Yiannis Ioannou, PhD

Specific Clinical/Research Interest: Molecular genetics

Summary of Research Studies:
Our lab is involved in a number of projects that center on the biology, function and diseases of the endosomal/lysosomal (E/L) system. In addition, we are developing methods to treat lysosomal diseases via enzyme and gene therapy approaches. See our website for details. Some brief examples of our work are given below: Subcellular Cholesterol/lipid Transport. Although the intercellular transport of cholesterol from the liver to peripheral tissues has been intensively studied, little is known about its egress from the E/L system, its intracellular transport and the proteins involved in this process. The existence of such proteins is highlighted by the autosomal recessive disorders, Niemann-Pick C (NPC) disease, in which cholesterol accumulates in lysosomes and leads to progressive neurodegeneration and Tangier disease in which cholesterol efflux at the plasma membrane is defective. Our overall objective is to identify and characterize the various components of the intracellular cholesterol and lipid transport machinery and determine their function and interactions. Proteomics of the E/L system. Cell Proliferation and Apoptosis: It is becoming clear that the lysosome has a greater role in cellular processes than was originally proposed. Our studies focus on the isolation and purification of intact endosomes and lysosomes. These organelles are then characterized for their membrane composition to identify novel, membrane proteins. We have established a novel method for the isolation and characterization of endosomes and lysosomes. A long-term goal is to identify all the components of the endosomal/lysosomal apparatus using 2D electrophoresis and tandem mass spectroscopy. Therapy for Diseases that Affect the CNS. Effective gene therapy strategies for the treatment of human disease still remain highly experimental due to difficulties encountered in the actual application of many gene therapy schemes. Thus, we are developing novel approaches to address these limitations. Our strategies focus on "Bypass Therapy" an approach aiming at stimulating alternate pathways to bypass a cellular block caused by a specific gene defect.