The overall goals of the Yale SPORE in Skin Cancer (YSPORE) are to improve prevention, diagnosis and treatment of melanomas. One of the overriding themes of the YSPORE is to reveal biomarkers and targets for therapy based on information from Next-Generation (Next-Gen) DNA sequencing, genomics and proteomics analyses. This approach will be used to identify: a) regions of the genome that are sensitive indicators of long-term accumulation of DNA damage and mutations resulting from sunlight exposure (Project 1); b) The molecular diversity of melanomas and response to targeted therapy (Project 3); and c) The RAC1 pathway as a target for melanoma therapy (Project 4). Project 2 is dedicated to one of the most promising immunotherapy for melanoma, anti PD-1, and is focused on tumor/stroma interactions to reveal mechanism of evasion of cancer immunity. We will use structure-function analyses to identify druggable targets in resistant cells and in a novel RAC1 pathway that we have identified in melanoma. The expected translational outcomes of the program are: 1) Development of biological indicators for sun exposure risk to be used in melanoma prevention; 2) The identification of predictive biomarkers for therapeutic blockade of the PD-1/PD-L1 pathway and the role of this pathway in resistance to other types of immunotherapy, leading to potentially more effective combination immunotherapy; 3) The development of molecular tests that will guide treatment for BRAF inhibitors; 4) The classification of melanoma according to therapeutic options based on mutations in ‘driver’ pathway; 5) identification of small molecule that can target the “RAC1 pathway”; 6) The implementation of new national initiatives such as the CaTISSUE, The Cancer Genome Atlas (TCGA) and the MRF National Consortium for melanoma clinical trials.
Developmental Research and Career Development Programs provide funds for one or two years for new investigators who wish to join the research on skin cancer. There are Biospecimen Resource and Bioinformatics/Biostatistics Cores that support the translational research needs of all investigators in the YSPORE.
The Specimen Resource Core provides reagents to non-YSPORE investigators as well.
The core provides:
- Primary cultures of normal human melanocytes and fibroblasts from newborn foreskins;
- Melanoma cells;
- Primary and immortalized mouse melanocytes;
- Genetically modified mouse melanocytes;
- Advice and hands-on training for the growing of cells especially those that have so far proven fastidious, such melanocytes from primary melanomas from the radial growth phase.
- Specialized media for melanocytes
Request should be addressed to Antonella Bacchiocchi who is the manager of the Specimen Resource Core.
The co-directors of the YSPORE are Ruth Halaban, Mario Sznol, and Robert Tigelaar. The co-leaders of the various projects are Douglas Brash, Michael Krauthammer, Yossi Schlessinger, Titus Boggon, Harriet Kluger, Marcus Bosenberg, Peter Peduzzi, Shuangge Ma, Lieping Chen, and Xiaopan Yao. The dedicated surgeons are Drs. Steve Ariyan and Deepak Narayan that keep providing the specimens needed for the studies.