Dr. Greene has defined the basic principles
of both the assembly of erbB receptor ensembles relevant to cell
growth and transformation and how to disable these transforming
growth factor receptor complexes. His early work led to the identification
of the neu receptor protein on transformed as well as normal
neural and secretory epithelial cells. Greene demonstrated that
disabling the oncoprotein receptor complex with ectodomain binding
monoclonal antibodies or small molecules could reverse phenotype
from a malignant one to a more normal one. These principles led
to the creation of "herceptin" which is now routinely
used to treat neu driven human tumors.
Greene went on to define the basic principles of how the oncoprotein
receptor assembles into a dimer/oligomer as a consequence of
a (negative charge) point mutation in the transmembrane region.
The role of charge in the transmembrane has now been found to
be a general organizing feature of many multiunit receptors.
His studies identified a physical association between the neu
protein and the closely related normal EGF receptor leading to
a hetero-oligomeric assembly. Greene defined this process which
led to the acquisition of new signalling and affinity features
of the heteromeric receptor complex. The heterodimerizaiton process
was found to be a common feature of this receptor family and
explained the general principle of how monomorphic receptors
could diversify their signaling repertoire by associating with
other discrete monomorphic family members.
As a leader in structurally based approaches to understand receptor
function, he has designed and created new small compounds that
have important potential for many clinical applications in cancer
and other areas.
