Drug Discovery for the control of vesicular trafficking mechanisms in cellular processes of medical importance
Intracellular vesicular transport is essential for nearly all aspects of cellular physiology and plays a central role in the regulation of cellular homeostasis, cell division and immunity. Most vesicular transport processes are regulated by Rab proteins, monomeric GTPases of the Ras superfamily that act as membrane organizers. Different Rab proteins are distributed in specific cell compartments and, together with their effectors, synchronize and regulate vesicle motility, docking and fusion to specific acceptor membranes.
My laboratory is interested in the study of Rab GTPases and effector molecules and their role in trafficking mechanisms. In our studies, we utilize animal models and cellular systems with the common objective of elucidating the role of small Rab GTPases in physiology and disease. In addition, we have developed unique quantitative systems biology methods for the analysis of granule dynamics and positioned ourselves as one of the few laboratories studying the processes that control vesicular trafficking mechanisms preceding exocytosis in granulocytes.
We are also interested in vesicular trafficking mechanisms associated with human disease, and as part of this work we have developed and implemented high-throughput screening assays to identify small-molecule inhibitors and activators of vesicular trafficking and found specific modulators that will be utilized to answer mechanistic questions and to explore in vivo effects associated with clinically relevant processes including inflammation and sepsis, diabetes, AMD, lysosomal storage disorders and endocytic pathway-associated processes including viral entry and phagocytosis. The results of our research should uncover the molecular mechanisms regulating vesicular transport and lead to effective strategies for the treatment of human disease.