Our Science – Hall Website
Matthew D. Hall, Ph.D.
Matt was awarded a one-year Sir Keith Murdoch American-Australian Fellowship, which he spent with Prof. Val Culotta at the Johns Hopkins University Bloomberg School of Public Health. He then moved to Dr. Michael Gottesman's lab at the National Cancer Institute. There, he studies aspects of ABC drug transporters.
I have a diverse range of research interests at the NCI which have led to several intramural collaborations that aim to wed diverse discipline sets to tackle challenges in cancer chemotherapy.
Collateral sensitivity of MDR cells
This project has focused on the identification and development of compounds that are selectively toxic towards MDR cancer cells. This project brings together a number of approaches, including the elucidation of the compound’s mechanism of action and pre-clinical assessment of activity and validation of the molecular target in mouse tumors. A drug development program has identified agents with improved selective activity, and the mechanism of action of one such agent, tiopronin, is the current focus of investigation. I have also established a high-throughput screen to identify agents among the facility’s library of over 400,000 small molecules. This project will provide the most comprehensive database to date of drug transporter interactions, and I was recently awarded a competitive NIH R03 grant to conduct this screen.
Active work also continues on this important platinum class of drugs. We designed a whole-genome siRNA screen to identify genes associated with cisplatin resistance, and approval was received for this proposal. The initial screen has been performed and follow-up is currently underway. Several new genes associated with cisplatin resistance/sensitivity were identified, and follow-up will include testing the same siRNAs in sensitive cells and in the presence of the Pt drugs carboplatin and oxaliplatin. These experiments should give wide-ranging insight not only into sensitivity to the three Pt drugs used in the clinic, but also possible adjuvant therapies that might be developed.
Imaging transporter function at the blood-brain barrier
A collaboration with researchers in the National Institute of Mental Health (Innis and Pike) has helped to develop a radiolabeled P-glycoprotein substrate to be used for PET imaging of blood-brain barrier function. I am also investigating the possibility of using the P-gp radioligand substrate dLop an indicator of MDR in human tumors (the original aim of this project).
This page was last updated on 3/20/2013.