Our laboratory is interested in mechanistic studies of cellular adhesion and receptor-mediated signaling in immunology and microbiology. The biological processes we are interested in include formation of biofilms by Staphylococcus aureus and S. epidermidis, activation of immune responses by IgA and IgG antibodies, and adhesion of platelets to collagen. Each of these processes is dependent upon specific interactions between proteins on different cells, or between soluble proteins and cell-surface receptors.
We are interested in understanding the specific details of these macromolecular interactions, both in terms of the atomic structures of the proteins involved and the thermodynamics of binding. To study these interactions, we use protein x-ray crystallography to gain structural insight and various biophysical techniques such as analytical ultracentrifugation, surface plasmon resonance, circular dichroism spectroscopy, or isothermal titration calorimetry to study the binding interactions and stoichiometries of protein-protein complexes. Understanding these processes at the molecular level will be crucial for the development of novel therapies. For example, biofilms are bacterial communities encased in a polysaccharide slime that are resistant to antibiotic treatment and host immune response.
Our lab discovered novel approaches to inhibit biofilm formation that are being developed as a therapeutic approach. Although IgA and IgG antibodies are critical for host immune responses to infection, formation of antibody immune complexes can lead to pathology in many autoimmune diseases. Finally, platelet adhesion to collagen is the first step in thrombus formation, normally responsible for limiting blood loss but potentially leading to heart attack and stroke.