Our laboratory is interested in the molecular mechanisms underlying cutaneous carcinogenesis, especially melanoma. Like most malignancies, heritable risk alleles and environmental mutagenic stress conspire to drive the formation of this highly lethal skin cancer. The laboratory is fundamentally interested in three broad questions:
1. From a clinical perspective, what genetic risk factors contribute to melanoma development and how can the medical community leverage this information to manage patients?
The SCGG
(Skin Cancer Genetics Group)
houses the Harvard Hereditary Melanoma Registry, which is the largest collection of melanoma-prone families in the New England area. High-risk individuals are primarily identified through the MGH Melanoma and Pigmented Lesion Center (PLC) and the MGH Melanoma Genetics Program. DNA from eligible patients are screened for mutations in the common melanoma-predisposing loci and are also integrated into a larger consortium, GenoMEL , as part of an international effort to define new risk alleles for melanoma. In conjunction with the PLC, the SCGG is also interested in the utility of "personalized" molecular medicine in the management of melanoma patients.
2. What are the mutational targets that drive the formation of these malignant tumors?
It is clear from most cancers that somatic mutagenesis often activate proto-oncogenes or inactivate tumor suppressor genes. The patterns of these mutations often reveal important insights into the critical elements that sustain the growth of particular cancers and also novel strategies into possible molecular targets for therapy. The SCGG is interested in linear and parallel pathways that become altered during melanoma progression.
3. What is the role of ultraviolet radiation in the induction of cutaneous melanoma?
Decades of epidemiological data support a role for ultraviolet radiation (UVR), in the form of excessive solar exposure, as a behavioral risk factor for cutaneous melanoma. Despite these observations, the exact mechanisms by which UVR induces melanoma, among other skin malignancies, is not known. The SCGG is investigating both early and long-term photocarcinogenic mechanisms that are related to UVR. |
