Samson T. Jacob

Another research area deals with elucidation of the molecular mechanisms by which DNA methylation silences genes, particularly tumor suppressor genes, which can be effectively used to re-activate the silenced genes and consequently reverse the tumorigenic process.

A third research focus is to extend our initial observation on a novel molecular mechanism of action of 5-aza cytidine/5’aza 3’deoxycytidine, and use this strategy to identify novel DNA hypomethylating agents that selectively degrade the maintenance DNA methyltransferase DNMT1 by proteasomal pathway with minimal effects on DNA replication .This approach should generate agents that exhibit markedly reduced toxic effects of the commonly used agents for DNA demethylation in Epigenetic Cancer Therapy.

Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST and Patel T (2007) "MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer" Gastroenterology 133(2):647-58.

Bai S, Datta J, Jacob ST and Ghoshal K (2007) "Treatment of PC12 cells with nerve growth factor induces proteasomal degradation of T-cadherin that requires tyrosine phosphorylation of its cadherin domain" J Biol Chem. 282(37):27171-80.

Pal S, Baiocchi RA, Byrd JC, Grever MR, Jacob ST and Sif S (2007) "Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma" EMBO J. 26(15):3558-69.

Motiwala T, Majumder S, Kutay H, Smith DS, Neuberg DS, Lucas DM, Byrd JC, Grever M and Jacob ST (2007) "Methylation and silencing of protein tyrosine phosphatase receptor type O in chronic lymphocytic leukemia" Clin Cancer Res. 13(11):3174-81.

Datta J, Majumder S, Kutay H, Motiwala T, Frankel W, Costa R, Cha HC, MacDougald OA, Jacob ST and Ghoshal K (2006) "Metallothionein expression is suppressed in primary human hepatocellular carcinomas and is mediated through inactivation of CCAAT/enhancer binding protein alpha by phosphatidylinositol 3-kinase signaling cascade" Cancer Res 67(6):2736-46.

Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, Jacob ST and Ghoshal K (2006) "Downregulation of miR-122 in the rodent and human hepatocellular carcinomas" J Cell Biochem 99(3):671-8.

Motiwala T and Jacob ST (2006) "Progress in Nucleic Acid Research and Molecular Biology" Prog Nucleic Acid Res Mol Biol. 81:297-329.

Ghoshal K, Li X, Datta J, Bai S, Pogribny I, Pogribny M, Huang Y, Young D and Jacob ST (2006) "A folate- and methyl-deficient diet alters the expression of DNA methyltransferases and methyl CpG binding proteins involved in epigenetic gene silencing in livers of F344 rats" J Nutr 136(6):1522-7.

Majumder S, Kutay H, Datta J, Summers D and Jacob ST (2006) "Epigenetic regulation of metallothionein-i gene expression: differential regulation of methylated and unmethylated promoters by DNA methyltransferases and methyl CpG binding proteins" J Cell Biochem 97(6):1300-16.

Majumder S, Ghoshal K, Datta J, Smith DS, Bai S and Jacob ST (2006) "Role of DNA Methyltransferases in Regulation of Human Ribosomal RNA Gene Transcription" J Biol Chem 281(31):22062-72.

Bai S, Ghoshal K and Jacob ST (2006) "Identification of T-cadherin as a novel target of DNA methyltransferase 3B and its role in the suppression of NGF-mediated neurite outgrowth in PC12 cells" J Biol Chem 281(19):13604-11.

Datta J, Majumder S, Bai S, Ghoshal K, Kutay H, Smith DS, Crabb JW and Jacob ST (2005) "Physical and functional interaction of DNA methyltransferase 3A with Mbd3 and Brg1 in mouse lymphosarcoma cells" Cancer Res 23:10891-900.

Ren C, Zhang L, Freitas MA, Ghoshal K, Parthun MR and Jacob ST (2005) "Peptide mass mapping of acetylated isoforms of histone H4 from mouse lymphosarcoma cells treated with histone deacetylase (HDACs) inhibitors" J Am Soc Mass 10:1641-53.

Ghoshal K, Datta J, Majumder S, Bai S, Kutay H, Motiwala T and Jacob ST (2005)"5-Aza-deoxycytidine induces selective degradation of DNA methyltransferase 1 by a proteasomal pathway that requires the KEN box, bromo-adjacent homology domain, and nuclear localization signal" Mol Cell Biol 11:4727-41.

Jacob ST and Motiwala T (2005) "Epigenetic regulation of protein tyrosine phosphatases: potential molecular targets for cancer therapy" Cancer Gene Ther 8:665-72.

Bai S, Ghoshal K, Datta J, Majumder S, Yoon SO and Jacob ST (2005) "DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2" Mol Cell Biol 2:751-66.

Motiwala T, Kutay H, Ghoshal K, Bai S, Seimiya H, Tsuruo T, Suster S, Morrison C and Jacob ST (2004) "Protein tyrosine phosphatase receptor-type O (PTPRO) exhibits characteristics of a candidate tumor suppressor in human lung cancer" Proc Natl Acad Sci USA 38:13844-9.

Majumder S, Varadharaj S, Ghoshal K, Monani U, Burghes AH and Jacob ST (2004) "Identification of a novel cyclic AMP-response element (CRE-II) and the role of CREB-1 in the cAMP-induced expression of the survival motor neuron (SMN) gene" J Biol Chem 15:14803-11.

Ghoshal K, Majumder S, Datta J, Motiwala T, Bai S, Sharma SM, Frankel W and Jacob ST (2003) "Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression" J Biol Chem 8:6783-93.

Motiwala T, Ghoshal K, Das A, Majumder S, Weichenhan D, Wu YZ, Holman K, James SJ, Jacob ST and Plass C (2003) "Suppression of the protein tyrosine phosphatase receptor type O gene (PTPRO) by methylation in hepatocellular carcinomas" Oncogene 41:6319-31.

Majumder S, Ghoshal K, Summers D, Bai S, Datta J and Jacob ST (2003) "Chromium(VI) down-regulates heavy metal-induced metallothionein gene transcription by modifying transactivation potential of the key transcription factor, metal-responsive transcription factor 1" J Biol Chem 28:26216-26.

Dong X, Ghoshal K, Majumder S, Yadav P and Jacob ST (2002) "Mitochondrial transcription factor A and its downstream targets are unregulated in a rat hepatoma" J Biol Chem 277:43309-18.

Ghoshal K, Datta J, Majumder S, Dong X, Parthun M and Jacob ST (2002) "Inhibitors of histone deacetylase and DNA methyltransferase synergistically activate the methylated metallothionein I promoter by activating the transcription factor MTF-1 and forming an open chromatin structure" Mol Cell Biol 22:8302-19.