Cancer Research Focus

Collateral Sensitivity of ABC Transporters-expressing Cancer Cells -  Our research objectives over the past several decades have focused on the role of ABC transporters as mediators of multi-drug resistance in cancer cells.  Higher levels of ABCB1, ABCC1 and ABCG2 has been demonstrated to confer multi-drug resistance through energy-dependent efflux of anti-cancer drugs.

Paradoxically, ABC transporters also confer hypersensitivity (or Collateral Sensitivity) to specific drugs onto the same drug resistant cells. Understanding the molecular mechanism of ABC transporters-mediated Collateral Sensitivity should allow the development of novel treatment strategy that could prevent the rise of chemo-resistant cancers in patients…. MORE

Regulation of ABC Transporters Functions Through Proteins Interactions -   ABC proteins mediate the transport of several normal physiological ligands (e.g., heme, sterols, lipids, uric acid, LTC4, glutathione, cGMP, etc.), in addition to their protective functions at the blood brain barrier and fetal placenta membranes. Moreover, mutations in these proteins have been shown to cause several human genetic diseases (e.g., cystic fibrosis, hepatic disorder, hyperuricemia and gout disease). Moreover, the over-expression of several ABC proteins (e.g., ABCB1, ABCG2 and ABCC1) in tumour cells pre- or post-chemotherapeutic treatment of clinical samples have been linked to treatment failure of cancer patients. 

Given the functions of ABC transporters in normal and disease manifestations, it remains unclear how these proteins are regulated. Few ABC interacting proteins have been identified and their regulatory effects determined.  Hence, filling this significant void in our understanding of ABC protein regulations will advance our understanding of this major family of evolutionary conserved proteins.

Our research objectives are to map the human ABC interactome, beginning with the best biochemically characterized ones (e.g., ABCB1, G2 and C1) and determine how such interacting proteins regulate their ligand transport functions…. MORE