A Systems Biology Approach to the Tumor Microenvironment Using Zebrafish

ASPIRE Award (2019-2020)

Richard White, MD, PhD, Memorial Sloan Kettering Cancer Center

Understanding how cancer cells interact with non-cancer cells is key to developing treatments that prevent the initiation of metastasis. Currently, model systems that allow researchers to observe and study these interactions in vivo are limited. Dr. Richard White and his group at Memorial Sloan Kettering Cancer Center are developing a zebrafish model to visualize cancer metastasis. Because zebrafish are transparent, the interaction of tumor cells with other cells in their microenvironment can be visualized. To create an accurate representation of human cancer, the team is conducting single-cell and spatial transcriptomic analysis of human tumor specimens and using the knowledge gained to recapitulate the metastatic ecosystem in zebrafish. Building upon the transparency of the organism, the team is using fluorescence imaging of the entire tumor microenvironment as well as CRISPR technology to alter different mediators in the microenvironment to determine which have functional significance. The results of this work will lead to a better understanding of how cancer cells interact with normal tissue cells and potentially uncover new therapeutic targets for preventing or inhibiting cancer cell metastasis.

published research

Baron M, Tagore M, Hunter MV, Kim IS, Moncada R, Yan Y, Campbell NR, White RM, Yanai I. The Stress-Like Cancer Cell State Is a Consistent Component of Tumorigenesis. Cell Syst. 2020.

Lumaquin D, Johns E, Montal E, Weiss JM, Ola D, Abuhashem A, White RM. An in vivo reporter for tracking lipid droplet dynamics in transparent zebrafish. Elife. 2021.

Hunter MV, Moncada R, Weiss JM, Yanai I, White RM. Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface. Nature Commun. 2021.