Downward's research investigates
cancer biology. His work on the
Ras GTPase has made seminal contributions to our understanding of how cellular signal transduction pathways are subverted in
oncogenic transformation. His work provided the first demonstration that
Guanosine triphosphate-loading on Ras, which is commonly mutationally activated in
human tumours, is normally regulated in response to extracellular factors; he went on to characterise
growth factor receptor complexes mediating Ras
nucleotide exchange, and to demonstrate that GTP-bound Ras binds to and activates the
RAF kinase, which controls the
mitogen-activated protein kinase pathway. Julian was first to demonstrate that
phosphoinositide 3-kinase (PI 3-kinase) is also a Ras effector, important in regulation of apoptosis. He showed that transformation by Ras requires interaction with multiple effectors, which contribute differentially to
cell cycle progression,
cytoskeletal regulation and
apoptosis. His work has established that both cell matrix and cell–cell interaction activate the PI 3-kinase/
PKB pathway, and thereby prevent
programmed cell death, and that it is activation of this pathway by
oncogenic Ras that allows anchorage-independent growth of transformed cells. Most recently he has focused on identifying unique weaknesses of cancer cells expressing the activated Ras oncogene using a combination of large-scale functional genomics and pre-clinical models of lung cancer. ==Awards and honours==