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Our scientific engine is fueled by three independent, yet related, syngergies: the Massachusetts General Hospital Melanoma and Pigmented Lesion Center (PLC) and the Wellman Center for Photomedicine.
It has become clear over the past decade that melanoma, like many other cancers, develops as a result of heritable or acquired variants in the melanocyte genome. We are thus interested in both the genetics of melanoma predisposition and the genetics of melanoma progression. There are currently several major lines of investigation in our research enterprise.
In collaboration with the Center for Cancer Risk Assessment, we have collected over 160 melanoma-prone families from around the world and have characterized the germline status of these families for known moderate and high risk melanoma loci including CDKN2A, CDK4, MC1R and ARF. In collaboration with GenoMEL (www.genomel.org), we are also searching for novel risk alleles through both candidate resequencing approaches and whole genome association studies (GWAS).
Our close connection to melanoma patients through the Massachusetts General Hospital PLC allows us to translate these basic findings into clinical research. We have, and are continuing to, develop mathematical models to predict genotype based on phenotype information. Personalized medicine remains a mission codified by the Human Genome Project, and yet, the utility of molecular diagnostics remains uncertain. The PLC is one of the few melanoma units in the world that offers genetic counseling as part of its research and clinical outlets.
Through the Wellman Center for Photomedicine- the worlds largest laboratory dedicated to the study of light-tissue interactions and light-based medicine- we are also honing in on the molecular mechanisms that explain the long-held observation of excessive UVR exposure and melanoma risk. We are interested in developing both in vitro and in vivo models of UVR melanoma genesis so as to better resolve the underlying events which lead to melanoma emergence.
Over the years, we have also been committed to understanding the pathways which dictate melanoma progression. There appears to be at least two critical genetic nodes that are frequently altered for melanocytes to fully transform into cancer- CDKN2A/p53/CDK4 and RAS/BRAF/PTEN. These configuration of genetic changes at these loci speak to unique vulnerabilities for melanocyte carcinogenesis and potential targets for therapy.
View a list of publications by researchers at the Tsao Laboratory
Wellman Center for Photomedicine
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