Research
Yan’s lab has committed to taking the challenge of understanding how gut microbes may contribute to disease initiation and progression and using this understanding to change the way that we diagnose and treat patients, particularly extreme cases in patients with colorectal cancer and lung cancer. To defect this deadly disease, we need to better understand every aspect of its causes: what are the risk factors, and how does it form and spread. We also need to uncover the link between the characteristics of tumor microenvironment and the different ways in patients’ response to treatment. Our research projects have three broad objectives:
Primary Research Interests:
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Epidemiological risk factors correlate of the cancer microbiome
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The role of microbiome in cancer therapeutic response
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Assembly and dynamics of gut microbiome in host ecological microenvironment
1. Epidemiological risk factors correlate of the cancer microbiome
We are integrating metagenome profiling with machine learning approaches to unveil the influence of lifestyle and environmental factors on the microbiome in large scale investigations of human populations. We expect to have far-reaching implications in the field of hypothesis-driven microbiome discovery, forward from the correlative studies based on large-scale population cohorts. The gut microbiome has been linked to CRC, but the causal alterations that may precede CRC have not been clearly elucidated. In one of our previous works, I led the analysis and assessed microbiome changes prior to colorectal neoplasia and determined potential causality of early microbial changes in CRC. This study demonstrates the feasibility of monitoring Lynch patients using non-invasive, microbiome-focused methods and to disaggregate early-stage, potentially causal changes associated with the development of neoplasia from microbiome responses that correlate with CRC and its associated treatment.
Highlighted publications:
- Yan Y, Drew DA, Markowitz A, Lloyd-Price J, Abu-Ali G, Nguyen LH, Tran C, Chung DC, Gilpin KK, Meixell D, Parziale M, Schuck M, Patel Z, Richter JM, Kelsey PB, Garrett WS, Chan AT, Stadler ZK, Huttenhower C. Structure of the mucosal and stool microbiome in Lynch syndrome. Cell Host & Microbes. 2020. PMID: 32240601.
- Yan Y, Nguyen LH, Franzosa EA, Huttenhower C. Strain-level epidemiology of the human microbiome. Genome Medicine. 2020. PMID: 27098841.
2. The role of microbiome in cancer therapeutic response
The biological importance and varied metabolic capabilities of specific microbial strains has long been established. We already know how pathogenic strain variants are detrimental to human health, but the disease consequences of more subtle genetic variation in the microbiome have only recently been exposed. Our lab has several collaborations with Shanghai medical teams and study the role of microbial strains during cancer immunotherapy. We are developing computational algorithm and statistical modeling to investigate how the tumor microbiome influence the impact of or shaped in cancer patients receiving novel cancer therapy. These will provide multiple opportunities for potential translation into the clinic through the development of novel diagnostics and therapeutics that target microbes to improve cancer treatment efficacy, and ultimately facilitate the personalized medicine in public health.
Highlighted publications:
- Yan Y. The microbial code and cancer immunotherapy outcome. Cell Host & Microbe, 2023. PIMD: 37442095
- Spencer C. et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. PMID: 34941392.
- Yan Y, Nguyen LH, Franzosa EA, Huttenhower C. Strain-level epidemiology of the human microbiome. Genome Medicine. 2020. PMID: 27098841.
3. Assembly and dynamics of gut microbiome in host ecological microenvironment
Loss of biodiversity can have significant consequences for ecosystem processes. However, the relative contribution of host characteristics to the process of microbial community assembly at different functional levels is not yet known, such as tumor microenvironment. We are developing experimental approach such as Dilution-seq and PMA-seq methodology to achieve different levels of complexity of possible microbial inoculum to study the role of diversity and activity in community assembly and environmental filtering of bacterial community assembly. We also combine experimental approaches for direct visualization of host-microbe interactions in the tumor microenvironment and functional validation in vivo model systems.
Highlighted publications:
- Yan Y, Kuramae EE, de Hollander M, Klinkhamer PGL, Van Veen JA. Functional traits dominate the diversity-related selection of bacterial communities in the rhizosphere. ISME J. 2017. PMID: 27482928.
- Yan Y, Klinkhamer PGL, Van Veen JA, Kuramae EE. Environmental filtering: A case of bacterial community assembly in soil. Soil Biology and Biochemistry, Volume 136, September 2019, 107531.IF 7.2 Web of science.