Somatic mutations drive phenotypic changes in cellular behaviors. Mutations to cancer causing tumor driver genes may be acquired years, if not decades before clinical diagnosis of cancer. What happens to the cell and how collective tissue behaviors shape the trajectory of a lethal cancer during a prolonged occult tumorigenic phase is a great mystery. Our lab has developed a set of mouse tools for illuminating the earliest initiation phase of cancer. Our primary objective is to map the cellular events and biochemical interactions at work during the initiation phase of cancer in order to discover strategies for the prevention or treatment of lethal cancers. We use the mouse to fluorescently barcode somatic mutations and then observe cell competition, cell adaptation, and tumorigenesis in vivo. Our current focus is three-fold:
Building fluorescent-barcoded mice for visualizing cancer initiation
We have developed Cancer rainbow mice (Crainbow) in order to visualize the effects on cells immediately after oncogene expression. For a full description of Crainbow see our publication in Nature Communications or read our blog article posted to “Behind the Paper” on Nature Cancer Community.
Our goal is to use Cancer rainbow mice for measuring cell competition (or maybe even cooperation) during the occult tumorigenic phase of cancer. All Crainbow models (8 and counting) are immune intact and enable us to study emergent cell behaviors in the presence of a normal immune response. We are also working toward imaging modalities and registration techniques for overlaying of histopathology and lineage tracing data (i.e. “TruRegistry”).
Intestinal stem cell competition in vivo and ex vivo
How do somatic mutations spread throughout the intestine? We recently showed that this can happen one of two ways, either during a postnatal growth phase of the intestine or through oncogenesis of microenvironmental cues (i.e. Rspondins). Read more here and see one of our favorite images from the study below.
Imaging three-dimensional cellular networks during cancer progression
Our lab is recently interested in mapping the cellular behaviors and networks present during the initiation of breast cancer. New protocols for clarifying whole-organoids are being used in our Crainbow mice so that we can three-dimensionally map cell competition during the developmental phase of the mammary gland. Here, is one such movie of a three-dimensional projection of premalignant growth in the mammary gland – stay tuned, more progress in the mammary gland is coming soon!
The Snyder lab is part of the Department of Surgery’s Division of Surgical Sciences and affiliated with the Center for Applied Therapeutics. We have a secondary affiliation with the Department of Cell Biology and are also members of the Development and Stem Cell Biology (DSCB) and Cell and Molecular Biology (CMB) training program, as well as the Duke Cancer Institute.
- Crainbow in the news as a "Biomedical Picture of the Day"
Routine technologies and tools used by the Snyder lab include hyperspectral fluorescent microscopy, whole-organ imaging, genetic engineering, stem cell biology, mouse models, bioinformatics, scRNAseq, and lineage tracing. The Snyder lab has their own 7-laser, hyperspectral, laser scanning confocal for imaging all day and all night.
Are you interested in imaging, mouse genetics, and discovering how cancer cells are born? We need cancer biologists, molecular biologists, and bioinformaticians interested in all things imaging/big data. We are always looking to grow our team, including a post-doctoral fellowship, graduate student training, technical position, or undergraduate research opportunity. Send us an email.
Want to collaborate or have a reagent request? We like to share and support team science. Send us an email.