Gangning Liang, MD, PhD

Dr. Gangning Liang is a Professor of Department of Urology and Director of Epigenetic Translational Research of USC Institute of Urology at Norris Comprehensive Cancer Center. He obtained his MD degree from Shanghai Second Medical School in 1985 and received PhD degree from Department of Pharmaceutical Science in University of Nebraska Medical Center in 1995. He was appointed Assistant Professor in 1998, Associate Professor in 2008, and Professor in 2016 in USC Norris Comprehensive Cancer Center. He completed a postdoctoral training in Epigenetics with Dr. Peter A. Jones 1995-1998 at USC. His research interests include investigating epigenome structures, epigenomic alterations during tumorigenesis, and epigenetic alterations induced by drug treatment in cancer therapies. As PI, multiple-PI, and co-Investigator over 10 NIH-funded grants, his research has laid the groundwork for the proposed research project including the roles of DNA methyltransferases (DNMTs) and microRNAs during tumorigenesis and novel methods of characterizing epigenetic changes and monitoring these changes in patients. In this regard, he has identified epigenetic alterations in urine sediments for bladder cancer-based diagnostic and prognostic purposes, more recently he also is also developing similar assay in kidney and prostate cancer, as well as introducing epigenetic therapy for cancer treatment in preclinical models. He is currently using these techniques and models, which he developed, to not only to further study the role of epigenetic regulation during tumorigenesis, but also to establish new translational projects that directly address clinical questions. He is focusing on his translational research to use epigenetic alteration as foundation to identify drug targets in a selective and predictable way for precision cancer medicine and to improve in patient survival and quality of life. He published extensively in journals including Cell, Cancer Cell, Molecular Cell, Genome Research, Hepatology, Nature Communications, Genome Biology, PNAS, Cancer Research, and Oncogene with over 100 peer reviewed articles.

• Albumin levels predict prognosis in advanced renal cell carcinoma treated with tyrosine kinase inhibitors: a systematic review and meta-analysisUrol Oncol. 2022 01; 40(1):12. e13-12. e22. . View in PubMed
• MMP-9-dependent proteolysis of the histone H3 N-terminal tail: a critical epigenetic step in driving oncogenic transcription and colon tumorigenesis Mol Oncol. 2024 Apr 10. . View in PubMed
• VprBP/DCAF1 Triggers Melanomagenic Gene Silencing through Histone H2A Phosphorylation Biomedicines. 2023 Sep 17; 11(9). . View in PubMed
• VprBP/DCAF1 triggers melanomagenic gene silencing through histone H2A phosphorylation Res Sq. 2023 Jul 12. . View in PubMed
• A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Prospective Cohort Study J Urol. 2023 05; 209(5):854-862. . View in PubMed
• Reply by Authors J Urol. 2023 05; 209(5):862. . View in PubMed
• RNA mis-splicing drives viral mimicry response after DNMTi therapy in SETD2-mutant kidney cancer Cell Rep. 2023 01 31; 42(1):112016. . View in PubMed
• SETD2 Deficiency Confers Sensitivity to Dual Inhibition of DNA Methylation and PARP in Kidney Cancer Cancer Res. 2023 11 15; 83(22):3813-3826. . View in PubMed
• FOXC1 Binds Enhancers and Promotes Cisplatin Resistance in Bladder Cancer Cancers (Basel). 2022 Mar 28; 14(7). . View in PubMed
• Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy Nat Commun. 2022 09 21; 13(1):5523. . View in PubMed
• DNMT and EZH2 inhibitors synergize to activate therapeutic targets in hepatocellular carcinoma Cancer Lett. 2022 11 01; 548:215899. . View in PubMed
• The Role of DNA Methylation and DNA Methyltransferases in Cancer Adv Exp Med Biol. 2022; 1389:317-348. . View in PubMed
• Characterizing DNA methylation signatures and their potential functional roles in Merkel cell carcinoma Genome Med. 2021 08 16; 13(1):130. . View in PubMed
• Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer J Immunother Cancer. 2020 11; 8(2). . View in PubMed
• Epigenetic plasticity potentiates a rapid cyclical shift to and from an aggressive cancer phenotype Int J Cancer. 2020 06 01; 146(11):3065-3076. . View in PubMed
• Telomerase Variants in Patients with Cirrhosis Awaiting Liver Transplantation Hepatology. 2019 06; 69(6):2652-2663. . View in PubMed
• Impact of polymorphisms within genes involved in regulating DNA methylation in patients with metastatic colorectal cancer enrolled in three independent, randomised, open-label clinical trials: a meta-analysis from TRIBE, MAVERICC and FIRE-3 Eur J Cancer. 2019 04; 111:138-147. . View in PubMed
• AMPK variant, a candidate of novel predictor for chemotherapy in metastatic colorectal cancer: A meta-analysis using TRIBE, MAVERICC and FIRE3 Int J Cancer. 2019 10 15; 145(8):2082-2090. . View in PubMed
• The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome Genes (Basel). 2019 02 23; 10(2). . View in PubMed
• Data integration by multi-tuning parameter elastic net regression BMC Bioinformatics. 2018 Oct 10; 19(1):369. . View in PubMed
• Quantitative Contour Analysis as an Image-based Discriminator Between Benign and Malignant Renal Tumors Urology. 2018 Apr; 114:121-127. . View in PubMed
• Integrative Epigenetic Analysis Reveals Therapeutic Targets to the DNA Methyltransferase Inhibitor Guadecitabine (SGI-110) in Hepatocellular Carcinoma Hepatology. 2018 10; 68(4):1412-1428. . View in PubMed
• DNA methylation aberrancies delineate clinically distinct subsets of colorectal cancer and provide novel targets for epigenetic therapies Oncogene. 2018 02 01; 37(5):566-577. . View in PubMed
• Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers Oncotarget. 2017 Jan 17; 8(3):5439-5448. . View in PubMed
• Down-regulation of ARID1A is sufficient to initiate neoplastic transformation along with epigenetic reprogramming in non-tumorigenic endometriotic cells Cancer Lett. 2017 08 10; 401:11-19. . View in PubMed
• Nucleosome Positioning and NDR Structure at RNA Polymerase III Promoters Sci Rep. 2017 02 08; 7:41947. . View in PubMed
• Identifying aggressive prostate cancer foci using a DNA methylation classifier Genome Biol. 2017 01 12; 18(1):3. . View in PubMed
• Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients Sci Rep. 2017 01 13; 7:40636. . View in PubMed
• DNA methylation aberrancies as a guide for surveillance and treatment of human cancers Epigenetics. 2017 06 03; 12(6):416-432. . View in PubMed
• epiG: statistical inference and profiling of DNA methylation from whole-genome bisulfite sequencing data Genome Biol. 2017 02 21; 18(1):38. . View in PubMed
• Genetic and Epigenetic Alterations in Bladder Cancer Int Neurourol J. 2016 Nov; 20(Suppl 2):S84-94. . View in PubMed
• Isoform switching and exon skipping induced by the DNA methylation inhibitor 5-Aza-2′-deoxycytidine Sci Rep. 2016 Apr 19; 6:24545. . View in PubMed
• DNMT3B isoforms without catalytic activity stimulate gene body methylation as accessory proteins in somatic cells Nat Commun. 2016 04 28; 7:11453. . View in PubMed
• Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine Proc Natl Acad Sci U S A. 2016 09 13; 113(37):10238-44. . View in PubMed
• Identification of DNA Methylation-Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma Cancer Res. 2016 04 01; 76(7):1954-64. . View in PubMed
• Bivalent Regions of Cytosine Methylation and H3K27 Acetylation Suggest an Active Role for DNA Methylation at Enhancers Mol Cell. 2016 05 05; 62(3):422-431. . View in PubMed
• The Role of DNA Methylation in Cancer Adv Exp Med Biol. 2016; 945:151-172. . View in PubMed
• Linker histone H12 establishes chromatin compaction and gene silencing through recognition of H3K27me3. Sci Rep. 2015 Nov 19; 5:16714. . View in PubMed
• Hypermethylation of the VTRNA1-3 Promoter is Associated with Poor Outcome in Lower Risk Myelodysplastic Syndrome Patients Genes (Basel). 2015 Oct 14; 6(4):977-90. . View in PubMed
• Unique Role for a DNA Methyltransferase Isoform in Lung Cancer EBioMedicine. 2015 Oct; 2(10):1272-3. . View in PubMed
• CT prediction of the Fuhrman grade of clear cell renal cell carcinoma (RCC): towards the development of computer-assisted diagnostic method Abdom Imaging. 2015 Oct; 40(8):3168-74. . View in PubMed
• DNA-Demethylating Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts Cell. 2015 Aug 27; 162(5):961-73. . View in PubMed
• Outlining the limits of partial nephrectomy Transl Androl Urol. 2015 Jun; 4(3):294-300. . View in PubMed
• Gene body methylation can alter gene expression and is a therapeutic target in cancer Cancer Cell. 2014 Oct 13; 26(4):577-90. . View in PubMed
• Epigenetic alterations and microRNA misexpression in cancer and autoimmune diseases: a critical review Clin Rev Allergy Immunol. 2014 Oct; 47(2):128-35. . View in PubMed
• Reprogramming of the human intestinal epigenome by surgical tissue transposition Genome Res. 2014 Apr; 24(4):545-53. . View in PubMed
• A panel of three markers hyper- and hypomethylated in urine sediments accurately predicts bladder cancer recurrence Clin Cancer Res. 2014 Apr 01; 20(7):1978-89. . View in PubMed
• miR-30d, miR-181a and miR-199a-5p cooperatively suppress the endoplasmic reticulum chaperone and signaling regulator GRP78 in cancer Oncogene. 2013 Sep 26; 32(39):4694-701. . View in PubMed
• Alterations in deoxyribonucleic acid (DNA) methylation patterns of Calca, Timp3, Mmp2, and Igf2r are associated with chronic cystitis in a cyclophosphamide-induced mouse modelUrology. 2013 Jul; 82(1):253. e9-15. . View in PubMed
• Diagnostic markers of urothelial cancer based on DNA methylation analysis BMC Cancer. 2013 Jun 04; 13:275. . View in PubMed
• SNF5 is an essential executor of epigenetic regulation during differentiation PLoS Genet. 2013 Apr; 9(4):e1003459. . View in PubMed
• Functional DNA demethylation is accompanied by chromatin accessibility Nucleic Acids Res. 2013 Apr; 41(7):3973-85. . View in PubMed
• Nucleosome occupancy and gene regulation during tumorigenesis Adv Exp Med Biol. 2013; 754:109-34. . View in PubMed
• Synergistic re-activation of epigenetically silenced genes by combinatorial inhibition of DNMTs and LSD1 in cancer cells PLoS One. 2013; 8(9):e75136. . View in PubMed
• Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules Genome Res. 2012 Dec; 22(12):2497-506. . View in PubMed
• DNA methylation screening identifies driver epigenetic events of cancer cell survival Cancer Cell. 2012 May 15; 21(5):655-667. . View in PubMed
• Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells Epigenetics Chromatin. 2012 Jan 27; 5(1):3. . View in PubMed
• Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q311 predict outcome in AML. Blood. 2012 Jan 05; 119(1):206-16. . View in PubMed
• Gene reactivation by 5-aza-2′-deoxycytidine-induced demethylation requires SRCAP-mediated H2AZ insertion to establish nucleosome depleted regions. PLoS Genet. 2012; 8(3):e1002604. . View in PubMed
• Epigenetic alterations in bladder cancer and their potential clinical implications Adv Urol. 2012; 2012:546917. . View in PubMed
• Polycomb-repressed genes have permissive enhancers that initiate reprogramming Cell. 2011 Dec 09; 147(6):1283-94. . View in PubMed
• DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoter Hum Mol Genet. 2011 Nov 15; 20(22):4299-310. . View in PubMed
• OCT4 establishes and maintains nucleosome-depleted regions that provide additional layers of epigenetic regulation of its target genes Proc Natl Acad Sci U S A. 2011 Aug 30; 108(35):14497-502. . View in PubMed
• Creating a flexible multiple microRNA expression vector by linking precursor microRNAs Biochem Biophys Res Commun. 2011 Jul 29; 411(2):276-80. . View in PubMed
• Conditional inactivation of the CXCR4 receptor in osteoprecursors reduces postnatal bone formation due to impaired osteoblast development J Biol Chem. 2011 Jul 29; 286(30):26794-805. . View in PubMed
• Epigenetic reprogramming as a key contributor to melanocyte malignant transformation Epigenetics. 2011 Apr; 6(4):450-64. . View in PubMed
• Nucleosomes containing methylated DNA stabilize DNA methyltransferases 3A/3B and ensure faithful epigenetic inheritance PLoS Genet. 2011 Feb 03; 7(2):e1001286. . View in PubMed
• Unique DNA methylation patterns distinguish noninvasive and invasive urothelial cancers and establish an epigenetic field defect in premalignant tissue Cancer Res. 2010 Oct 15; 70(20):8169-78. . View in PubMed
• Equitoxic doses of 5-azacytidine and 5-aza-2’deoxycytidine induce diverse immediate and overlapping heritable changes in the transcriptome PLoS One. 2010 Sep 29; 5(9). . View in PubMed
• H2AZ maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes. Mol Cell. 2010 Sep 24; 39(6):901-11. . View in PubMed
• Hypomethylation of a LINE-1 promoter activates an alternate transcript of the MET oncogene in bladders with cancer PLoS Genet. 2010 Apr 22; 6(4):e1000917. . View in PubMed
• Tissue inhibitor of metalloproteinase 1 expression associated with gene demethylation confers anoikis resistance in early phases of melanocyte malignant transformation Transl Oncol. 2009 Dec; 2(4):329-40. . View in PubMed
• Selective anchoring of DNA methyltransferases 3A and 3B to nucleosomes containing methylated DNA Mol Cell Biol. 2009 Oct; 29(19):5366-76. . View in PubMed
• The tumor suppressor microRNA-101 becomes an epigenetic player by targeting the polycomb group protein EZH2 in cancer Cell Cycle. 2009 Aug; 8(15):2313-4. . View in PubMed
• Changes in DNA methylation of tandem DNA repeats are different from interspersed repeats in cancer Int J Cancer. 2009 Aug 01; 125(3):723-9. . View in PubMed
• DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation Mol Cancer Ther. 2009 Jun; 8(6):1579-88. . View in PubMed
• The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2 Cancer Res. 2009 Mar 15; 69(6):2623-9. . View in PubMed
• Epigenetic therapy upregulates the tumor suppressor microRNA-126 and its host gene EGFL7 in human cancer cells Biochem Biophys Res Commun. 2009 Feb 13; 379(3):726-31. . View in PubMed
• Rethinking how DNA methylation patterns are maintained Nat Rev Genet. 2009 11; 10(11):805-11. . View in PubMed
• Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line Proc Natl Acad Sci U S A. 2008 Sep 02; 105(35):12979-84. . View in PubMed
• RUNX3 methylation reveals that bladder tumors are older in patients with a history of smoking Cancer Res. 2008 Aug 01; 68(15):6208-14. . View in PubMed
• DNA methylation analysis by digital bisulfite genomic sequencing and digital MethyLight Nucleic Acids Res. 2008 Aug; 36(14):4689-98. . View in PubMed
• Examination of IGF2 and H19 loss of imprinting in bladder cancer Cancer Res. 2007 Nov 15; 67(22):10753-8. . View in PubMed
• Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island Cancer Cell. 2007 Nov; 12(5):432-44. . View in PubMed
• Delivery of 5-aza-2′-deoxycytidine to cells using oligodeoxynucleotides Cancer Res. 2007 Jul 01; 67(13):6400-8. . View in PubMed
• Methylation-sensitive single-nucleotide primer extension (Ms-SNuPE) for quantitative measurement of DNA methylation Nat Protoc. 2007; 2(8):1931-6. . View in PubMed
• Locus-wide chromatin remodeling and enhanced androgen receptor-mediated transcription in recurrent prostate tumor cells Mol Cell Biol. 2006 Oct; 26(19):7331-41. . View in PubMed
• Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival Proc Natl Acad Sci U S A. 2006 Sep 19; 103(38):14080-5. . View in PubMed
• Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells Cancer Cell. 2006 Jun; 9(6):435-43. . View in PubMed
• Prognostic relevance of methylation markers in patients with non-muscle invasive bladder carcinoma Eur J Cancer. 2005 Nov; 41(17):2769-78. . View in PubMed
• Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer Nat Clin Pract Urol. 2005 Oct; 2(10):502-10. . View in PubMed
• Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine Mol Cancer Ther. 2005 Oct; 4(10):1515-20. . View in PubMed
• Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients Clin Cancer Res. 2004 Nov 15; 10(22):7457-65. . View in PubMed
• Preferential response of cancer cells to zebularine Cancer Cell. 2004 Aug; 6(2):151-8. . View in PubMed
• Epigenetics in human disease and prospects for epigenetic therapy Nature. 2004 May 27; 429(6990):457-63. . View in PubMed
• Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome Proc Natl Acad Sci U S A. 2004 May 11; 101(19):7357-62. . View in PubMed
• Continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells Mol Cell Biol. 2004 Feb; 24(3):1270-8. . View in PubMed
• Role of the DNA methyltransferase variant DNMT3b3 in DNA methylation Mol Cancer Res. 2004 Jan; 2(1):62-72. . View in PubMed
• Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine Cancer Res. 2002 Nov 15; 62(22):6456-61. . View in PubMed
• Hypomethylation and hypermethylation of DNA in Wilms tumors Oncogene. 2002 Sep 26; 21(43):6694-702. . View in PubMed
• Identification and characterization of alternatively spliced variants of DNA methyltransferase 3a in mammalian cells Gene. 2002 Sep 18; 298(1):91-9. . View in PubMed
• Identification of DNA methylation differences during tumorigenesis by methylation-sensitive arbitrarily primed polymerase chain reaction Methods. 2002 Jun; 27(2):150-5. . View in PubMed
• Analysis of gene induction in human fibroblasts and bladder cancer cells exposed to the methylation inhibitor 5-aza-2′-deoxycytidine Cancer Res. 2002 Feb 15; 62(4):961-6. . View in PubMed
• Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements Mol Cell Biol. 2002 Jan; 22(2):480-91. . View in PubMed
• Susceptibility of nonpromoter CpG islands to de novo methylation in normal and neoplastic cells J Natl Cancer Inst. 2001 Oct 03; 93(19):1465-72. . View in PubMed
• Global and gene-specific epigenetic patterns in human bladder cancer genomes are relatively stable in vivo and in vitro over time Cancer Res. 2001 Aug 01; 61(15):5875-84. . View in PubMed
• The endothelin receptor B (EDNRB) promoter displays heterogeneous, site specific methylation patterns in normal and tumor cells Hum Mol Genet. 2001 Apr 15; 10(9):903-10. . View in PubMed
• The gene for a novel transmembrane protein containing epidermal growth factor and follistatin domains is frequently hypermethylated in human tumor cells Cancer Res. 2000 Sep 01; 60(17):4907-12. . View in PubMed
• PAX6 methylation and ectopic expression in human tumor cells Int J Cancer. 2000 Jul 15; 87(2):179-85. . View in PubMed
• Progressive increases in de novo methylation of CpG islands in bladder cancer Cancer Res. 2000 May 01; 60(9):2473-6. . View in PubMed
• DNA methylator and mismatch repair phenotypes are not mutually exclusive in colorectal cancer cell lines Oncogene. 2000 Feb 17; 19(7):943-52. . View in PubMed
• Relationship between transcription and DNA methylation Curr Top Microbiol Immunol. 2000; 249:75-86. . View in PubMed
• The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors Nucleic Acids Res. 1999 Jun 01; 27(11):2291-8. . View in PubMed
• Novel endothelin B receptor transcripts with the potential of generating a new receptor Gene. 1999 Mar 04; 228(1-2):43-9. . View in PubMed
• DNA methylation differences associated with tumor tissues identified by genome scanning analysis Genomics. 1998 Nov 01; 53(3):260-8. . View in PubMed
• Regioselective effect of zwitterionic DNA substitutions on DNA alkylation: evidence for a strong side chain orientational preference Biochemistry. 1997 May 20; 36(20):6024-32. . View in PubMed
• Identification and characterization of differentially methylated regions of genomic DNA by methylation-sensitive arbitrarily primed PCR Cancer Res. 1997 Feb 15; 57(4):594-9. . View in PubMed
• Reaction of N-(2-chloroethyl)-N-nitrosoureas with DNA: effect of buffers on DNA adduction, cross-linking, and cytotoxicity Chem Res Toxicol. 1996 Jan-Feb; 9(1):208-14. . View in PubMed
• The use of 2-hydroperoxytetrahydrofuran as a reagent to sequence cytosine and to probe non-Watson-Crick DNA structures Nucleic Acids Res. 1995 Feb 25; 23(4):713-9. . View in PubMed

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• Lenz, Heinz-Josef
• Weisenberger, Daniel
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• Siegmund, Kimberly
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