Virtual Oral Presentation Australasian Society for Dermatology Research 2022 Annual Scientific Meeting

The White lab is interested in the intersection between developmental biology and cancer biology. We primarily utilize the zebrafish as a model, along with hPSC models with the Studer lab. Melanoma initiation requires establishment of a permissive neural crest program typified by SOX10 AND crestin. We found that a large number of chromatin-modifying genes like ATAD2 are expressed at a higher level in the neural crest compared to melanocytes, which endows them with competence for the SOX10 program4. We have also shown that this varies across anatomic space, in which specific oncogenes are more permissive in body vs. acral sites due to a synergy with limb-specific HOX13 genes. We have additionally shown mechanisms that allow a cell to attain metastatic capacity. One way this occurs is via heterotypic cell-cell interactions between cells with distinct transcriptional states6. We have also shown that the microenvironment influences these gene programs to promote progression and metastasis. For example, adipocytes act as lipid donors to the nascent tumor, which  act as both signaling molecules but are also a major metabolic source of acetyl-CoA, leading to widespread changes in histone acetylation and chromatin architecture. These observations lead to the idea that the microenvironment can drive metastasis via changes in both metabolism and epigenetic state of the cancer cell.