Positions

Overview

  • Our group studies the molecular mechanisms that control the metabolic processes critical for sustaining cancer cell growth and proliferation, with a focus on the childhood cancer neuroblastoma. We investigate how cancer cells increase the production of building blocks for the synthesis of macromolecules for cell growth and proliferation, which may direct the development of new cancer therapeutics designed to target vulnerabilities of cancer cells.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2022 A Negative Regulatory Role for RKIP in Breast Cancer Immune Response.Cancers.  14. 2022
    2022 H3K9me3 represses G6PD expression to suppress the pentose phosphate pathway and ROS production to promote human mesothelioma growthOncogene.  41:2651-2662. 2022
    2022 Single-Nucleus Transcriptional Profiling of Chronic Kidney Disease after Cisplatin NephrotoxicityAmerican Journal of Pathology.  192:613-628. 2022
    2022 G6PD functions as a metabolic checkpoint to regulate granzyme B expression in tumor-specific cytotoxic T lymphocytesJournal for ImmunoTherapy of Cancer.  10. 2022
    2021 ATF3 promotes the serine synthesis pathway and tumor growth under dietary serine restrictionCell Reports.  36. 2021
    2021 Therapeutic targeting of both dihydroorotate dehydrogenase and nucleoside transport in MYCN-amplified neuroblastomaCell Death and Disease.  12. 2021
    2020 P53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney diseaseJournal of Clinical Investigation.  130:5011-5026. 2020
    2020 Competitive ubiquitination activates the tumor suppressor p53Cell Death and Differentiation.  27:1807-1818. 2020
    2020 PRMT1 promotes neuroblastoma cell survival through ATF5Oncogenesis.  9. 2020
    2020 ATF3 promotes erastin-induced ferroptosis by suppressing system XcCell Death and Differentiation.  27:662-675. 2020
    2019 Glycine decarboxylase is a transcriptional target of MYCN required for neuroblastoma cell proliferation and tumorigenicityOncogene.  38:7504-7520. 2019
    2019 Metabolic reprogramming by MYCN confers dependence on the serine-glycine-one-carbon biosynthetic pathwayCancer Research.  79:3837-3850. 2019
    2019 Bif-1 interacts with prohibitin-2 to regulate mitochondrial inner membrane during cell stress and apoptosisJournal of the American Society of Nephrology.  30:1174-1191. 2019
    2019 BMP4 and Neuregulin regulate the direction of mouse neural crest cell differentiationExperimental and Therapeutic Medicine2019
    2019 Histone demethylase KDM6B has an anti-tumorigenic function in neuroblastoma by promoting differentiationOncogenesis.  8. 2019
    2018 The CPLANE protein Intu protects kidneys from ischemia-reperfusion injury by targeting STAT1 for degradationNature Communications.  9. 2018
    2018 Atf3 deficiency promotes genome instability and spontaneous tumorigenesis in miceOncogene.  37:18-27. 2018
    2017 DNA methylation protects against cisplatin-induced kidney injury by regulating specific genes, including interferon regulatory factor 8Kidney International.  92:1194-1205. 2017
    2017 Epithelial-mesenchymal transition of ovarian cancer cells is sustained by Rac1 through simultaneous activation of MEK1/2 and Src signaling pathwaysOncogene.  36:1546-1558. 2017
    2017 Transcriptional Regulation of Stem Cell and Cancer Stem Cell MetabolismCurrent Stem Cell Reports.  3:19-27. 2017
    2016 Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming CellsCell Reports.  17:609-623. 2016
    2016 Loss of ATF3 promotes hormone-induced prostate carcinogenesis and the emergence of CK5 + CK8 + epithelial cellsOncogene.  35:3555-3564. 2016
    2016 Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1Neuro-Oncology.  18:819-829. 2016
    2016 Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstructionAutophagy.  12:976-998. 2016
    2016 Antibiotic drug tigecycline reduces neuroblastoma cells proliferation by inhibiting Akt activation in vitro and in vivo 2016
    2016 The stress-responsive gene ATF3 mediates dichotomous UV responses by regulating the Tip60 and p53 proteinsJournal of Biological Chemistry.  291:10847-10857. 2016
    2016 KDM4C and ATF4 Cooperate in Transcriptional Control of Amino Acid MetabolismCell Reports.  14:506-519. 2016
    2016 Triple negative breast cancer development can be selectively suppressed by sustaining an elevated level of cellular cyclic AMP through simultaneously blocking its efflux and decompositionOncotarget.  7:87232-87245. 2016
    2015 Loss of ATF3 promotes Akt activation and prostate cancer development in a Pten knockout mouse modelOncogene.  34:4975-4984. 2015
    2015 Internal Ribosome Entry Site-Based Bicistronic In Situ Reporter Assays for Discovery of Transcription-Targeted Lead Compounds 2015
    2015 The stress-responsive gene ATF3 regulates the histone acetyltransferase Tip60Nature Communications.  6. 2015
    2015 A novel Lozenge gene in silkworm, Bombyx mori regulates the melanization response of hemolymphDevelopmental and Comparative Immunology.  53:191-198. 2015
    2015 Cyclin-dependent kinase 2 is an ideal target for ovary tumors with elevated cyclin E1 expressionOncotarget.  6:20801-20812. 2015
    2015 Phox2B correlates with MYCN and is a prognostic marker for neuroblastoma developmentOncology Letters.  9:2507-2514. 2015
    2015 mTOR contributes to ER stress and associated apoptosis in renal tubular cells 2015
    2014 Genome-wide analysis of HOXC9-induced neuronal differentiation of neuroblastoma cellsGenomics Data.  2:50-52. 2014
    2014 MEIS2 is essential for neuroblastoma cell survival and proliferation by transcriptional control of M-phase progressionCell Death and Disease.  5. 2014
    2014 SHOX2 is a direct miR-375 target and a novel epithelial-to-mesenchymal transition inducer in breast cancer cellsNeoplasia.  16:279-290.e5. 2014
    2013 The histone H3 methyltransferase G9A epigenetically activates the serine-glycine synthesis pathway to sustain cancer cell survival and proliferationCell Metabolism.  18:896-907. 2013
    2013 HOXC9 directly regulates distinct sets of genes to coordinate diverse cellular processes during neuronal differentiationBMC Genomics.  14. 2013
    2013 Interleukin enhancer-binding factor 3 promotes breast tumor progression by regulating sustained urokinase-type plasminogen activator expressionOncogene.  32:3933-3943. 2013
    2013 Nek1 interacts with Ku80 to assist chromatin loading of replication factors and S-phase progressionCell Cycle.  12:2608-2616. 2013
    2013 Leflunomide Reduces Proliferation and Induces Apoptosis in Neuroblastoma Cells In Vitro and In VivoPLoS ONE.  8. 2013
    2013 Direct effects of Bmi1 on p53 protein stability inactivates oncoprotein stress responses in embryonal cancer precursor cells at tumor initiationOncogene.  32:3616-3626. 2013
    2013 Signaling by p38 MAPK stimulates nuclear localization of the microprocessor component p68 for processing of selected primary MicroRNAsScience Signaling.  6. 2013
    2013 COP1 and GSK3β cooperate to promote c-Jun degradation and inhibit breast cancer cell tumorigenesisNeoplasia.  15:1075-1085. 2013
    2012 Brain-selective kinase 2 (BRSK2) phosphorylation on PCTAIRE1 negatively regulates glucose-stimulated insulin secretion in pancreatic β-cellsJournal of Biological Chemistry.  287:30368-30375. 2012
    2012 Cyclin E1 is a common target of BMI1 and MYCN and a prognostic marker for neuroblastoma progressionOncogene.  31:3785-3795. 2012
    2012 Functional dissection of HOXD cluster genes in regulation of neuroblastoma cell proliferation and differentiationPLoS ONE.  7. 2012
    2012 NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumorsBMC Cancer.  12. 2012
    2012 Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemiaEpigenetics.  7:567-578. 2012
    2011 Na/K-ATPase mimetic pNaKtide peptide inhibits the growth of human cancer cellsJournal of Biological Chemistry.  286:32394-32403. 2011
    2011 HOXC8-Dependent Cadherin 11 Expression Facilitates Breast Cancer Cell Migration through Trio and RacGenes and Cancer.  2:880-888. 2011
    2011 HOXC9 links cell-cycle exit and neuronal differentiation and is a prognostic marker in neuroblastomaCancer Research.  71:4314-4324. 2011
    2010 Analysis of specialized DNA polymerases expression in human gliomas: Association with prognostic significanceNeuro-Oncology.  12:679-686. 2010
    2010 Loss of negative feedback control of nuclear factor-κB2 activity in lymphocytes leads to fatal lung inflammationAmerican Journal of Pathology.  176:2646-2657. 2010
    2009 MYCN promotes the expansion of Phox2B-positive neuronal progenitors to drive neuroblastoma developmentAmerican Journal of Pathology.  175:856-866. 2009
    2008 Nestin expression defines both glial and neuronal progenitors in postnatal sympathetic gangliaJournal of Comparative Neurology.  508:867-878. 2008
    2008 Constitutive production of NF-κB2 p52 is not tumorigenic but predisposes mice to inflammatory autoimmune disease by repressing Bim expressionJournal of Biological Chemistry.  283:10698-10706. 2008
    2007 NF-κB2 mutation targets TRAF1 to induce lymphomagenesisBlood.  110:743-751. 2007
    2007 Adeno-associated virus induces apoptosis during coinfection with adenovirusVirology.  358:391-401. 2007
    2007 Bmi-1 is essential for the tumorigenicity of neuroblastoma cellsAmerican Journal of Pathology.  170:1370-1378. 2007
    2006 NF-κB2 is required for the control of autoimmunity by regulating the development of medullary thymic epithelial cellsJournal of Biological Chemistry.  281:38617-38624. 2006
    2006 Bmi-1 regulates the differentiation and clonogenic self-renewal of I-type neuroblastoma cells in a concentration-dependent mannerJournal of Biological Chemistry.  281:34696-34704. 2006
    2005 Linking of N-Myc to death receptor machinery in neuroblastoma cellsJournal of Biological Chemistry.  280:9474-9481. 2005
    2002 p53 mediates DNA damaging drug-induced apoptosis through a caspase-9-dependent pathway in SH-SY5Y neuroblastoma cellsMolecular Cancer Therapeutics.  1:679-686. 2002
    2002 Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viabilityCell.  109:707-718. 2002
    2002 Induction of apoptosis in cancer: new therapeutic opportunitiesAnnals of Medicine.  34:451-469. 2002
    2002 NF-κB2 p100 is a pro-apoptotic protein with anti-oncogenic functionNature Cell Biology.  4:888-893. 2002
    2001 p53, Caspase 8, and Regulation of Apoptosis After Ionizing RadiationThe American journal of pediatric hematology/oncology.  23:185-188. 2001
    2000 Essential role for caspase-8 in transcription-independent apoptosis triggered by p53Journal of Biological Chemistry.  275:38905-38911. 2000
    1998 Oncogene-dependent regulation of caspase activation by p53 protein in a cell-free systemJournal of Biological Chemistry.  273:28378-28383. 1998
    1998 Lineage-specific signaling in melanocytes. c-Kit stimulation recruits p300/CBP to microphthalmiaJournal of Biological Chemistry.  273:17983-17986. 1998
    1998 Mechanisms of p53-Mediated Apoptosis 1998
    1997 Alleviation of historic H1-mediated transcriptional repression and chromatin compaction by the acidic activation region in chromosomal protein HMG-14Molecular and Cellular Biology.  17:5843-5855. 1997
    1994 Stimulation of RNA polymerase II elongation by chromosomal protein HMG-14Science.  265:796-799. 1994
    1994 The molar ratio of σ73 to core polymerase in the obligate intracellular bacterium, Rickettsia prowazekii 1994
    1993 Characterization of the DNA-melting function of the Rickettsia prowazekii RNA polymeraseJournal of Biological Chemistry.  268:3897-3902. 1993
    1990 Protective immunity induced in mice by detoxified salmonella lipopolysaccharideJournal of Medical Microbiology.  31:95-102. 1990
    1990 Purification and partial characterization of the DNA-dependent RNA polymerase from Rickettsia prowazekiiJournal of Bacteriology.  172:5624-5630. 1990

    Research Overview

  • 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.
  • Teaching Overview

  • My lectures cover cancer metabolism, biochemistry (the TCA cycle and amino acid metabolism), cell-cycle regulation, and apoptosis.
  • Education And Training

  • Doctor of Philosophy in Biomedical Sciences, University of South Alabama 1993
  • Master of Science in Microbiology and Immunology, Sun Yat-Sen University 1985
  • Bachelor's Level Degree in Medicine, Anhui Medical University 1982
  • Full Name

  • Han-Fei Ding