Richard Kriwacki

Richard Kriwacki was amongst the first to show that intrinsically disordered proteins (IDPs) perform important biological functions in cells. After earning a Ph.D. degree in chemistry/biophysics at Yale University, he took up structural studies of the p53 tumor suppressor pathway at the Scripps Research Institute in La Jolla, CA. Here, he discovered that the p53-regulated protein, p21, is disordered prior to binding and inhibiting the entire family of cyclin-dependent kinases (Cdks) that regulate cell division. In 1997, Richard joined the Department of Structural Biology at St. Jude Children’s Research Hospital, where he used NMR spectroscopy and other biophysical methods, and biochemical and cellular assays, to study the roles of IDPs in key cellular processes often altered in cancer, including cell division, apoptosis, and ribosome biogenesis. The findings revealed mechanistic synergies between folded domains and disordered regions of proteins that mediate diverse biological functions. In 2014, he and co-workers discovered that Nucleophosmin (NPM1), a highly abundant phospho-protein, undergoes phase separation with nascent ribosomal components in the nucleolus and are now investigating the role of phase separation in ribosome assembly.

Given that disordered proteins are often associated with human disease, Richard has applied NMR and other methods to test the idea that small molecules can be developed to bind and alter the function of disordered proteins. Because many disease-associated IDPs also undergo phase separation, Richard is now pursuing strategies to leverage small molecules to alter aberrant phase separation in cells and reverse disease phenotypes.

Richard has been a long-standing advocate for recognition of the roles of IDPs in biology and disease, having co-founded the Intrinsically Disordered Proteins Subgroup of the Biophysical Society, and co-organized/co-chaired numerous meetings on IDPs, including the Gordon Research Conference, a Biophysical Society Thematic meeting, and several Telluride Science Research Center workshops.