As a post-doctoral fellow with Susumu Tonegawa at MIT, I contributed to the molecular cloning and characterisation of translocated c-myc genes in human Burkitt's lymphoma, and to the T cell receptor (TCR) genes. This included the unanticipated identification of the TCR gamma chain, which was followed by the discovery of the hitherto unknown gamma delta T cells. Assuming an independent Faculty position at Yale, I adopted molecular genetic approaches, including the development of key gene knockout and transgenic models, to elucidate gamma delta T cell function and development.

Those studies collectively have illuminated several areas, including:

• 'beta-selection', a point in development where gamma delta T cell differentiation diverges from the development of most alpha beta T cells.
• the demonstration that, by contrast to the systemic distribution of diverse alpha beta T cells, gamma delta T cells are disproportionately associated with epithelial tissues, wherein they reside as oligoclonal repertoires of limited diversity.
• the demonstration that gamma delta cells can promote immunoglobulin synthesis by B cells, but that this is primarily self-reactive. In 1998, I assumed the Professorship in Immunobiology at the King's College School of Medicine on the Guy's Hospital site. Our work has continued to provide insight, including:
• identification of the role played by the c-myc proto-oncogene in T cell development
• the demonstration that skin-associated gamma delta T cells protect the skin from potentially pathologic infiltrates of systemic lymphocytes
• the demonstration that gamma delta T cells are a component of the natural resistance to skin carcinogenesis.
• the demonstration that the gene expression pattern that best distinguishes gamma delta T cells from most alpha beta T cells is shared with an unusual set of tissue-associated alpha beta T cells that we collectively term unconventional T cells
• the identification of 'trans-conditioning', a mechanism by which unconventtional T cell differentiation is strongly influenced by alpha beta T cell progenitors.
• the demonstration that trans-conditioning may also affect the body's balance of effector and regulatory T cells Our current research interests focus on how repertoires of tissue-associated unconventional T cells develop and function, including the identification of novel host-encoded molecules expressed by epithelial cells with which gamma delta T cells interact. Research findings are being applied in the clinic, where we have just completed a proof-of-principle trial of gamma delta T cell therapy in hormone-refractory prostate cancer, in collaboration with F Dieli (Palermo).