understanding human biological variation. Incorporating environmental information and evidence of potentially linked epigenetic modifications can offer a more nuanced understanding of variation across the full pathway of causation, from mechanism to outcome. This project aims to 1) understand how variation in social and other environmental factors relates to variation in CRP concentrations, both within and across populations, and 2) to understand how social and environmental factors influence methylation in areas of the genome related to stress physiology and stress response. Taken together, results generated from this project can advance understanding of the underlying mechanisms involved in the transduction of environmental and lived experience to biological outcomes and inform theoretical frameworks regarding the evolution and trade-offs involved in these mechanisms within and across human populations.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.