Biophysical and crystallographic studies of cellular adhesion and receptor signaling

My lab is interested in mechanistic studies of cellular adhesion and receptor-mediated signaling. The biological processes in which we are interested include adhesion of platelets to collagen, formation of biofilms by Staphylococcus epidermidis, and activation of immune responses by IgA and IgG antibodies. 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, isothermal titration calorimetry, and surface plasmon resonance 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, 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. Biofilms are bacterial communities encased in a polysaccharide slime that are resistant to antibiotic treatment and host immune response; specifically, S. epidermidis biofilms are responsible for recurrent infections after surgery. Finally, development of antibodies capable of inducing more potent immune responses could lead to more effective anti-cancer therapies. Support for trainees is available from Training Grants in Cardiovascular Research and Biologic Threat Agents.

Herr Lab Site

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