Spatio-temporal functional characterization of melanoma stem cells

Our preliminary findings demonstrate that melanoma growth is hierarchically organized by a population of melanoma stem-like cells (MSCs), which reside in a perivasular niche and exhibit a transcriptomic signature of pre-migratory neural crest cells established transiently during embryonic development.  Metastatic dissemination is, instead, driven by a "mesenchymal-like" subpopulation, which preferentially accumulates at the invading front of primary lesions.  With this application, we propose to chart dynamics and functional 4D maps (space and time) of the evolving melanoma ecosystem, and thereby visualize tumor state transitions in the in vivo relevant context.  We aim to dissect the functional contribution of these cell states to growth and metastasis, define the cellular composition of the niches in which they reside and identify tumor-host interactions that modulate cell state transition.  I anticipate that this effort will lead to the development of effective therapeutic approaches that intercept the disease before its lethal spreading to vital organs.