Kirill Kiselyov

Research in our lab is focused on the integrative function of the cell – its ability to gauge the functional status of its components and work as a complete, coordinated system. As a model system we use lysosomal storage diseases: a set of genetic conditions resulting from mutations in genes coding for components of the endocytic pathway or caused by chemical inhibition of the lysosomal function. The endocytic pathway is a cellular digestive tract. Its compartments sort, digest and absorb food, remodel cellular membranes and recycle cellular components. When it malfunctions, products of cellular “indigestion” accumulate inside the cell causing cell death, which manifests clinically in developmental delays and abbreviated lifespan.

This link between the cellular digestive activity and cell death illustrates complex communications between the cellular components. We think that cells monitor and respond to changes in the functional status of the endocytic pathway. Furthermore, it is likely that such cellular responses may contribute to the disease pathogenesis. Towards understanding how cells respond to cues from the endocytic pathway, we are screening changes in gene expression and protein profiles induced by genetic ablation of endocytic components or by inhibition of the lysosomal function by toxic metals. Molecular candidates identified as a result of such screens provide key information regarding cellular response networks and identify possible candidates for pharmacological interventions into conditions caused by lysosomal and, perhaps other abnormalities.