Steve Gamblin uses a combination of structural, biophysical and functional studies to understand molecules involved in diseases such as influenza, diabetes and cancer. Work on influenza is focused on the two major surface glycoproteins of the virus, hemagglutinin (HA) and neuraminidase (NA). This work has addressed the mechanistic basis of the receptor specificity of HA – an important issue in the transmission of viruses from birds and swine to humans and thus the occurrence of a pandemic. Work on NA has described the mechanism for influenza viruses acquiring resistance to anti-viral drugs like Tamiflu.
Work relevant to diabetes has focused on understanding the structural and mechanistic basis of energy sensing and regulation by the human AMP-dependent Protein Kinase (AMPK). This enzyme is the target for the most commonly used drugs to treat type 2 diabetes and understanding its structure/mechanism is aiding novel drug design.
Gamblin’s laboratory has a long-term interest in how covalent modifications of histones, the molecules that package DNA into chromatin, regulate gene expression through epigenetic mechansims. Work in this area has established the structural/functional basis of histone methylation by SET domains and shown novel mechanisms for the regulation of this activity in the context of the Polycomb Repressive Complex 2 (PRC2). These studies have provided important insights into the propagation of repressive chromatin domains, and it is hoped they will lead to the identification of small molecule inhibitors that may be of use in certain cancers.