Our laboratory uses a unique combination of

genetics, biochemistry and advanced microscopy

to understand the molecular mechanisms underlying fundamental lysosome biology, primarily using baker's yeast (S. cerevisiae) and its vacuolar lysosome as models.

 Our claim to fame is the discovery of the IntraLumenal Fragment (ILF) pathway, a genuinely new cellular protein degradation process that selectively down-regulates lysosomal nutrient transporters. When two lysosomes fuse, they first dock together with the underlying fusion machinery assembling into a ring. Unneeded or damaged transporter proteins embedded their membranes are selectively sorted into the encircled area, called the boundary membrane. Upon lipid bilayer merger (fusion), apposing boundaries merge and form a protein-laden ILF entrapped within the lumen of the fusion product (a single large lysosome) where it is exposed to acid hydrolyses and degraded.

We are now focused on understanding how this ILF pathway contributes to maintenance of organelle identity and integrity, to remodeling protein and lipid landscapes observed during cell aging programs, and to total cell proteostasis and metabolism.