The SakmarLab uses genetic, biochemical and biophysical methods to learn how signals from outside a cell are relayed across its membrane and into the cell interior, where they elicit responses via the process of signal transduction. Much of our work focuses on molecules known as G protein coupled receptors (GPCRs), or seven-transmembrane heptahelical receptors, which are key to a wide range of signal transduction pathways.

 

The primary research focus of the SakmarLab is to study the biology and chemistry of heptahelical GPCRs. For the past five years, members of the SakmarLab have been working to develop or adapt various innovative methods to establish a robust interdisciplinary approach to support the following long-term goals:

 

  • To elucidate the basic principles that underlie ligand recognition and specificity in heptahelical receptors,

     

  • To understand the molecule mechanism of receptor activation and signaling, including the details of dynamic conformational changes required to switch a receptor from its “off” state to its “on” state,

     

  • To understand how specific receptor proteomics and post-translational modifications such as glycosylation, acylation, phosphorylation and tyrosine sulfation, affect receptor function,

     

  • To elucidate how receptors assemble in biological membrane bilayers and how the physical and chemical properties of the membrane affect receptor biology,

     

  • To establish a basic foundation for drug discovery aimed at modulating the pharmacological activity of heptahelical receptors responsible for disease states.

 

The SakmarLab focuses primarily on Class A (rhodopsin family) GPCRs; namely visual pigments and chemokine receptors, but other receptors and other aspects of G protein-mediated signaling are also under investigation.