For the CFTR biogenesis, current evidence suggests that Endoplasmic Reticulum (ER) membrane protein complex (EMC) is important for CFTR synthesis and function. EMC is a well conserved protein complex consisting of multi-subunits. Mouse model with deficiency of EMC3, a core subunit of EMC, is utilized to study the in vivo role of EMC in CFTR.
For CFTR degradation, the focus is on the ER-associated degradation (ERAD) pathway, particularly on factors within the ER lumen. ERAD is a critical QC pathway at the ER, ensuring the misfolded newly synthesized proteins to be degraded by proteasome. The interactions between CFTR and ER luminal DNAJB family members are under investigation using in vitro and in vivo models.
CFTR modulators, which are small molecules targeting CFTR, have been approved by the FDA to treat patients with CF with some common CFTR mutations, and have greatly improved the patient’s life quality. However, patients with many rare CFTR mutations are not eligible for this therapy. CF theragnostic program is using nasal cells from patients and testing in vitro the efficacy of current CFTR modulators on CFTR mutants present in these patients.
The goal of Dr. Huang’s research above is to identify the targets that would potentially improve the surface functional expression of mutant CFTR in patients.