Our model systems
Our lab uses three preclinical model systems: in vivo (mouse model), ex vivo (3D organoids) and in vitro (cell lines). All three systems have their pros and cons; however, they are interdependent and complementary approaches to studying human disease and understanding complex biological phenomena. Our team maximizes the benefits of our model systems to rigorously address our questions and hypotheses. Nevertheless, it remains true that human disease is best studied in human subjects. Thus, whenever we discover new findings using our model systems, we verify them in human samples or human populations. Additionally, the opposite case can occur where we test observational studies from human (i.e. epidemiological studies) using our model systems to understand causality and mechanisms. Ultimately, our goal is to provide the solid preclinical results that warrant investigation in therapeutic and preventative human clinical trials.
In vivo Mouse models
Our lab uses various mouse models of colorectal cancer depending on the purpose. This includes genetically engineered mouse models (APC, KRAS, BRAF, PIK3CA, p53), xenografts, PDX (patient-derived xenografts), orthotopic organoid transplantation in mice, and chemically induced mice models such as Azoxymethane (AOM) mice.
Ex vivo Organoids
Three-dimensional (3D) cultures of organoids from normal cells or tumor cells are emerging model systems that hold great promise to mimic better the biology found in vivo. To complement our mouse models, we utilize this surrogate organoid ex vivo approach to facilitate the molecular characterization and functional assays using powerful genetic approaches such as shRNA or CRISPR in a time and cost-effective manner. Furthermore, utilizing an organoid system allows us to discern the direct effect of nutrients on normal intestinal cells or tumor cells from cell non-autonomous effects caused by nutrient-host interactions. Our lab uses both healthy intestinal and tumor organoids derived from mice and humans.
In vitro cell lines
Monolayer cancer cell lines derived from cancer patients have been a pillar of cancer research and gave us many significant insights in the field of cancer biology despite their limitations (e.g. the adaptation of cell lines to monolayer culture conditions). Our lab continues to exploit the benefits of in vitro cell line systems to address our research questions.
Technologies that we use
To unravel the complex relationship between diets and intestinal cells, we need tools that can measure our biological changes in high-throughput and systematic manners. Thankfully, we have many cutting-edge technologies that enable us to explore these diverse and dynamic interactions. Our laboratory utilizes –omics technologies such as next-generation sequencing (genomics, transcriptomics, microbiome), proteomics, and metabolomics together with traditional molecular, genetic and biochemical assays. We integrate these -omics data to understand the role of diets in our body and disease progress in holistic and comprehensive ways.