Contributions to Science

Description

Functional characterization of candidate oncogenes and tumor suppressor genes: During graduate studies, my research focused on functional characterization of calcitonin-related peptide in normal physiology of reproduction and pathophysiology of prostate cancer progression. My contribution to this field included the cloning and characterization of the expression of calcitonin-related peptide and the signaling pathway mediated through Gs and Gq G-proteins. My postdoctoral studies focused on functional characterization of candidate tumor suppressor genes in ovarian cancer. My contribution to this field includes cloning and characterization of the functions of three candidate tumor suppressor genes: TCEAL7, SULF1, and HTRA1.

Citations

  1. Chien J, Narita K, Rattan R, Giri S, Shridhar R, Staub J, Beleford D, Lai J, Roberts LR, Molina J, Kaufmann SH, Prendergast GC, Shridhar V. A role for candidate tumor-suppressor gene TCEAL7 in the regulation of c-Myc activity, cyclin D1 levels and cellular transformation. Oncogene. 2008 Dec 11;27(58):7223-34. PubMed PMID: 18806825; NIHMSID: NIHMS121795; PubMed Central PMCID: PMC2754286.
  2. Chien J, Staub J, Hu SI, Erickson-Johnson MR, Couch FJ, Smith DI, Crowl RM, Kaufmann SH, Shridhar V. A candidate tumor suppressor HtrA1 is downregulated in ovarian cancer. Oncogene. 2004 Feb 26;23(8):1636-44. PubMed PMID: 14716297.
  3. Lai JP, Chien J, Strome SE, Staub J, Montoya DP, Greene EL, Smith DI, Roberts LR, Shridhar V. HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck squamous carcinoma. Oncogene. 2004 Feb 19;23(7):1439-47. PubMed PMID: 14973553.
  4. Chien J, Wong E, Nikes E, Noble MJ, Pantazis CG, Shah GV. Constitutive activation of stimulatory guanine nucleotide binding protein (G(S)alphaQL)-mediated signaling increases invasiveness and tumorigenicity of PC-3M prostate cancer cells. Oncogene. 1999 Jun 3;18(22):3376-82. PubMed PMID: 10362358.

Description

Genetics and epigenetics of ovarian cancer: As an independent investigator, my research focuses on understanding the genetics of ovarian cancer, and my contribution to this field includes expression analysis of early-stage ovarian cancer, integrated analysis of ovarian cancer genomes through TCGA Research Network, and development of methods and analysis tools through collaborations with other investigators.

Citations

  1. Kommoss S, Winterhoff B, Oberg AL, Konecny GE, Wang C, Riska SM, Fan JB, Maurer MJ, April C, Shridhar V, Kommoss F, du Bois A, Hilpert F, Mahner S, Baumann K, Schroeder W, Burges A, Canzler U, Chien J, Embleton AC, Parmar M, Kaplan R, Perren T, Hartmann LC, Goode EL, Dowdy SC, Pfisterer J. Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes. Clin Cancer Res. 2017 Jul 15;23(14):3794-3801. PubMed PMID: 28159814; NIHMSID: NIHMS910056; PubMed Central PMCID: PMC5661884.
  2. Chien J, Ota T, Aletti G, Shridhar R, Boccellino M, Quagliuolo L, Baldi A, Shridhar V. Serine protease HtrA1 associates with microtubules and inhibits cell migration. Mol Cell Biol. 2009 Aug;29(15):4177-87. PubMed PMID: 19470753; PubMed Central PMCID: PMC2715801.
  3. Staub J, Chien J, Pan Y, Qian X, Narita K, Aletti G, Scheerer M, Roberts LR, Molina J, Shridhar V. Epigenetic silencing of HSulf-1 in ovarian cancer:implications in chemoresistance. Oncogene. 2007 Jul 26;26(34):4969-78. PubMed PMID: 17310998.
  4. Chien J, Staub J, Avula R, Zhang H, Liu W, Hartmann LC, Kaufmann SH, Smith DI, Shridhar V. Epigenetic silencing of TCEAL7 (Bex4) in ovarian cancer. Oncogene. 2005 Jul 28;24(32):5089-100. PubMed PMID: 15870691.

Description

Molecular cancer therapeutics: My contribution to this field includes identification of HTRA1, FOXM1, and VCP as therapeutic targets in ovarian cancer. We have shown that HTRA1 is induced by chemotherapy, leading to its limited proteolysis and the activation of protease activity. Active HTRA1 contributes to caspase activation and apoptosis. Our studies show that FOXM1 expression is upregulated in ovarian cancer and that this upregulation is due to loss of negative regulation by p53. We show that p53-FOXM1 axis can be targeted by FOXM1 inhibitor thiostrepton and it enhances sensitivity to cisplatin. Finally, our recent studies show that VCP inhibition results in ER stress, unfolded protein response, and apoptosis.

Citations

  1. Bastola P, Neums L, Schoenen FJ, Chien J. VCP inhibitors induce endoplasmic reticulum stress, cause cell cycle arrest, trigger caspase-mediated cell death and synergistically kill ovarian cancer cells in combination with Salubrinal. Mol Oncol. 2016 Dec;10(10):1559-1574. PubMed PMID: 27729194; PubMed Central PMCID: PMC5423134.
  2. Zhang L, Hapon MB, Goyeneche AA, Srinivasan R, Gamarra-Luques CD, Callegari EA, Drappeau DD, Terpstra EJ, Pan B, Knapp JR, Chien J, Wang X, Eyster KM, Telleria CM. Mifepristone increases mRNA translation rate, triggers the unfolded protein response, increases autophagic flux, and kills ovarian cancer cells in combination with proteasome or lysosome inhibitors. Mol Oncol. 2016 Aug;10(7):1099-117. PubMed PMID: 27233943; NIHMSID: NIHMS786650; PubMed Central PMCID: PMC5240778.
  3. He X, Khurana A, Maguire JL, Chien J, Shridhar V. HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation. Int J Cancer. 2012 Mar 1;130(5):1029-35. PubMed PMID: 21387310; NIHMSID: NIHMS303569; PubMed Central PMCID: PMC3206182.
  4. Chien J, Aletti G, Baldi A, Catalano V, Muretto P, Keeney GL, Kalli KR, Staub J, Ehrmann M, Cliby WA, Lee YK, Bible KC, Hartmann LC, Kaufmann SH, Shridhar V. Serine protease HtrA1 modulates chemotherapy-induced cytotoxicity. J Clin Invest. 2006 Jul;116(7):1994-2004. PubMed PMID: 16767218; PubMed Central PMCID: PMC1474818.

Description

Bioinformatics and Genomics: My contribution to this field includes development of methods to analyze next-generation sequencing data to gain biological insights from large genomic data sets.

Citations

  1. Meier R, Graw S, Beyerlein P, Koestler D, Molina JR, Chien J. digit-a tool for detection and identification of genomic interchromosomal translocations. Nucleic Acids Res. 2017 May 19;45(9):e72. PubMed PMID: 28132028; PubMed Central PMCID: PMC5435966.
  2. Belinsky MG, Rink L, Cai KQ, Capuzzi SJ, Hoang Y, Chien J, Godwin AK, von Mehren M. Somatic loss of function mutations in neurofibromin 1 and MYC associated factor X genes identified by exome-wide sequencing in a wild-type GIST case. BMC Cancer. 2015 Nov 10;15:887. PubMed PMID: 26555092; PubMed Central PMCID: PMC4641358.
  3. Munchel S, Hoang Y, Zhao Y, Cottrell J, Klotzle B, Godwin AK, Koestler D, Beyerlein P, Fan JB, Bibikova M, Chien J. Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics. Oncotarget. 2015 Sep 22;6(28):25943-61. PubMed PMID: 26305677; PubMed Central PMCID: PMC4694877.
  4. Graw S, Meier R, Minn K, Bloomer C, Godwin AK, Fridley B, Vlad A, Beyerlein P, Chien J. Robust gene expression and mutation analyses of RNA-sequencing of formalin-fixed diagnostic tumor samples. Sci Rep. 2015 Jul 23;5:12335. PubMed PMID: 26202458; PubMed Central PMCID: PMC4511951.

Complete list of publications:
PubMed NCBI Collection