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James M. Phang, M.D.

James M. Phang, M.D.

  • Center for Cancer Research
  • National Cancer Institute
Mouse Cancer Genetics Program

RESEARCH SUMMARY

Dr. Phang’s laboratory, the Metabolism and Cancer Susceptiblity Section, pioneered studies of the regulatory functions of the amino acid, proline. His discoveries provided seminal insights into tumor reprogramming and metabolic epigenetics and introduced novel strategies for cancer therapy. Dr. Phang's laboratory showed that proline dehydrogenase (a.k.a. proline oxidase) is regulated by p53, PPARgamma and AMP-activated protein kinase (AMPK) to produce signaling reactive oxygen species (ROS) to initiate apoptosis, autophagy and other stress responses. Proline biosynthetic pathways regulate redox to control bioenergetics and cell growth. This metabolic axis constituted a new paradigm for epigenetics and for the regulation of stem cell development.

Areas of Expertise

1) tumor metabolism 2) metabolic reprogramming 3) epigenetics

Publications

Selected Key Publications

Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate

Hancock CN. Liu W, Alvord WG, Phang JM
Amino Acids. 2015. [ Journal Article ]

Proline biosynthesis augments tumor cell growth and aerobic glycolysis: involvement of pyridine Nucleotides.

Liu W, Hancock CN, Fischer JW, Harman M, Phang JM
Sci Rep. 5:17206. Doi: 10.1038/srep17206 [Journal Article]: 2015. [ Journal Article ]

Bridging epigenetics and metabolism: Role of non-essential amino acids

Phang JM, Liu W, Hancock C.
Epigenetics. 8: 231-6, 2013. [ Journal Article ]

Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC

Liu W, Le A, Hancock C, Lane AN, Dang CV, Fan TW, Phang JM.
Proc Natl Acad Sci U S A. 109: 8983-8, 2012. [ Journal Article ]

Proline oxidase functions as a mitochondrial tumor suppressor in human cancers

Liu Y, Borchert GL, Donald SP, Diwan BA, Anver M, Phang JM
Cancer Res. 69: 6414-22, 2009. [ Journal Article ]