Periodic Reporting for period 4 - ZF-MEL-CHEMBIO (Chemical Biology in Zebrafish: Drug-Leads and New Targets in the Melanocyte Lineage and Melanoma)
Período documentado: 2020-03-01 hasta 2022-02-28
Our work has achieved new insight into melanocyte stem cell biology. Specifically, we have identified transcriptional and metabolic pathways that are directly relevant to human melanoma. Through our small molecule screens (Aim1), we have used imaging, gene editing and chemical biology to show new regulators of stem cell pathways (Aim 2), and have directly shown that these are relevant to zebrafish and human cancer (Aim 3). Overall, these are among the first insights into the molecular mechanisms of melanocyte stem cells in zebrafish.
Our work has identified new transcriptional and metabolic regulators of melanocyte stem cells, including Tfap2b, ALDH2 and PRL3. Importantly, these findings are not simply about zebrafish melanocyte stem cells but reflect new underlying mechanisms in human skin melanocyte stem cells. Further, we find these cell states to be important in residual disease following melanoma targeted therapy. Therefore, they provide new therapeutic opportunities. This work has been published in peer reviewed journals (e.g. Cell Reports, Developmental Cell, Cell Chemical Biology, Development, Disease Models & Mechansims) and presented widely at conferences within Europe and around the world (e.g. Society for Melanoma Research, Melanoma Research Alliance, Zebrafish Disease Models Community).
As part of our work we preformed new lineage tracing technologies in zebrafish adult cancers (Travnickova et al., 2022) and developed new mechanisms to administer zebrafish drugs via pellets (Lu & Patton 2022). These are new technologies in our zebrafish community and we have already been asked for protocols and tools by many other labs.