Genetics; Carcinoma, Hepatocellular; Lung Neoplasms; Melanoma; Pancreatic Neoplasms; Pathology; Disease Progression; Carcinogenesis; Phenomena and Processes
Obesity Research Working Group
Cancer is a complex disease and typically involves multiple gene-specific and global genetic and epigenetic changes in human genome. The major class of genes that has been causally linked to the process of tumorigenesis is tumor suppressors, which acts as a “breaks” and oncogenes, which functions as “accelerators” and typically promotes cancer. Recently, non-coding RNAs such as miRNAs and long non-coding RNAs are also linked to cancer wherein they can either promote or inhibit cancer cell growth. The focus of our lab is to understand the mechanisms of genetic and epigenetic regulation of cancer initiation and progression and translating this understanding for early detection and treatment of human cancers. We use melanoma, pancreatic cancer, lung cancer, hepatocellular carcinoma and hematological malignancies as model systems to study mechanism of tumor initiation and progression.
Specialized Terms: Genetic and epigenetic mechanisms of cancer initiation and progression
MELK promotes melanoma growth by stimulating the NF-kB pathway
Radoslav Janostiak, Navin Rauniyar, TuKiet T. Lam, Jianhong Ou, Lihua J. Zhu, Michael R. Green, and Narendra Wajapeyee, Cell Reports, 2017 Dec 5;21(10):2829-2841.
Paraoxonase 2 facilitates pancreatic cancer growth and metastasis by stimulating GLUT1-mediated glucose transport.
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Robert A. Cowles, Priti Kumar and Narendra Wajapeyee. Molecular Cell. 2017 Aug 17;67(4):685-701.e6. doi: 10.1016/j.molcel.2017.07.014. Epub 2017 Aug 10.
Serine hydroxymethyl transferase 1 stimulates pro-oncogenic cytokine expression through sialic acid to promote ovarian cancer tumor growth and progression.
Gupta R, Yang Q, Dogra SK, Wajapeyee N. Oncogene. 2017 Jul 13;36(28):4014-4024. doi: 10.1038/onc.2017.37. Epub 2017 Mar 13.
Interferon alpha-inducible protein 6 regulates NRASQ61K-induced melanomagenesis and growth.
Gupta R, Forloni M, Bisserier M, Dogra SK, Yang Q, Wajapeyee N. Elife. 2016 Sep 8;5. pii: e16432. doi: 10.7554/eLife.16432.
MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels.
Nagarajan A, Petersen MC, Nasiri AR, Butrico G, Fung A, Ruan HB, Kursawe R, Caprio S, Thibodeau J, Bourgeois-Daigneault MC, Sun L, Gao G, Bhanot S, Jurczak MJ, Green MR, Shulman GI, Wajapeyee N. Nature Communication. 2016 Aug 31;7:12639. doi: 10.1038/ncomms12639.
Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells.
Forloni M, Gupta R, Nagarajan A, Sun LS, Dong Y, Pirazzoli V, Toki M, Wurtz A, Melnick MA, Kobayashi S, Homer RJ, Rimm DL, Gettinger SJ, Politi K, Dogra SK, Wajapeyee N. Cell Reports 2016 Jul 12;16(2):457-471. doi: 10.1016/j.celrep.2016.05.087. Epub 2016 Jun 23.
LKB1 preserves genome integrity by stimulating BRCA1 expression.
Gupta R, Liu AY, Glazer PM, Wajapeyee N. Nucleic Acids Res. 2015 Jan;43(1):259-71. doi: 10.1093/nar/gku1294. Epub 2014 Dec 8.
TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein.
Bhatnagar S, Gazin C, Chamberlain L, Ou J, Zhu X, Tushir JS, Virbasius CM, Lin L, Zhu LJ, Wajapeyee N, Green MR. Nature. 2014 Dec 4;516(7529):116-20. doi: 10.1038/nature13955. Epub 2014 Nov 24.
Full List of PubMed Publications
- Janostiak R, Rauniyar N, Lam TT, Ou J, Zhu LJ, Green MR, Wajapeyee N: MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway. Cell Rep. 2017 Dec 5. PMID: 29212029
- Lizardi PM, Yan Q, Wajapeyee N: High-Throughput Deep Sequencing for Mapping Mammalian DNA Methylation. Cold Spring Harb Protoc. 2017 Dec 1; 2017 Dec 1. PMID: 27852842
- Lizardi PM, Yan Q, Wajapeyee N: Methyl-Cytosine-Based Immunoprecipitation for DNA Methylation Analysis. Cold Spring Harb Protoc. 2017 Dec 1; 2017 Dec 1. PMID: 27852840
- Lizardi PM, Yan Q, Wajapeyee N: Analysis of DNA Methylation in Mammalian Cells. Cold Spring Harb Protoc. 2017 Dec 1; 2017 Dec 1. PMID: 27852839
- Lizardi PM, Yan Q, Wajapeyee N: Methylation-Specific Polymerase Chain Reaction (PCR) for Gene-Specific DNA Methylation Detection. Cold Spring Harb Protoc. 2017 Dec 1; 2017 Dec 1. PMID: 27852838
- Lizardi PM, Yan Q, Wajapeyee N: DNA Bisulfite Sequencing for Single-Nucleotide-Resolution DNA Methylation Detection. Cold Spring Harb Protoc. 2017 Nov 1; 2017 Nov 1. PMID: 27852843
- Lizardi PM, Yan Q, Wajapeyee N: Illumina Sequencing of Bisulfite-Converted DNA Libraries. Cold Spring Harb Protoc. 2017 Nov 1; 2017 Nov 1. PMID: 27852841
- Politi K, Wajapeyee N: Genome-Wide RNA Interference: Functional Genomics in the Postgenomics Era. Cold Spring Harb Protoc. 2017 Sep 1; 2017 Sep 1. PMID: 28864574
- Nagarajan A, Dogra SK, Sun L, Gandotra N, Ho T, Cai G, Cline G, Kumar P, Cowles RA, Wajapeyee N: Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport. Mol Cell. 2017 Aug 17; 2017 Aug 10. PMID: 28803777
- Gupta R, Wajapeyee N: Transcriptional Analysis-Based Integrative Genomics Approach to Identify Tumor-Promoting Metabolic Genes. Methods Mol Biol. 2017. PMID: 27832547
- Forloni M, Ho T, Sun L, Wajapeyee N: Large-Scale RNA Interference Screening to Identify Transcriptional Regulators of a Tumor Suppressor Gene. Methods Mol Biol. 2017. PMID: 27832546
- Gupta R, Forloni M, Bisserier M, Dogra SK, Yang Q, Wajapeyee N: Interferon alpha-inducible protein 6 regulates NRASQ61K-induced melanomagenesis and growth. Elife. 2016 Sep 8; 2016 Sep 8. PMID: 27608486
- Nagarajan A, Petersen MC, Nasiri AR, Butrico G, Fung A, Ruan HB, Kursawe R, Caprio S, Thibodeau J, Bourgeois-Daigneault MC, Sun L, Gao G, Bhanot S, Jurczak MJ, Green MR, Shulman GI, Wajapeyee N: MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels. Nat Commun. 2016 Aug 31; 2016 Aug 31. PMID: 27577745
- Forloni M, Gupta R, Nagarajan A, Sun LS, Dong Y, Pirazzoli V, Toki M, Wurtz A, Melnick MA, Kobayashi S, Homer RJ, Rimm DL, Gettinger SJ, Politi K, Dogra SK, Wajapeyee N: Oncogenic EGFR Represses the TET1 DNA Demethylase to Induce Silencing of Tumor Suppressors in Cancer Cells. Cell Rep. 2016 Jul 12; 2016 Jun 23. PMID: 27346347
- Nagarajan A, Malvi P, Wajapeyee N: Oncogene-directed alterations in cancer cell metabolism. Trends Cancer. 2016 Jul; 2016 Jun 27. PMID: 27822561
- Gupta R, Liu AY, Glazer PM, Wajapeyee N: LKB1 preserves genome integrity by stimulating BRCA1 expression. Nucleic Acids Res. 2015 Jan; 2014 Dec 8. PMID: 25488815
- Bhatnagar S, Gazin C, Chamberlain L, Ou J, Zhu X, Tushir JS, Virbasius CM, Lin L, Zhu LJ, Wajapeyee N, Green MR: TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein. Nature. 2014 Dec 4; 2014 Nov 24. PMID: 25470042
- Lin L, Chamberlain L, Pak ML, Nagarajan A, Gupta R, Zhu LJ, Wright CM, Fong KM, Wajapeyee N, Green MR: A large-scale RNAi-based mouse tumorigenesis screen identifies new lung cancer tumor suppressors that repress FGFR signaling. Cancer Discov. 2014 Oct; 2014 Jul 11. PMID: 25015643
- Bhatnagar S, Zhu X, Ou J, Lin L, Chamberlain L, Zhu LJ, Wajapeyee N, Green MR: Genetic and pharmacological reactivation of the mammalian inactive X chromosome. Proc Natl Acad Sci U S A. 2014 Sep 2; 2014 Aug 18. PMID: 25136103
- Gupta R, Dong Y, Solomon PD, Wettersten HI, Cheng CJ, Min JN, Henson J, Dogra SK, Hwang SH, Hammock BD, Zhu LJ, Reddel RR, Saltzman WM, Weiss RH, Chang S, Green MR, Wajapeyee N: Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proc Natl Acad Sci U S A. 2014 Jul 29; 2014 Jul 14. PMID: 25024194
- Lu Y, Wajapeyee N, Turker MS, Glazer PM: Silencing of the DNA mismatch repair gene MLH1 induced by hypoxic stress in a pathway dependent on the histone demethylase LSD1. Cell Rep. 2014 Jul 24; 2014 Jul 17. PMID: 25043185
- Nagarajan A, Dogra SK, Liu AY, Green MR, Wajapeyee N: PEA15 regulates the DNA damage-induced cell cycle checkpoint and oncogene-directed transformation. Mol Cell Biol. 2014 Jun; 2014 Apr 7. PMID: 24710276
- Forloni M, Dogra SK, Dong Y, Conte D Jr, Ou J, Zhu LJ, Deng A, Mahalingam M, Green MR, Wajapeyee N: miR-146a promotes the initiation and progression of melanoma by activating Notch signaling. Elife. 2014 Feb 18; 2014 Feb 18. PMID: 24550252
- Nagarajan A, Roden C, Wajapeyee N: Reduced representation bisulfite sequencing to identify global alteration of DNA methylation. Methods Mol Biol. 2014. PMID: 25030916
- Wajapeyee N, Malonia SK, Palakurthy RK, Green MR: Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors. Genes Dev. 2013 Oct 15; 2013 Oct 8. PMID: 24105743
- Fang M, Xia F, Mahalingam M, Virbasius CM, Wajapeyee N, Green MR: MEN1 is a melanoma tumor suppressor that preserves genomic integrity by stimulating transcription of genes that promote homologous recombination-directed DNA repair. Mol Cell Biol. 2013 Jul; 2013 May 6. PMID: 23648481
- Gupta R, Wajapeyee N: Induction of cellular senescence by oncogenic RAS. Methods Mol Biol. 2013. PMID: 23929102
- Wajapeyee N, Deibler SK, Green MR: Genome-wide RNAi screening to identify regulators of oncogene-induced cellular senescence. Methods Mol Biol. 2013. PMID: 23296672
- Lizardi PM, Forloni M, Wajapeyee N: Genome-wide approaches for cancer gene discovery. Trends Biotechnol. 2011 Nov; 2011 Jul 13. PMID: 21757246
- Wajapeyee N, Green MR: Induction of senescence in melanoma: thinking outside the cell. Pigment Cell Melanoma Res. 2011 Oct. PMID: 22081810
- Gupta R, Nagarajan A, Wajapeyee N: Advances in genome-wide DNA methylation analysis. Biotechniques. 2010 Oct. PMID: 20964631
- Muthusamy V, Bosenberg M, Wajapeyee N: Redefining regulation of DNA methylation by RNA interference. Genomics. 2010 Oct; 2010 Jul 8. PMID: 20620207
- Wajapeyee N, Wang SZ, Serra RW, Solomon PD, Nagarajan A, Zhu X, Green MR: Senescence induction in human fibroblasts and hematopoietic progenitors by leukemogenic fusion proteins. Blood. 2010 Jun 17; 2010 Apr 26. PMID: 20421454
- Decarlo K, Yang S, Emley A, Wajapeyee N, Green M, Mahalingam M: Oncogenic BRAF-positive dysplastic nevi and the tumor suppressor IGFBP7--challenging the concept of dysplastic nevi as precursor lesions? Hum Pathol. 2010 Jun; 2010 Mar 16. PMID: 20233623
- Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR: Role for IGFBP7 in senescence induction by BRAF. Cell. 2010 May 28. PMID: 20510919
- Emley A, Yang S, Wajapeyee N, Green MR, Mahalingam M: Oncogenic BRAF and the tumor suppressor IGFBP7 in the genesis of atypical spitzoid nevomelanocytic proliferations. J Cutan Pathol. 2010 Mar; 2009 Sep 24. PMID: 19788444
- Yan Q, Wajapeyee N: Exploiting cellular senescence to treat cancer and circumvent drug resistance. Cancer Biol Ther. 2010 Feb; 2010 Feb 11. PMID: 20118655
- Wajapeyee N, Kapoor V, Mahalingam M, Green MR: Efficacy of IGFBP7 for treatment of metastatic melanoma and other cancers in mouse models and human cell lines. Mol Cancer Ther. 2009 Nov; 2009 Oct 27. PMID: 19861408
- Palakurthy RK, Wajapeyee N, Santra MK, Gazin C, Lin L, Gobeil S, Green MR: Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression. Mol Cell. 2009 Oct 23. PMID: 19854132
- Santra MK, Wajapeyee N, Green MR: F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage. Nature. 2009 Jun 4; 2009 May 3. PMID: 19412162
- Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR: Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 2008 Feb 8. PMID: 18267069
- Gazin C, Wajapeyee N, Gobeil S, Virbasius CM, Green MR: An elaborate pathway required for Ras-mediated epigenetic silencing. Nature. 2007 Oct 25. PMID: 17960246
- Wajapeyee N, Britto R, Ravishankar HM, Somasundaram K: Apoptosis induction by activator protein 2alpha involves transcriptional repression of Bcl-2. J Biol Chem. 2006 Jun 16; 2006 Mar 13. PMID: 16533807
- Wajapeyee N, Raut CG, Somasundaram K: Activator protein 2alpha status determines the chemosensitivity of cancer cells: implications in cancer chemotherapy. Cancer Res. 2005 Oct 1. PMID: 16204029
- Joseph J, Wajapeyee N, Somasundaram K: Role of p53 status in chemosensitivity determination of cancer cells against histone deacetylase inhibitor sodium butyrate. Int J Cancer. 2005 May 20. PMID: 15688418
- Wajapeyee N, Somasundaram K: Pharmacogenomics in breast cancer: current trends and future directions. Curr Opin Mol Ther. 2004 Jun. PMID: 15264432
- Wajapeyee N, Somasundaram K: Cell cycle arrest and apoptosis induction by activator protein 2alpha (AP-2alpha) and the role of p53 and p21WAF1/CIP1 in AP-2alpha-mediated growth inhibition. J Biol Chem. 2003 Dec 26; 2003 Oct 9. PMID: 14551210
- Somasundaram K, Das S, Lakhotia S, Wajapeyee N: Analysis of gene promoter regulation by tumor suppressor genes. Methods Mol Biol. 2003. PMID: 12777723