University of Kentucky
Associate Director, Center for Structural Biology.
Professor of Molecular and Cellular Biochemistry.
Director, REU Summer Program in Biochemistry, Department of Molecular and Cellular Biochemistry.
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine.
Department of Biochemistry and Molecular Biophysics, Washington University at St. Louis.
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill.
Department of Biochemistry and Molecular Biology, The Milton S. Hershey Medical Center, The Pennsylvania State University.
Ph.D. (Physical Chemistry), University of Western Australia.
B.Sc. with 1st Class Honours (Physical and Inorganic Chemistry), University of Western Australia.
After many years of working on protein folding and related issues, the Creamer lab is now applying its expertise to the characterization of the function and conformational properties of intrinsically disordered regions (IDRs) within proteins. IDRs are regions of protein sequence that do not appear to adopt a well-defined structure. Many of these appear to gain structure (i.e. fold) when bound by another biomolecule. The folding transition that occurs upon this binding can be important for the function of the protein.
We have chosen calmodulin (CaM) and its targets as model systems to study folding transitions within IDRs. CaM is a vital calcium sensor protein that is highly-conserved from yeast to man and is a regulator of many important enzymes. It was recently proposed that the sequences that CaM binds are often IDRs. Our current studies are focused on calcineurin (CaN), a Ser/Thr phosphotase that is activated by CaM binding. CaN plays essential roles in memory development and retention, cardiac growth, and immune system activation. It has been implicated in numerous disorders including Down syndrome, cardiac hypertrophy, and autoimmune disorders. The regulatory domain of CaN, which is a CaM substrate, is an IDR. We are investigating the CaM-CaN interaction and how this regulates CaN function.
We are planning to extend this work to include other regulators of CaN including Rcan1, a protein that plays a role in Down syndrome, and CHP1. We are also exploring folding transitions in other CaM substrates.