David Libich, Ph.D.

Research

All cellular functions, activities, and communications are mediated by protein interactions. Despite their crucial importance, we know relatively little about many of these interactions due in large part to experimental limitations of structural biology. The central theme of the Libich Lab revolves around the determination of the structure and elucidation of the molecular mechanisms of highly dynamic and transient protein interactions. In conjunction with conventional biophysical approaches, we employ a host of cutting-edge NMR methods designed to detect and quantify kinetic, dynamic and structural information from such systems. Our current efforts are focused on understanding the assembly and functional interactions of low-complexity RNA-binding proteins involved in cancer and neurodegenerative processes. These types of proteins are challenging targets for biophysical characterization due to their extreme structural heterogeneity and propensity to aggregate. In particular, we are interested in the oncogenic fusion protein EWS-Fli1 and the structural implications of its role as the sole driver of Ewing's sarcoma. By characterizing, at atomic resolution, the structural features that contribute to both EWS-Fli1 self-association and its macromolecular interactions we will seek to understand the molecular basis of how it influences the genetic program of the cell. In a wider context, these studies will teach us more about the fundamental mechanisms of protein interactions, in both healthy and disease states.   Related Diseases: pediatric cancer, Ewing's sarcoma, synovial sarcoma, neurodegenerative processes, ALS, mitochondrial dysfunction, apoptosis, chaperones, protein folding, intrinsic disorder, intrinsically disordered proteins, cancer biology   Techniques: nuclear magnetic resonance (NMR), fluorescence spectroscopy, circular dichroic spectroscopy, analytical ultracentrifugation, light scattering, protein purification, site-directed mutagenesis, molecular cloning, biophysical and biochemical approaches