The cell must be instructed to stay alive — if there is no such signal for growth, it will undergo programmed cell death even when placed in a nutrient-rich environment. Not surprisingly, the control of growth signaling is frequently hijacked during tumorigenesis to promote tumor formation, drug resistance, or metastasis. The Chang Lab focuses on signal transduction mediated by members of the Ras GTPase superfamily. Mutations affecting Ras and Ras pathways are among the most frequent genetic changes in human cancers. These Ras proteins cycle between the GDP and GTP bound states to act as binary switches to regulate a wide range of signal transduction pathways, the most important of which for cancer the signaling from the growth factors. Currently our lab is pursuing two lines of research with the ultimate goal of uncovering therapeutic opportunities for cancers:
(1) There are three highly similar RAS genes in mammals, but they are differentially mutated in cancers of different tissues. We have evidence that Ras proteins are not created equal — they signal from different cell compartments to control different sets of activities. Thus one active area of research in our lab is to tease out the mechanisms regulating Ras trafficking in the cell in and possibly prevent them from reaching the final destination.
(2) While RAS mutations are very common in some cancers, e. g., 90 percent of the pancreatic cancers have RAS mutations, RAS mutations are very rare in breast cancer, which affects one in eight women in the United States. In collaboration with bioinformaticians and physician scientists, we have evidence that increasing activities from wild type Ras plays a critical role in promoting the progression of breast cancer and resistance to therapy. This is a critical research direction for the lab that can have an immediate impact on the patients to save many lives.