Eric Chang Lab
Ras GTPases are biologically active when they are GTP-bound and inactive when they are GDP-bound. In response to cell signals, Ras proteins cycle between the GDP and GTP bound state, thus acting as binary switches that regulate a wide range of biological functions.
Ras proteins play key roles in deciding whether a cell should divide or remain dormant or differentiate into another cell type. As the cancer cell frequently must tamper with these same programs that are controlled by Ras, mutations affecting Ras activities are among the most common genetic alterations in human tumors—approximately 30 percent of all human tumors contain ras mutations, and in some tumors, such as colon and pancreatic tumors, frequencies of ras mutations are as high as 50 and 90 percent, respectively.
The Chang Lab, located in the Alkek Building, is pursuing two major goals to better understand how Ras controls tumorigenesis.
- Our first major endeavor is to identify novel Ras effectors, which are downstream targets controlled by Ras to regulate growth and differentiation. We are currently focusing on the Cdc42 pathway, which interacts with Int6, a potential tumor suppressor for breast cancer formation. Our results support a model in which Int6 can control tumor formation by regulating the functioning of the 26S proteasome, which acts to degrade mitotic regulatory proteins to ensure normal cell division control and chromosome stability. Our second project focuses on the fact that the human Ras pathways are very complex. There are four structurally similar Ras proteins that in vitro can activate many known Ras effectors; however, in vivo these Ras proteins appear to control different functions.
- Our second major goal is to decipher how a given Ras protein can selectively activate a particular effector to specifically control tumor formation. Our current model suggests that a given Ras protein can control different functions by signaling from different cell compartments, so that a Ras pathway functioning in one cell compartment can transform cells much more efficiently than that in another compartment.
We carry out these studies using modern molecular and genetic tools in a range of model organisms. We use the power of yeast genetics to efficiently identify new components whose functions are evolutionarily conserved, while mammalian cells, particularly breast cancer cells, are the ultimate arenas where our models can be tested.
Eric C. Chang, Ph.D. also teaches several courses and a briefly description of what they are can be found here. Read more about Eric C. Chang, Ph.D.
We have an open lab design to allow efficient use of equipment and space and to better foster interaction between scientists of diverse disciplines. Dr. Chang also is a member of the Molecular and Cellular Biology department, which ranks second in the nation as the most-well funded academic department, and the Cell and Molecular Biology graduate program.