Amanda J. Lea

Vanderbilt University
2022 Scholar

Research Interests

Environmental determinants of health: molecular mechanisms and inter-individual variation

People who are exposed to social, nutritional, or physical stressors during development experience lifelong increases in the risk of most non-communicable diseases (NCDs). However, the mechanisms that allow early life experiences to “get under the skin” to impact long-term health are poorly understood. At the genomic level, this phenomenon is thought to be mediated by a class of environmentally sensitive molecules—known as gene regulatory mechanisms—that control the degree to which each gene is turned “off” versus “on” in a cell. However, because gene regulatory mechanisms are sensitive to environmental inputs throughout the entire life course, it has been challenging to disentangle early versus later life effects. This problem is especially acute because most genomic studies 1) are purely correlational/observational and 2) are focused on high income countries, where people experience relatively similar environments throughout their lives. 

To address this gap, I work with subsistence-level groups experiencing rapid, within-generation lifestyle shifts as a result of globalization, urbanization, and socioeconomic change. More specifically, as part of large, collaborative, and community-engaged projects, I work with Turkana pastoralists in Kenya, Tsimane horticulturalists in Bolivia, and Batek hunter-gatherers in Malaysia. In each of these locations, my team and I collect interviews to understand early life experiences, biological samples to study gene regulatory mechanisms, and health data to understand individual NCD risk. Importantly, because socioeconomic change is happening so quickly in all of these countries, our studies encompass extreme between-community and within-individual variation in early life experiences. I also complement this field-based, observational work with lab-based experiments capable of testing for causal connections between different gene regulatory processes. By working “in the field” and “in the lab”, my goal is to go beyond correlations to pair an understanding of human variation and biology with evaluation of causal mechanisms. 

In summary, I aim to uncover how our bodies remember early life experiences and how these memories affect our lifelong risk of disease, especially “lifestyle” diseases such as obesity, type II diabetes, and cardiovascular disease. While there is widespread agreement that globalization, urbanization, and socioeconomic change are responsible for rising rates of NCDs worldwide, little work has tackled the contribution of life course experiences to the problem. By doing so, I hope to improve our understanding of the developmental origins of health, as well as provide insight into the health challenges facing low- and middle-income countries.

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