Johns Hopkins School of Medicine

The cell biology of secretory protein synthesis

The focus of my research is to understand the cell biology of secretory protein synthesis. Specifically, I use a combination of live cell imaging, biophysical fluorescence methods, biochemistry, and molecular biology to study the regulation, organization and dynamics of secretory protein translocation and folding in cells. Cutting edge quantitative fluorescence microscopy methods including FRAP, FLIP, photoactivation and FRET reveal information about protein mobility, environment, protein complex size, protein-protein interactions, and membrane dynamics in living cells. The endoplasmic reticulum (ER) is the largest eukaryotic organelle and carries out multiple functions including: 1) secretory protein bio-synthesis, and export 2) protein glycosylation and disulfide bond formation. To prevent protein misfolding, the ER contains a variety of proteins, termed chaperones. A functional secretory protein must be successfully translocated into the ER and then interact with the correct subset of chaperones to correctly fold. Failure of any one of these steps can lead to protein-misfolding diseases, such as cystic fibrosis. At the same time, regulation of these processes can be exploited by viruses, such as HIV, and appears to be important in genetic diseases such as polycystic liver disease. My current focus has been to optimize fluorescent proteins and biosensors for use in cellular environments other than the cytoplasm. The folding environments of many cellular organelles are quite distinct and can promote misfolding or misregulation of fluorescent proteins that were originally developed for use in the cytoplasm.

In addition to my research, I serve as the Director of Student and Postdoctoral Programs at Janelia Research Campus. If you are interested in learning about how to apply for faculty positions, I have written a free eBook on the topic and it is available here:  http://blog.addgene.org/tips-for-getting-a-faculty-position