HOW CAN WE HELP YOU? Call 1-800-TRY-CHOP
The Rubenstein Lab focuses on basic and translational studies of the mechanisms underlying the pathophysiology of cystic fibrosis (CF), especially novel means to correct the dysfunction of mutant cystic fibrosis transmembrane conductance regulator (CFTR) proteins.
Initial in vitro work conducted in the lab demonstrated that a small molecule, sodium 4-phenylbutyrate (4PBA), improved the intracellular trafficking and function of the most common CFTR mutation, F508del. These data led to a pilot clinical trial of 4PBA that demonstrated small improvements in DF508 function in people with CF. These findings represented a crucial proof of concept that led to larger efforts to identify correctors of F508del trafficking and function that are now approved drugs.
Recently, investigations in the Rubenstein Lab have focused on how 4PBA-regulated molecular chaperones modulate the trafficking of CFTR in epithelial cells and model systems. Because relative hyperfunction of the epithelial sodium channel (ENaC) is also a characteristic feature of the CF airway, the team has increasingly focused on how these 4PBA-regulated chaperones influence ENaC trafficking, as well as how CFTR itself may modulate ENaC trafficking and function.
In particular, the lab is focused on one novel chaperone present in the lumen of the endoplasmic reticulum, ERp29, the first luminal chaperone demonstrated to positively regulate CFTR biogenesis. Through these studies, the lab has gained expertise in molecular and physiologic techniques, including Ussing chambers, to study epithelial ion channel trafficking and function as well as in the detection of CFTR and ENaC.
The Rubenstein Lab recently developed a keen mechanistic and translational interest in cystic fibrosis-related diabetes mellitus (CFRD), an emerging clinical problem that increases morbidity and mortality in people with CF. The underlying basis of CFRD is poorly understood, and the Rubenstein Lab is beginning to apply things learned from its previous work to these problems as well.
Ronald C. Rubenstein, MD, PhD
Director, Cystic Fibrosis Center
Dr. Rubenstein's research focuses on basic and translational studies of novel means to improve outcomes in cystic fibrosis. He initially focused on correcting the dysfunction of mutant cystic fibrosis transmembrane conductance regulator (CFTR) proteins, which led him to study how molecular chaperones regulate the biogenesis and trafficking of CFTR and other proteins that are relevant to cystic fibrosis.