Our main project is focused on understanding pathogenesis of a rare genetic condition called Mucolipidosis type IV (MLIV). MLIV is a lysosomal storage disease, a genetic condition caused by mutations in the genes that code for components of the cellular digestive system. The resulting cellular "indigestion" causes buildup of unprocessed lipids or proteins leading to cell death and to clinical manifestations of lysosomal storage diseases such as developmental delays, movement disorders and blindness. MLIV is caused by dysfunction of an ion channel TRPML1, a pore in cellular membranes that conducts ions. Our efforts are focused on understanding what makes TRPML1 indispensable for the proper function of the cellular digestive tract. Better understanding of TRPML1 function will help uncover the mechanisms of MLIV pathogenesis and will illuminate previously unknown aspects of cell function.

Most of lysosomal storage diseases are neurodegenerative conditions. Although these diseases have been linked to cell death, it was unknown why and how lysosomal storage diseases kill cells. We developed a model of cell death that links cell death to the inability of cells affected by lysosomal storage diseases to perform housekeeping functions. This model is becoming a popular explanation for cell death and neurodegeneration in lysosomal storage diseases.

Our current research is focused on understanding how the cell gauges the functional state of its digestive tract and on the mechanisms of metal toxicity.
pittlogo © Kirill Kiselyov, 2010