Heads of Laboratories
Investigator, Howard Hughes Medical Institute
William E. Ford Professor
Laboratory of Membrane Biology and Biophysics
Cells use certain membrane proteins to pump molecules in or out of cellular structures, moving them from areas of low concentration to areas of high concentration. Dr. Chen studies a class of these proteins known as ATP-binding cassette, or ABC, transporters that power themselves using a form of chemical energy known as ATP. She is investigating ABC transporters’ role in normal cellular processes and in disease, including drug resistance.
Scientists have identified about 2,000 total ABC transporters found in all types of cells; 48 of these occur in human cells. These transporter proteins play a role in many important cellular processes, pumping an array of molecules, from nutrients to toxins and cellular building material, through the membrane bilayer. Because this molecular cargo is moving from low to high concentration, the transporter protein consumes energy.
The maltose transporter protein, a type of ABC transporter, brings a sugar known as maltose into a bacterial cell to support growth. Using x-ray crystallography, Dr. Chen and colleagues have devised a way to visualize how this transporter converts the chemical energy of ATP hydrolysis into mechanical work through a series of conformational changes.
Dr. Chen’s interests have now shifted to ABC transporters involved in the immune system and disease. For example, her lab now focuses on an ABC transporter known as P-glycoprotein. Discovered in the 1970s, P-glycoprotein plays a Jekyll-and-Hyde role in human health. This transporter recognizes an array of structurally related compounds and pumps them out of the cell. When the cell in question is cancerous and the compounds are therapies targeting some aspect of the cell’s internal machinery, P-glycoprotein’s action reduces the effectiveness of chemotherapy.
But, by doing essentially the same thing, P-glycoprotein also helps maintain the integrity of the blood-brain barrier by keeping certain types of molecules from entering the central nervous system. This function can create problems for drugs that need to get into the central nervous system.
In the long term, Dr. Chen hopes to combine structural and functional work to reveal the molecular mechanism of multidrug transporters and to develop novel reagents for chemotherapy.
B.Sc. in chemistry, 1993
Ph.D. in biochemistry, 1998
Harvard University, 1998–1999
Baylor College of Medicine, 1999–2001
Assistant Professor, 2002–2007
Associate Professor, 2007–2011
The Rockefeller University
Howard Hughes Medical Institute
Pew Biomedical Scholar, 2003
Oldham, M.L. et al. Structural basis for substrate specificity in the Escherichia coli maltose transport system. Proc. Natl. Acad. Sci. U.S.A. 110, 18132–18137 (2013).
Chen, S. et al. Carbon catabolite repression of the maltose transporter revealed by X-ray crystallography. Nature 499, 364–368 (2013).
Jin, M.S. et al. Crystal structure of the multidrug transporter P-glycoprotein from Caenorhabditis elegans. Nature 490, 566–569 (2012).
Oldham, M.L. and Chen, J. Crystal structure of the maltose transporter in a pretranslocation intermediate state. Science 332, 1202–1205 (2011).
Oldham, M.L. and Chen, J. Snapshots of the maltose transporter during ATP hydrolysis. Proc. Natl. Acad. Sci. U.S.A. 108, 15152–15156 (2011).