Research Statement

Since obtaining my PhD in 1998 at the University of Illinois at Chicago, I have continuously worked in the field of structural biology and have solved the structure of more than 39 distinct proteins and protein complexes, providing unique insights into the passage of signals and compounds across the physiological membrane. I have determined the crystal structure of multiple membrane proteins and protein complexes that historically have been resistant to structure determination due to difficulties in expression, purification, protein stability and crystallization. These challenging targets include both integral membrane proteins (aquaporins, Rh proteins, ABC-transporter, GPCRs), as well as membrane associated proteins (solute receptors, F-Bar Domain). Two of the leading scientists in membrane protein crystallization have been my mentors throughout my career. I spent several years working with Dr. Wolfram Saenger who is the recipient of the prestigious Gottfried Wilhelm Leibniz Award, for the elucidation of the structure of the Photosystem II.  Dr. Andreas Engel who together with Nobel Prize winner Peter Agre performed the first structure determination of an aquaporin (AQP1). Dr. Engel brought me to Case Western Reserve University when I joined his team in 2012.

During my work in the Engel laboratory and continuing on with independent research in collaboration with Dr. Walter Boron, I have concentrated on the structure determinations of aquaporins and related integral membrane proteins, employing not only my expertise in crystallography but also cryo-EM microscopy and electron crystallography techniques.  I have solved the structure of the closed form of aquaporin-2 via 2-dimensional crystallization and electron crystallography, as well as the detergent belt of a plant aquaporin with single particle cryo-EM. During these studies, I have employed my expertise in membrane protein expression using bacterial (E. coli) and eukaryotic (S. cerevisiae, P. Pastoris, SF9 and HEK) expression systems. This has enabled me to acquire additional expertise in the purification of these membrane proteins and strategies for their stabilization and crystallization.

Currently, I am a Co-PI on the Office of Naval Research MURI collaboration (since 2016) investigating the “Molecular mechanisms and pathways for gas transport across biological membranes and implications for physiology and performance’. In this capacity, I lead the protein expression, purification and crystallization aspects of the project.  My work is closely coordinated with the research produced by the respective Boron (CWRU), Malmstadt (USC) and Tajkhorshid (UIUC) labs. During my time as Co-PI, I have independently set up and managed a membrane protein expression/purification and crystallization laboratory here at CWRU. I have trained and managed a number of research staff and students, including one postdoc, Thomas Kowatz who is now a Research Associate in the group, two Research Assistants and several Summer, Medical Physiology and Capstone students.  In addition, I am a Co-Investigator on a RBCs RO1 (Sparta Record ID: FP00238422) and am currently working with Dr. Boron and Dr. Tajkhorshid on the submission of a multidisciplinary MPI RO1 on the ‘Role of Aquaporins as Gas Channels.