Geoffrey Chang

Geoffrey Chang is an associate professor at The Scripps Research Institute in La Jolla, California, United States. His laboratory focuses on the structural biology of integral membrane proteins, particularly exploring X-ray crystallography techniques for solving the tertiary structures of membrane proteins that are notoriously resistant to crystallization. The laboratory has specialized in structures of multidrug resistance transporter proteins in bacteria. In 2001, Chang was awarded a Beckman Foundation Young Investigator Award, designed to support researchers early in their academic careers, for his work on the structural biology of multidrug resistance.

Chang and coauthors published papers on the structures of two multidrug resistance transporters, known as EmrE, MsbA, and NorM between 2001 and 2010. Although the initial structures were widely considered puzzling in the field due to their unexpected placement of their ATP binding sites in the assembled dimer, the publication of an additional structure in the same protein family indicated that the Chang structures were unlikely to represent the biologically active conformation of the molecules. Chang and coauthors issued retractions of their structural papers on EmrE, MsbA and NorM, citing an error in an internal software utility as the source of the data misinterpretation that led to the appearance of wrongly assembled dimers. The application of a popular protein structure validation tool to one of the retracted MsbA structures results in scores that indicate severe errors in this structure.

Since that time, however, Chang has published other papers in the field of structural biology, and has been awarded a EUREKA grant, "for exceptionally innovative research projects that could have an extraordinarily significant impact on many areas of science," from the National Institutes of Health.

Retracted papers
The following papers were retracted in 2007:
 * Chang G, Roth CB. (2001) Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293(5536):1793-800. PMID 11546864
 * Pornillos O, Chen YJ, Chen AP, Chang G. (2005) X-ray structure of the EmrE multidrug transporter in complex with a substrate. Science 310(5756):1950-3. PMID 16373573
 * Reyes CL, Chang G. (2005) Structure of the ABC transporter MsbA in complex with ADP.vanadate and lipopolysaccharide. Science 308(5724):1028-31. PMID 15890884
 * Chang G. (2003). Structure of MsbA from Vibrio cholera: a multidrug resistance ABC transporter homolog in a closed conformation. J Mol Biol 330(2):419-30. PMID 12823979
 * Ma C, Chang G. (2004). Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli. Proc Natl Acad Sci USA 101(9):2852-7. PMID 14970332

Recent work
In 2009, Chang published a paper in Science, describing a protein that keeps certain substances, including many drugs, out of cells. The protein, called P-glycoprotein or P-gp for short, is one of the main reasons cancer cells are resistant to chemotherapy drugs. In 2010, he led a study published in Nature detailing the structure of the MATE (Multi antimicrobial extrusion protein) family transporter NorM, which belongs to a member of the only remaining class of multidrug resistance transporters left to be described by scientists. The work has implications for combating dangerous antibiotic resistant strains of bacteria, as well as for developing hardy strains of agricultural crops.