Ronald C. Rubenstein, MD, PhD

Washington University in St. Louis (WU)

My primary research focus has been on basic (laboratory) and translational (clinical) studies of novel means to correct the dysfunction of mutant CFTR proteins. Our data that sodium 4-phenylbutyrate (4PBA) improved the intracellular trafficking and function of the most common CFTR mutation in CF, F508del, and our pilot clinical trial of 4PBA that demonstrated small improvements in F508del function in people with CFl were a crucial proof of concept that have supported larger efforts that have resulted in now approved drugs for CF. Our investigations into the mechanism(s) underlying this effect have focused on how 4PBA-regulated molecular chaperones modulate the trafficking of CFTR and other relevant proteins in epithelial cells and other model systems. We also have mechanistic and translational interest in Cystic Fibrosis Related Diabetes and in hearing loss due to aminoglycoside therapy in people with CF; these emerging clinical problems negatively impact outcomes and quality of life.