James B. McMahon, Ph.D.
James B. McMahon, Ph.D.
Chief
Senior Investigator
Head, Assay Development and Screening Section

Dr. McMahon has been instrumental in the development of in vitro model systems for the discovery of new bioactive molecules from natural products. Beginning with the development and characterization of human tumor cell lines used in the NCI60 cell line panel, Dr. McMahon went on to establish CCR’s Molecular Targets Laboratory (MTL). The MTL leverages CCR basic science discoveries into bioassays and high throughput screens. His expertise in assay development and high throughput screening has enabled the MTL to discover novel natural products that modulate distinct molecular targets in cancer and AIDS.

Areas of Expertise
1) assay development, 2) high throughput screening, 3) mechanism of action, 4) in vitro model systems, 5) microscopy, 6) molecular pharmacology

Contact Info

James B. McMahon, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 560, Room 11-68
Frederick, MD 27102-1201
301-846-5391
mcmahoja@mail.nih.gov

The development and validation of cell-based assays for the discovery of potent reagents which selectively target cancer cells have been long-term goals of our Program. Since the early 1980's, continuing advances in cell culture techniques have allowed for remarkable breakthroughs in cancer cell biology. Early in vitro studies involving neoplastic transformation of rodent cells have provided valuable insights into the carcinogenic process. The ability to propagate both normal and malignant cells from a variety of experimental animal species set the stage for the necessary refinements of technologies to allow for the maintenance of human cells and tissues in vitro.

Our laboratory has been at the forefront of the establishment and characterization of human tumor cell lines and their normal cell counterparts for use in bioassays. With the establishment of the NCI 60-cell panel and the creation of the Compare analysis program, many new classes of anticancer compounds were discovered. As was the case with many of the early cell-based screens, designed to screen for cytotoxic agents, most of the compounds were of limited clinical potential. The new era of genomics and proteomics along with advances in automation technologies are now providing insights into the molecular pathogenesis of cancer. These technologies will provide unprecedented opportunities for discovery and development of novel, molecularly-targeted agents for cancer. Our primary goal is to use this ever-increasing knowledge base to develop and characterize novel cell bioassays which will target specific molecular targets and/or pathways. New in vitro assay formats and endpoints will be utilized to serve as platforms for examining the effects of test compounds on cells engineered with reporters linked to specific molecular targets.

It is hoped that establishment of cellular assays based on this approach will quickly lead to the discovery of new, effective anticancer compounds with unique mechanism of action. Though the main emphasis of research in the MTDP is aimed toward reducing the human cost of cancer, the program proactively interacts with collaborators to address other health-related concerns of high priority to the DHHS. One example of this type of interaction is the current collaboration between the MTDP and USAMRIID to test antiviral compounds, previously discovered in the MTDP, against a variety of emerging threats including the ebola virus and the virus responsible for sudden acute respiratory syndrome (SARS). In addition, MTDP's previous discoveries of potent anti-viral natural product peptides has resulted in the establishment of a worldwide network of collaborators who are employing the peptides for the microbiocidal protection from HIV. Through the responsible development of such collaborations, the MTDP extends the products of its screening and isolation efforts into areas of significant national and international need.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Chemical Biology, Molecular Biology and Biochemistry
Selected Key Publications
  1. Woldemichael GM, Vasselli JR, Gardella RS, McKee TC, Linehan WM, McMahon JB.
    J Biomol Screen. 11(6): 678-87, 2006. [ Journal Article ]
  2. Henrich CJ, Robey RW, Bokesch HR, Bates SE, Shukla S, Ambudkar SV, Dean M, McMahon JB.
    Mol. Cancer Ther. 6(12): 3271-8, 2007. [ Journal Article ]
  3. Kang MI, Henrich CJ, Bokesch HR, Gustafson KR, McMahon JB, Baker AR, Young MR, Colburn NH.
    Mol. Cancer Ther. 8(3): 571-81, 2009. [ Journal Article ]
  4. Woldemichael GM, Turbyville TJ, Linehan WM, McMahon JB.
    Cancer Res. 71(1): 134-42, 2011. [ Journal Article ]
  5. Woldemichael GM, Turbyville TJ, Vasselli JR, Linehan WM, McMahon JB.
    Neoplasia. 14(8): 771-7, 2012. [ Journal Article ]

Dr. McMahon received his Ph.D. in cell biology from the University of Vermont, and in 1978 he joined the NCI's Chemical Carcinogenesis Program. In 1983, Dr. McMahon joined the Laboratory of Experimental Therapeutics and Metabolism within the NCI's Developmental Therapeutics Program (DTP). In 1988, he was tenured to senior investigator and served in the DTP's Program Development Research Group. Dr. McMahon joined the Laboratory of Drug Discovery Research and Development, DTP, at its inception in 1990. Dr. McMahon currently is the Director of the CCR's Molecular Targets Development Program. He is extensively involved in cell-based screening assay development and applications for anti-HIV and anti-tumor lead discovery from natural products. Dr. McMahon has published widely and has been awarded over thirty patents. In addition, he is a member of both the Molecular Targets Faculty and the Molecular Targets Steering Committee.

Name Position
Emad Darvishi Postdoctoral Fellow (Visiting)
Curtis J. Henrich, Ph.D. Staff Scientist (Contr)
Tanya Ransom M.S. Research Biologist
Emily Smith M.S. Research Assistant (Contr)
Antony Wamiru B.S. Laboratory Technician (Contr)
Jennifer Wilson A.S. Biological Laboratory Technician
Girma M. Woldemichael, Ph.D. Staff Scientist (Contr)

Research

The development and validation of cell-based assays for the discovery of potent reagents which selectively target cancer cells have been long-term goals of our Program. Since the early 1980's, continuing advances in cell culture techniques have allowed for remarkable breakthroughs in cancer cell biology. Early in vitro studies involving neoplastic transformation of rodent cells have provided valuable insights into the carcinogenic process. The ability to propagate both normal and malignant cells from a variety of experimental animal species set the stage for the necessary refinements of technologies to allow for the maintenance of human cells and tissues in vitro.

Our laboratory has been at the forefront of the establishment and characterization of human tumor cell lines and their normal cell counterparts for use in bioassays. With the establishment of the NCI 60-cell panel and the creation of the Compare analysis program, many new classes of anticancer compounds were discovered. As was the case with many of the early cell-based screens, designed to screen for cytotoxic agents, most of the compounds were of limited clinical potential. The new era of genomics and proteomics along with advances in automation technologies are now providing insights into the molecular pathogenesis of cancer. These technologies will provide unprecedented opportunities for discovery and development of novel, molecularly-targeted agents for cancer. Our primary goal is to use this ever-increasing knowledge base to develop and characterize novel cell bioassays which will target specific molecular targets and/or pathways. New in vitro assay formats and endpoints will be utilized to serve as platforms for examining the effects of test compounds on cells engineered with reporters linked to specific molecular targets.

It is hoped that establishment of cellular assays based on this approach will quickly lead to the discovery of new, effective anticancer compounds with unique mechanism of action. Though the main emphasis of research in the MTDP is aimed toward reducing the human cost of cancer, the program proactively interacts with collaborators to address other health-related concerns of high priority to the DHHS. One example of this type of interaction is the current collaboration between the MTDP and USAMRIID to test antiviral compounds, previously discovered in the MTDP, against a variety of emerging threats including the ebola virus and the virus responsible for sudden acute respiratory syndrome (SARS). In addition, MTDP's previous discoveries of potent anti-viral natural product peptides has resulted in the establishment of a worldwide network of collaborators who are employing the peptides for the microbiocidal protection from HIV. Through the responsible development of such collaborations, the MTDP extends the products of its screening and isolation efforts into areas of significant national and international need.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Chemical Biology, Molecular Biology and Biochemistry

Publications

Selected Key Publications
  1. Woldemichael GM, Vasselli JR, Gardella RS, McKee TC, Linehan WM, McMahon JB.
    J Biomol Screen. 11(6): 678-87, 2006. [ Journal Article ]
  2. Henrich CJ, Robey RW, Bokesch HR, Bates SE, Shukla S, Ambudkar SV, Dean M, McMahon JB.
    Mol. Cancer Ther. 6(12): 3271-8, 2007. [ Journal Article ]
  3. Kang MI, Henrich CJ, Bokesch HR, Gustafson KR, McMahon JB, Baker AR, Young MR, Colburn NH.
    Mol. Cancer Ther. 8(3): 571-81, 2009. [ Journal Article ]
  4. Woldemichael GM, Turbyville TJ, Linehan WM, McMahon JB.
    Cancer Res. 71(1): 134-42, 2011. [ Journal Article ]
  5. Woldemichael GM, Turbyville TJ, Vasselli JR, Linehan WM, McMahon JB.
    Neoplasia. 14(8): 771-7, 2012. [ Journal Article ]

Biography

Dr. McMahon received his Ph.D. in cell biology from the University of Vermont, and in 1978 he joined the NCI's Chemical Carcinogenesis Program. In 1983, Dr. McMahon joined the Laboratory of Experimental Therapeutics and Metabolism within the NCI's Developmental Therapeutics Program (DTP). In 1988, he was tenured to senior investigator and served in the DTP's Program Development Research Group. Dr. McMahon joined the Laboratory of Drug Discovery Research and Development, DTP, at its inception in 1990. Dr. McMahon currently is the Director of the CCR's Molecular Targets Development Program. He is extensively involved in cell-based screening assay development and applications for anti-HIV and anti-tumor lead discovery from natural products. Dr. McMahon has published widely and has been awarded over thirty patents. In addition, he is a member of both the Molecular Targets Faculty and the Molecular Targets Steering Committee.

Team

Name Position
Emad Darvishi Postdoctoral Fellow (Visiting)
Curtis J. Henrich, Ph.D. Staff Scientist (Contr)
Tanya Ransom M.S. Research Biologist
Emily Smith M.S. Research Assistant (Contr)
Antony Wamiru B.S. Laboratory Technician (Contr)
Jennifer Wilson A.S. Biological Laboratory Technician
Girma M. Woldemichael, Ph.D. Staff Scientist (Contr)