It is well established that cancer cells reprogram their metabolism to meet the biosynthetic challenge of growth and proliferation. How cancer metabolism is initiated and maintained in cancer cells is a central question of cancer research. We have pioneered the novel concept that histone lysine methyltransferases and demethylases are key players in reprogramming cell metabolism for cancer cell growth and proliferation. Therefore, they represent a new class of metabolic oncogenes or tumor suppressors and new drug targets for cancer therapy. We were the first to provide experimental evidence in support of this model by showing that the histone H3 lysine 9 methyltransferase G9A and demethylase KDM4C epigenetically activate amino acid biosynthesis and transport to sustain cancer cell survival and proliferation.
We are currently investigating how oncogenic transcription factors, such as MYCN and ATF4, cooperate with epigenetic regulators, such as enzymes that modify histones and RNA, in transcriptional and translational reprogramming of cancer metabolism. We study metabolic pathways that generate building blocks for the synthesis of proteins, lipids, and nucleotides. We are also testing small molecule inhibitors and drugs that block key metabolic pathways as cancer therapeutics in cell lines and animal models of human cancer.
