My research falls under the broad umbrella of molecular anthropology, with a particular focus on population history, human and pathogen evolution, and what could be described as microbial anthropology.
During my tenure at the University of Oklahoma (OU), it has been my objective to foster leadership in research that bridges microbial and anthropological sciences. The study of human microbiomes (or human microbiota) has begun an integration into traditional branches of biological anthropology, including primatology, paleoanthropology, bioarchaeology, and human biology. We are beginning to understand that microbes, such as bacteria and viruses, are an essential part of what it means to be biologically human.
I could not be happier with our wonderful success in research. I have led research featured in several news outlets including Science Magazine, Discover Magazine, National Geographic news, New Scientist, and more. I have published in high impact journals, including Nature Genetics, Nature Communications, Proceedings of the National Academy of Sciences, Current Biology, PLoS Genetics, and others. My research has been supported by NSF (including a CAREER award), NIH (including three R01s and a “Center for Excellence” grant), and other agencies. But my research is a team effort, and I am fortunate to be a contributor to an amazing group of scientists (LMAMR.ORG).
Bridging Research Themes
Ancestral state of human microbiome, pathogens, and antibiotic resistance – It is now well accepted that human microbiomes are actively involved in human health and that changes in our gut microbiomes from living more sanitized, industrialized, lifestyle have led to susceptibility to certain metabolic and autoimmune disorders. My research has made significant contributions in determining what exactly has changed during industrialization by characterizing the ancestral state of the human ecology through studies that include microbiome information from ancient and traditional peoples, and non-human primates. This work has evolved to projects that characterize the evolution of pathogens and antibiotic resistance.
Health disparities and ethics – Early human microbiome research was popularized by a clear association between gut microbiome composition, diet, and metabolic and inflammatory disorders. One of the most pronounced health disparities in the U.S. is the rate of chronic metabolic and inflammatory conditions among socioeconomically vulnerable groups, such as obesity and type 2 diabetes among some Native American and African American communities. However, the ethical inclusion of potentially socioeconomically vulnerable participants within biomedical research is challenging, in particular, when that biomedical research remains on the frontier of science, with many unknowns that may impose risks to participants. Nevertheless, the exclusion of diverse groups within such frontier biomedical science may exacerbate health disparities by unintentionally shaping the downstream medical interventions to favor some groups over others. My research heavily considers the ethical inclusion of the socioeconomically vulnerable within biomedical research.
Innovating research in ancient biomolecules – I lead, and/or contribute to, a wide range of ancient biomolecule research that includes ancient DNA from human remains as well as the study of ancient microbiomes and meta-proteomes through the analysis of coprolites and dental calculus. My lab published the first ancient human microbiome study to include a taxonomic analysis and metabolic functional potential (Tito et al. 2008); this is the same year the NIH Human Microbiome Project was announced. This research continued with an assessment of challenges in characterizing microbiomes from coprolites (Tito et al. 2012). I have fostered a research group that is at the forefront of research in ancient biomolecules. In 2014, I was a critical member of an extraordinary study that was led by my postdoctoral fellow, which revealed that ancient dental calculus harbors a human oral microbiome rich genomic and proteomic information (Warinner et al. 2014). This study was partially funded by my NIH R01 grant (GM089886); Discover Magazine ranked the study in the top 100 discoveries of the year. Currently, I serve as the co-PI for an NSF grant that continues to explore the limits of ancient DNA from dental calculus (NSF: BCS1516633), and I continue to contribute to publications related to ancient DNA research (Ziesemer et al 2016, Ozga et al 2016, Warinner and Lewis 2015, Warinner et al 2015).
Extant human microbiome diversity and extirpated bacteria – Much of my lab-based research focuses on the microbiome variation of indigenous people. I lead research that partners with extant traditional peoples, which includes novel data from hunter gatherers and rural agriculturalist (Obregon-Tito et al 2015); my research has revealed a group of commensal/mutualistic bacteria that have been lost in industrialized populations. One particular strain of these bacteria are most closely related to taxa known to digest fiber and produce anti-inflammatory metabolites, which is quite suspicious considering the transition to industrialization has also been classically connected to a rise in inflammatory disorders. This research continues with an awarded renewal to my NIH grant (2 R01 GM089886, 2016-2020), which will include partnerships with traditional peoples in the Americas and Africa.
My study of human associated microbes is not limited to molecular approaches, but also includes traditional microbial isolation and morphological characterization. Through my studies of archaeological fecal material, my lab has demonstrated that ancient parasites can be individually isolated and morphologically characterized prior to being DNA sequenced (Cleeland et al 2013), which is a technique that had previously never been accomplished on ancient material. Moreover, in collaboration with a chemotaxonomist, our team has discovered novel bacteria taxa. We recently published a novel genus, Ezakiella peruensis (Patel et al 2015), and novel species Clostridium amazonense (O’Neal et al 2015) and Peptoniphilus catoniae (Patel et al 2016), from our study of the indigenous Peruvian gut, which included samples provided by traditional peoples, such as hunter-gatherers. We have discovered a number of other novel organisms that are in preparation for publication. Furthermore, our research is expanding into a detailed study of the resistome (Omics of antibiotic resistance), which includes molecular data (genomes, proteomes, and metabolomes) and cultivation experiments to record the degree of ancestral antibiotic resistance (2 R01 GM089886).
Ethical, Legal and Social Implications – My research integrates Omics research with ethical perspectives. I was a consortium member of the National Institutes of Health’s Human Microbiome Project. Our research included exploring the Ethical Legal and Social Implications (ELSI) of Human Microbiome work with indigenous communities (R01 HG005172). Our engagement with indigenous communities often includes detailed discussions about what are microbiomes, how are they characterized, and why they have been of interest to biomedical scientists. From my experience, even the most remote indigenous groups have an underappreciated understanding of the environment that is easily translatable to the scientific understanding of ecosystems and the evolutionary concepts of natural selection and fitness, which provides a path for mutual sharing ideas about microbes, microbial ecosystems and health. To facilitate this discussion, we have brought microscopes into the field to better explain the science of microbiology to the collaborators. Included within our objectives was to understand the concerns and perceptions of various indigenous groups in their understanding their own microbiomes as well as microbiomes of potential ancestors. In this sense, we are conducting embedded ELSI research, that is, the study of ELSI issues as they manifest from an ongoing investigation. Such a research design provides a unique perspective on ethical concerns that are grounded in actual scientific research. In 2016, I serve as a co-PI on a newly awarded Center for Excellence in ELSI research (CEER) by the NIH (RM1 HG009042), increasing my momentum in this area.
Biomedical research – Bridging off my human biological diversity projects has been a current growth in more biomedically focused research. Most advanced in this area has been our partnership with the Cheyenne and Arapaho (C&A) tribes. Originally, the partnership began as part of our ELSI engagements discussed previously (R01 HG005172). After three years of focus groups and survey studies regarding the microbiome, the C&A tribal health board and tribal governance agreed to include C&A participants in a human microbiome/metabolome biodiversity project. This was particularly important considering that much of the baseline human microbiome literature were studies with Euro-Americans from metropolitan areas. The product of this C&A partnership was the first gut microbiome study conducted in partnership with American Indian tribes (Sankaranarayanan et al 2015) as well as a similar oral microbiome study (Ozga et al 2016). Within this human biodiversity project was the discovery of a microbial and metabolite composition common to the C&A participants that was largely consistent with that reported in metabolic disorders. In partnership with the C&A, we have expanded this research into a clinical study that will more deeply explore the underlying biology of obesity and Type 2 Diabetes in the C&A using both metagenomics, transcriptomics, and metabolomics.
I have fostered several new biomedical pilot projects, largely funded by locally available grants. This includes the “Ovarian Cancer Microbiome Project”, funded by the OU’s Stephenson Cancer Center, which is tracking oral, skin, vaginal, and gut microbiome changes longitudinally, through diagnosis, treatment and recovery of ovarian cancer. Such a study may reveal paths to reduce ovarian cancer risk, and/or mitigate side effects of ovarian cancer treatment, such as neuropathy. Similarly, I have early stage partnerships with Oklahoma researchers exploring pregnancy and tobacco, lupus, Sjorgren’s syndrome, stroke, and reproductive disorders. While at an early stage, each of these partnerships have progressed to a stage in which microbiome data has been collected.
Population genetics – I frequently publish in areas of human population dynamics and human evolution. In 2007, my colleagues and I published a detailed genome-wide study of genetic variation in Native Americans (Wang, Lewis, Jakobsson et al 2007); I share the first author position in this study. In 2015, this publication was named among the top 10 of all articles published in PLoS Genetics. More recently, I have contributed to studies that consider the role of evolutionary forces and population dynamics in shaping human variation (Schlebusch et al 2013, d’Alpoim Guedes et al. 2012). I led a study that assessed putative ancestral ties for an unmarked African American slave cemetery (Ozga et al 2015), and I was a contributing author to biogeography studies in Peru (Cabana et al 2014), North America (Ozga et al 2016) and the Himalayan Arc (Jeong et al 2016), and a new study tracking the origin of dairying (NSF: BCS1523264, role co-PI).
Laboratories of Molecular Anthropology and Microbiome Research (LMAMR.ORG) – Rather than continuing the trend in the U.S., where “lone wolf” molecular anthropologists struggle to build a research empire around them, I proposed a faculty consortium, a shared directorship, of multiple faculty. I envisioned a group of molecular anthropologists with similar research objectives, each capable of leading their own independent research, but also each fitting seamlessly in larger team science approaches. Through shared resources, the faculty can leverage state of the art facilities and greatly expand research momentum. From this vision, we have created LMAMR. We address classic anthropological genetic questions, with the added twist of including the human microbiome within the definition of human biology. In the fall of 2016, LMAMR now harbors five tenure-track faculty and a state of the art six chambered ancient DNA laboratory, placing OU in a leadership position in molecular anthropology in the U.S. Within LMAMR, I lead NIH and NSF grant funded research, but LMAMR is much bigger than any single faculty member.
The Center on the Ethics of Indigenous Genomic Research (CEIGR) – In the Spring of 2016, my collaborators and I were awarded an NIH Center for Excellence in ELSI Research (CEER). Serving as one of the PIs, this center partners with two of the leading tribal health care systems in the country (the Chickasaw Nation in Oklahoma and Southcentral Foundation in Alaska), among other groups. It is well recognized that substantial controversy exists between genomics and American Indian and Alaska Native communities. Using a community based approach, this center facilitates the discussion of what role genomic knowledge serves for tribal health systems. Our goal includes the development of a consortium of tribal and community-based institutions on ELSI research and an education program centered on these themes.
Consolidate Core Laboratory (CCL) – I am a founding member of OU’s core laboratory for genomics. The CCL centralizes existing advanced technology genomics instruments and equipment for access by the broader OU research community and includes support staff for laboratory management and bioinformatic pipelines.
Center for Microbial and Anthropological Sciences at OU (MASOU) – I am directing a new center that serves as a support mechanisms for other research groups and centers to facilitate and foster team science. MASOU will house an administrative assistant, bioinformatics research faculty, data management technician, and laboratory technician to better bridge research between multiple OU centers, such as those described above, as well as others lead by collaborators.
Over the next five years, I will help foster OU’s strength in molecular anthropology, microbial anthropology, ethics and ancient biomolecule research. In my own research, I am aggressively integrating proteomics and metabolomics, which I believe to be poised to dramatically change our understanding of human biology. Moreover, I hope to be a leader in bringing these technologies to health disparity research in culturally appropriate ways.