Protein Processing
Modification of proteins with a conserved polypeptide called ubiquitin regulates many aspects of cell biology and is involved in the pathogenesis of many diseases. This modification process is known as ubiquitination and is catalyzed by three enzymes, one of which is a family of enzymes called ubiquitin ligase.  There are hundreds of predicted ubiquitin ligases in the DNA database.  However, to date, the majority of the ubiquitin ligases have not been investigated. 

 My lab focuses on the endoplasmic reticulum-resident ubiquitin ligase gp78 and its related proteins. We want to understand how gp78-catalyzed ubiquitination eliminates unwanted proteins from the endoplasmic reticulum and protects the vital function of the secretory pathway. We also investigate how gp78 acts in disease, for example, cancer and neurodegenerative diseases - particularly Huntington’s disease. Another focus of my lab is to understand how failure to remove unwanted proteins from the endoplasmic reticulum contributes to development and progression of cystic fibrosis, a-1-antitrypsin deficiency, cancer, or many neurodegenerative diseases. Lastly, we are also interested in ubiquitin ligase-targeted drug discovery. Towards this effort, we are establishing an assay for high throughput screening for compound modulators of disease-causing ubiquitin ligases and ligases essential for regulation of specific cellular process, for example, regulation of human embryonic stem cell differentiation.