Our Research
Where Genetics Meets Culture: Research Rooted in Science and Respect
We are a team of quantitative and qualitative scientists dedicated to conducting research with Indigenous communities.
Themes in our work:
Pharmacogenomics
Our lab looks at how a person’s genes affect how they respond to medications. For example, we aim to create personalized and culturally-tailored healthcare strategies to improve nicotine cessation outcomes in American Indian and Alaskan Native communities.
Bioethics
We believe research should be done with communities, not on them. Our lab focuses on the ethical side of genetics—like how DNA is used and how people are involved in research—especially when working with Indigenous peoples.
Evolutionary Genetics
We study how genes have changed over time, including genes passed down from ancient Ancestors and relatives like Neanderthals and Denisovans. This helps us understand how evolution affects traits like how people respond to medicine today.
Explore a few of our latest projects:
Featured Project
Insights into pharmacogenetics, drug-gene interactions, and drug-drug-gene interactions
This review explores genetic contributors to drug interactions, known as drug-gene and drug-drug-gene interactions (DGI and DDGI, respectively). This article is part of a mini-review issue led by the International Society for the Study of Xenobiotics (ISSX) New Investigators Group. Pharmacogenetics (PGx) is the study of the impact of genetic variation on pharmacokinetics (PK), pharmacodynamics (PD), and adverse drug reactions. Genetic variation in pharmacogenes, including drug metabolizing enzymes and drug transporters, is common and can increase the risk of adverse drug events or contribute to reduced efficacy. In this review, we summarize clinically actionable genetic variants, and touch on methodologies such as genotyping patient DNA to identify genetic variation in targeted genes, and deep mutational scanning as a high-throughput in vitro approach to study the impact of genetic variation on protein function and/or expression in vitro. We highlight the utility of physiologically based pharmacokinetic (PBPK) models to integrate genetic and chemical inhibitor and inducer data for more accurate human PK simulations. Additionally, we analyze the limitations of historical ethnic descriptors in pharmacogenomics research. Altogether, the work herein underscores the importance of identifying and understanding complex DGI and DDGIs with the intention to provide better treatment outcomes for patients. We also highlight current barriers to wide-scale implementation of PGx-guided dosing as standard or care in clinical settings.
Featured Project
Genetic research within Indigenous communities: Engagement opportunities and pathways forward
Against a historical backdrop of researchers who violated trust through lack of benefit sharing, transparency, and engagement, efforts are underway to develop better approaches for genetic and genomic research with Indigenous communities. To increase engagement, there is a need to understand factors that affect researcher and community collaborations. This study aimed to understand the barriers, challenges, and facilitators of Indigenous Peoples in the United States participating in genetic research. We conducted 42 semistructured interviews with Tribal leaders, clinicians, researchers, policy makers, and Tribal research review board members across the United States to explore perceived risks, benefits, barriers, and facilitators of genetic research participation. Participants, identifying as Indigenous (88%) or non-Indigenous allies (12%), described their concerns, hesitancy, and fears about genetic research, as well as the roles of trust, transparency, and respect for culture in facilitating partnerships. Previous harms—such as sample and data misuse, stigmatization, or misrepresentation by researchers—revealed strategies for building trust to create more equitable and reciprocal research partnerships. Participants in this study offered strategies for increasing genetic research engagement. The pathway forward should foster transparent research policies and practices to facilitate informed research that supports the needs and priorities of participants, communities, and researchers.
Featured Project
Pharmacogenetic variation in Neanderthals and Denisovans and implications for human health and response to medications
Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes—genes responsible for the processing of exogenous substances such as food, pollutants, and medications—as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.
