Our research focuses on the biology of melanocytes, the cells that
pigment the skin, eyes, and hair. One major emphasis of the lab is the
study of uveal melanoma, the most common intraocular cancer, which
arises from melanocytes in the eye. Uveal melanoma has no effective
treatment options in metastatic cases. With our colleagues, we
identified the first oncogenes that drive uveal melanoma formation in
people: GNAQ and GNA11. These two closely related heterotrimeric G
protein alpha subunits are mutated in a mutually exclusive pattern in
most cases of uveal melanoma. Our lab engineered the first GNAQ knock-in
mouse model, which expresses the oncogenic version of GNAQ in a
tissue-specific manner. When directed to melanocytes, the mice develop
the same subset of melanocytic lesions that bear GNAQ mutations in
humans. This mouse model will be be useful for understanding the
signaling pathways downstream of GNAQ in melanoctyes and testing new
therapeutic agents. We are also interested in how melanocytes develop,
particularly how the different developmental lineages of melanocytes
contribute to the diversity of melanoma subtypes. Several projects are
underway to understand how metalloproteases shape the extracellular
matrix around melanocytes, regulating growth and cell migration during
various developmental and postnatal stages.