Frank McCormick, PhD, FRS
Director, UCSF Helen Diller Family Comprehensive Cancer Center
Associate Dean, UCSF School of Medicine
David A. Wood Distinguished Professorship of Tumor Biology and Cancer Research
My research is focused on signal transduction pathways in cancer cells, and ways of treating cancer based on these pathways. The Ras pathway has been my primary interest, although we are also interested in metabolic differences between cancer cells and normal cells, and defects in cancer proteins related to mitotic checkpoints. My lab is attempting to understand how oncogenic Ras alters cell growth and survival in cancer cells, and in cells from patients suffering from neurofibromatosis. The latter disease is caused by loss of a negative regulator of Ras of the Ras GAP family, a family of enzymes that was discovered in my lab. Loss of the neurofibromin protein leads to hyperactivation of Ras in cells of neural crest origin: as a result patients expressing defective neurofibromin suffer from learning defects, multiple benign lesions and an increased risk of certain cancers. We are using a combination of yeast genetics and biochemistry to understand more about the function of neurofibromin and how it is regulated, as well as new ways of treating this terrible disease.
The Ras pathway is negatively regulated by intrinsic pathways that are not well understood, including those involving ephrins and sprout proteins. We are using biochemical methods to elucidate these pathways at the molecular level, and hope that this will lead to new ways of blocking Ras activity for therapeutic purposes.
My lab has worked extensively on viruses that kill cancer cells selectively. We are developing this concept using self-amplifying plasmids that replicate in cancer cells specifically, and encode proteins that kill neighboring cancer cells. Plasmid amplification is driven by DNA replication proteins coded by the plasmid itself, and an origin of DNA replication also encoded in the plasmid. The replication protein has been modified to prevent amplification in normal cells, in which RB and p53 block activity.