Vincent S. Tagliabracci
Expanding the Human Kinome
Protein kinases are an important class of enzymes that transfer phosphate from ATP to protein substrates, a process known as phosphorylation. These "chemical tags" can drastically alter the function of a protein. Virtually every cellular process is regulated by protein kinases, and abnormal phosphorylation has been linked to numerous diseases such as cancer, neurodegeneration and diabetes. In fact, protein kinases are so important that drugs targeting them can sometimes cure these deadly diseases. More than 500 human protein kinases have been identified and assembled into an evolutionary tree known as the human "kinome". However, research is largely biased toward kinases with well-established roles in disease; it has been estimated that the molecular functions of more than 50% of human kinases remain uncharacterized. Furthermore, several new kinase families have been identified that are so different, they were not even included on the human kinome tree.
Our lab uses a combination of bioinformatics, biochemistry and structural biology to uncover novel, atypical, and uncharacterized protein kinase families that escaped identification by more traditional approaches. This strategy has expanded the human kinome and shed light on human diseases such as cancer and bone disorders. We discovered the Fam20-family of secreted kinases, which solved a 130-year-old mystery of how secreted proteins, such as casein, become phosphorylated. More recently, we have uncovered kinases that have novel enzymatic activities. These results have opened up new areas of research on how our cells cope with oxidative stress and how bacterial pathogens evade our immune system. We anticipate that our work has potential to define new paradigms in cellular regulation and signal transduction, which could translate into innovative diagnostic tools and treatments for human diseases.