Professor, Cellular and Molecular Medicine
Professor, Applied BioSciences - GIDP
Professor, Cancer Biology - GIDP
Professor, Genetics - GIDP
Dr. Fares is a Professor of Molecular and Cellular Biology and a member of the University of Arizona Cancer Center. The goal of his studies is to decipher a novel cell biological pathway linking regulators of endosomal and lysosomal transport; this will advance the field of membrane transport, identify the basis for tissue-specific death in some diseases, and identify potential therapies for the lysosomal storage disorder Mucolipidosis type IV.
Dr. Fares established the C. elegans model of this disease ten years ago and his group has made significant contributions in using it to elucidate functions of the Mucolipidosis type IV protein (TRPML1/mucolipin-1 in mammals and CUP-5 in C. elegans) and to understand the basis of the Mucolipidosis type IV lysosomal dysfunction and tissue degeneration.
Furthermore, he has significant experience in genetic and cell biological analyses of membrane trafficking in C. elegans. In summary, he has a demonstrated record of productive research projects in Mucolipidosis type IV and membrane trafficking.
Lysosomes are membrane-bound organelles that serve as the major degradative compartments for endocytic, phagocytic, and autophagic materials targeted for destruction in eukaryotic cells. Lysosomes also mediate some cell death pathways and play crucial roles in wound repair. Indeed, lysosomal dysfunction is a hallmark of many diseases, including some referred to as lysosomal storage disorders. Given this central importance of lysosomes, it is striking that little is known about how lysosomes are formed, the process we refer to as lysosome biogenesis.
Mucolipidosis type IV is a neurodegenerative lysosomal storage disorder that is characterized by severe psychomotor retardation, achlorhydria, and ophthalmological abnormalities; most tissues show lysosomal defects resulting in abnormally enlarged vacuoles that accumulate various material. In spite of this general lysosomal defect, neurons are the primary cells that die in Mucolipidosis type IV patients. Mucolipidosis type IV is due to mutations in the gene MCOLN1 that encodes the transient receptor potential protein TRPML1/mucolipin-1. It is still not known how loss of TRPML1 leads to lysosomal defects and neuronal death.
The goals of our studies are two-fold:
- To elucidate mechanisms of lysosome biogenesis.
- To decipher the basis for lysosomal dysfunction and cell death in the lysosomal storage disorder Mucolipidosis type IV.