Research Interests

Primary focus of our lab is to investigate cellular machinery that mediate protein homeostasis—with a particular emphasis on the ubiquitin-proteasome system—and how it relates to major human diseases like cancer. Three questions motivate our research: (1) How do cells maintain protein homeostasis (2) How do changes in protein homeostasis lead to disease pathogenesis and (3) Can intervening protein homeostasis be used to treat diseases

The proteome is constantly remodelled to meet the changing environmental challenges of the cell. Protein degradation facilitated by the ubiquitin-proteasome system (UPS) is a major contributor to proteome remodelling. In this pathway, ubiquitin is activated and transferred to substrates via an E1-E2-E3 enzymatic cascade. A wide cross-section of the proteome is subject to ubiquitination at some point during its lifetime. It is a posttranslational modification that maintains a normal cellular repertoire of functional proteins. UPS is majorly involved in the degradation of regulatory proteins that control crucial cellular processes such as cell cycle control proteins, transcription factors and checkpoint control proteins. It has become increasingly clear over the past decade that protein ubiquitination is critical to the health of cells and organisms. Gaining a deeper understanding of protein ubiquitination and degradation may shed light on how diseases develop, which in turn may lead to new methods of diagnosis and therapy.

As such, there are two central challenges facing the field. First, a complete description of the ubiquitinome—the array of proteins that are modified by the ubiquitin system and second central challenge for the field is matching ubiquitylation targets with the vast array of ubiquitylation machinery encoded by eukaryotic genomes. Our recent research has focused on identification of substrates of important E3 ubiquitin ligases such as E6AP, Fbw7α, Skp2, Itch, TRAF and others which are involved in pathogenesis of myeloid leukaemia and breast cancer. With the expertise in proteomics, biochemistry and collaboration with number of groups our goal is to develop a molecular understanding that will aid development of better diagnostic marker or therapeutic compound for life threatening disease.