Matthew D. Hall, Ph.D.
Staff Scientist

Center for Cancer Research
National Cancer Institute

Building 37, Room 2112
Bethesda, MD 20892
301-496-1104

Matt Hall earned a BSc (Hons I) and PhD in Chemistry at the University of Sydney, under Professor Trevor Hambley. His thesis developed synchrotron spectroscopic techniques to monitor the cellular distribution and metabolism of the cancer drug cisplatin, and other Pt-based complexes. For this work, Matt was awarded the ASRP medal, and an Australian Academy of Sciences fellowship. 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.

Areas of Expertise
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? 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? 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.

Cisplatin resistance 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).

Selected Publications
  1. Pluchino KM, Hall MD, Goldsborough AS, Callaghan R, Gottesman MM.
    Drug Resist. Updat.. 15: 98-105, 2012. [ Journal Article ]
  2. Hall MD, Daly HL, Zhang JZ, Zhang M, Alderden RA, Pursche D, Foran GJ, Hambley TW.
    Metallomics. 4: 568-75, 2012. [ Journal Article ]
  3. Pouliot LM, Shen DW, Suzuki T, Hall MD, Gottesman MM.
    Exp. Cell Res.. 319: 566-74, 2013. [ Journal Article ]
  4. Shen DW, Pouliot LM, Hall MD, Gottesman MM.
    Pharmacol. Rev.. 64: 706-21, 2012. [ Journal Article ]
  5. Pouliot LM, Chen YC, Bai J, Guha R, Martin SE, Gottesman MM, Hall MD.
    Cancer Res.. 72: 5945-55, 2012. [ Journal Article ]

Matt Hall earned a BSc (Hons I) and PhD in Chemistry at the University of Sydney, under Professor Trevor Hambley. His thesis developed synchrotron spectroscopic techniques to monitor the cellular distribution and metabolism of the cancer drug cisplatin, and other Pt-based complexes. For this work, Matt was awarded the ASRP medal, and an Australian Academy of Sciences fellowship. 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.

Summary

Matt Hall earned a BSc (Hons I) and PhD in Chemistry at the University of Sydney, under Professor Trevor Hambley. His thesis developed synchrotron spectroscopic techniques to monitor the cellular distribution and metabolism of the cancer drug cisplatin, and other Pt-based complexes. For this work, Matt was awarded the ASRP medal, and an Australian Academy of Sciences fellowship. 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.

Areas of Expertise
drug transporters

Research

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? 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? 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.

Cisplatin resistance 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).

Publications

Selected Publications
  1. Pluchino KM, Hall MD, Goldsborough AS, Callaghan R, Gottesman MM.
    Drug Resist. Updat.. 15: 98-105, 2012. [ Journal Article ]
  2. Hall MD, Daly HL, Zhang JZ, Zhang M, Alderden RA, Pursche D, Foran GJ, Hambley TW.
    Metallomics. 4: 568-75, 2012. [ Journal Article ]
  3. Pouliot LM, Shen DW, Suzuki T, Hall MD, Gottesman MM.
    Exp. Cell Res.. 319: 566-74, 2013. [ Journal Article ]
  4. Shen DW, Pouliot LM, Hall MD, Gottesman MM.
    Pharmacol. Rev.. 64: 706-21, 2012. [ Journal Article ]
  5. Pouliot LM, Chen YC, Bai J, Guha R, Martin SE, Gottesman MM, Hall MD.
    Cancer Res.. 72: 5945-55, 2012. [ Journal Article ]

Biography

Matt Hall earned a BSc (Hons I) and PhD in Chemistry at the University of Sydney, under Professor Trevor Hambley. His thesis developed synchrotron spectroscopic techniques to monitor the cellular distribution and metabolism of the cancer drug cisplatin, and other Pt-based complexes. For this work, Matt was awarded the ASRP medal, and an Australian Academy of Sciences fellowship. 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.