Regulation of Membrane Trafficking
Eukaryotic cells such as yeast, plants, and humans use conserved pathways to direct small membrane-bound vesicles containing specific cargo to discrete subcellular compartments and to the plasma membrane for secretion. Proper navigation of these vesicles through the dense cytosol of the cell is crucial for normal growth, maintenance of cellular integrity, organelle biogenesis, and intercellular signaling events, such as release of hormones, cytokines and neurotransmitters. Disruption of these trafficking pathways has been implicated in a variety of humans diseases, including immune disorders, cancer, diabetes, ciliopathies, and viral and bacterial pathogenesis. Our lab is interested in elucidating the mechanistic details of vesicle delivery to better understand how specificity is maintained in complicated cellular environments, and how errors in trafficking can give rise to disease phenotypes.
Our overall research goals are to delineate molecular mechanisms that underlie fundamental cell biology processes of membrane transport, including exocytosis, endocytosis and nuclear export. Elucidation of these mechanisms requires multidisciplinary approaches, combining protein and lipid biochemistry, biophysics, structural biology (both X-ray crystallography and state-of-the-art cryoEM), mass spectrometry and integrative computational approaches, fluorescence microscopy, and genetics and cell biology in a variety of model organisms.
A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis.
Author(s): Shah RK, Munson M, Wierenga KJ, Pokala HR, Newburger PE, Crawford D