Jeremy Chien, PhD

Assistant Professor, Cancer Biology
Assistant Director, Translational Genomics, University of Kansas Cancer Center
Ph.D.: Reproductive Physiology, University of Kansas Medical Center, Kansas City, Kan.
Postdoctoral: Tumor Biology, Mayo Clinic, Rochester, Minn.

Integrated Cancer Genomics Lab website

Research Description

The primary goal of my research program is to understand the genetic basis for ovarian carcinogenesis. To achieve this goal, I use two complementary genetic and functional approaches: the genetic approaches are used to identify candidate disease genes by next-generation sequencing of cancer genomes; and the functional approaches are used to characterize molecular mechanisms of candidate disease genes in ovarian carcinogenesis. My long-term goals are to advance ovarian cancer biology through integrated cancer genomics, functional genomics, and proteomics, and to translate these advances into clinical applications in early detection, diagnosis, prognosis, and treatment of ovarian cancer.

I am applying next-generation sequencing technologies, functional genomics, and proteomics to characterize alterations in cancer genomes and biological pathways associated with critical steps in ovarian carcinogenesis; namely, malignant transformation, metastasis, and resistance to chemotherapy. Using mouse models, I am defining the in vivo role of tumor suppressor genes and oncogenes in tubal carcinogenesis. In addition, I am applying next generation sequencing technologies to develop genome-based biomarkers for the detection and diagnosis of ovarian cancer. Ultimately, I plan to employ various expertise acquired through previous training in reproductive physiology, cancer genetics, and tumor biology to integrate system-level understanding with molecular-level approaches to understand ovarian carcinogenesis.

Lab Members

Kay Minn Laboratory Manager	Xuan (Jessie) Zhang Senior Scientist	Yen Haong Research Assisant	Magdalena Waggoner Student

Publications:

1. 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. Epub 2011 Apr 25.
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2. Fan JB, Chen J, April CS, Fisher JS, Klotzle B, Bibikova M, Kaper F, Ronaghi M, Linnarsson S, Ota T, Chien J, Laurent LC, Nisperos SV, Chen GY, Zhong JF. Highly parallel genome-wide expression analysis of single mammalian cells. PLoS ONE. 2012; 7(2):e30794.
3. Goode EL, Chenevix-Trench G, Hartmann LC, Fridley BL, Kalli KR, Vierkant RA, Larson MC, White KL, Keeney GL, Oberg TN, Cunningham JM, Beesley J, Johnatty SE, Chen X, Goodman KE, Armasu SM, Rider DN, Sicotte H, Schmidt MM, Elliott EA, Hogdall E, Kjaer SK, Assessment of hepatocyte growth factor in ovarian cancer mortality. Cancer Epidemiol Biomarkers Prev. 2011 Aug; 20(8):1638-48. Epub 2011 Jul 01.
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4. Li Y, Chien J, Smith DI, Ma J. FusionHunter: identifying fusion transcripts in cancer using paired-end RNA-seq. Bioinformatics. 2011 Jun 15; 27(12):1708-10. Epub 2011 May 05.
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5. Khurana A, Liu P, Mellone P, Lorenzon L, Vincenzi B, Datta K, Yang B, Linhardt RJ, Lingle W, Chien J, Baldi A, Shridhar V. HSulf-1 modulates FGF2- and hypoxia-mediated migration and invasion of breast cancer cells. Cancer Res. 2011 Mar 15; 71(6):2152-61. Epub 2011 Jan 25.
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6. Mullany SA, Moslemi-Kebria M, Rattan R, Khurana A, Clayton A, Ota T, Mariani A, Podratz KC, Chien J, Shridhar V. Expression and functional significance of HtrA1 loss in endometrial cancer. Clin Cancer Res. 2011 Feb 1; 17(3):427-36. Epub 2010 Nov 23.
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7. Ota T, Clayton AC, Minot DM, Shridhar V, Hartmann LC, Gilks CB, Chien JR. Minichromosome maintenance protein 7 as a potential prognostic factor for progression-free survival in high-grade serous carcinomas of the ovary. Mod Pathol. 2011 Feb; 24(2):277-87. Epub 2010 Nov 12.
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8. Gonzalez Bosquet J, Peedicayil A, Maguire J, Chien J, Rodriguez GC, Whitaker R, Petitte JN, Anderson KE, Barnes HJ, Shridhar V, Cliby WA. Comparison of gene expression patterns between avian and human ovarian cancers. Gynecol Oncol. 2011 Feb; 120(2):256-64. Epub 2010 Nov 19.
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9. Chien J. WT1 as a substrate of HtrA2: a potential pathway for therapeutic targeting by HtrA proteases. Future Oncol. 2010 Aug; 6(8):1233-5.
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10. Beleford D, Rattan R, Chien J, Shridhar V. High temperature requirement A3 (HtrA3) promotes etoposide- and cisplatin-induced cytotoxicity in lung cancer cell lines. J Biol Chem. 2010 Apr 16; 285(16):12011-27. Epub 2010 Feb 12.
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11. He X, Ota T, Liu P, Su C, Chien J, Shridhar V. Downregulation of HtrA1 promotes resistance to anoikis and peritoneal dissemination of ovarian cancer cells. Cancer Res. 2010 Apr 15; 70(8):3109-18. Epub 2010 Apr 13.
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12. Rattan R, Narita K, Chien J, Maguire JL, Shridhar R, Giri S, Shridhar V. TCEAL7, a putative tumor suppressor gene, negatively regulates NF-kappaB pathway. Oncogene. 2010 Mar 4; 29(9):1362-73. Epub 2009 Dec 07.
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13. 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. Epub 2009 May 26.
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14. Chien J, Fan JB, Bell DA, April C, Klotzle B, Ota T, Lingle WL, Gonzalez Bosquet J, Shridhar V, Hartmann LC. Analysis of gene expression in stage I serous tumors identifies critical pathways altered in ovarian cancer. Gynecol Oncol. 2009 Jul; 114(1):3-11. Epub 2009 May 01.
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15. Chien J, Campioni M, Shridhar V, Baldi A. HtrA serine proteases as potential therapeutic targets in cancer. Curr Cancer Drug Targets. 2009 Jun; 9(4):451-68.
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16. Chien J, He X, Shridhar V. Identification of tubulins as substrates of serine protease HtrA1 by mixture-based oriented peptide library screening. J Cell Biochem. 2009 May 15; 107(2):253-63.
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17. 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. Epub 2008 Sep 22.
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18. Ajayi F, Kongoasa N, Gaffey T, Asmann YW, Watson WJ, Baldi A, Lala P, Shridhar V, Brost B, Chien J. Elevated expression of serine protease HtrA1 in preeclampsia and its role in trophoblast cell migration and invasion. Am J Obstet Gynecol. 2008 Nov; 199(5):557.e1-10. Epub 2008 Jul 29.
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19. Yang Z, Chen Y, Lillo C, Chien J, Yu Z, Michaelides M, Klein M, Howes KA, Li Y, Kaminoh Y, Chen H, Zhao C, Chen Y, Al-Sheikh YT, Karan G, Corbeil D, Escher P, Kamaya S, Li C, Johnson S, Frederick JM, Zhao Y, Wang C, Cameron DJ, Huttner WB, Schorderet DF, Mutant prominin 1 found in patients with macular degeneration disrupts photoreceptor disk morphogenesis in mice. J Clin Invest. 2008 Aug; 118(8):2908-16.
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20. Baldi A, Mottolese M, Vincenzi B, Campioni M, Mellone P, Di Marino M, di Crescenzo VG, Visca P, Menegozzo S, Spugnini EP, Citro G, Ceribelli A, Mirri A, Chien J, Shridhar V, Ehrmann M, Santini M, Facciolo F. The serine protease HtrA1 is a novel prognostic factor for human mesothelioma. Pharmacogenomics. 2008 Aug; 9(8):1069-77.
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21. Chien JR, Aletti G, Bell DA, Keeney GL, Shridhar V, Hartmann LC. Molecular pathogenesis and therapeutic targets in epithelial ovarian cancer. J Cell Biochem. 2007 Dec 1; 102(5):1117-29.
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22. 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. Epub 2007 Feb 19.
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23. Narita K, Chien J, Mullany SA, Staub J, Qian X, Lingle WL, Shridhar V. Loss of HSulf-1 expression enhances autocrine signaling mediated by amphiregulin in breast cancer. J Biol Chem. 2007 May 11; 282(19):14413-20. Epub 2007 Mar 15.
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24. Yang Z, Camp NJ, Sun H, Tong Z, Gibbs D, Cameron DJ, Chen H, Zhao Y, Pearson E, Li X, Chien J, Dewan A, Harmon J, Bernstein PS, Shridhar V, Zabriskie NA, Hoh J, Howes K, Zhang K. A variant of the HTRA1 gene increases susceptibility to age-related macular degeneration. Science. 2006 Nov 10; 314(5801):992-3. Epub 2006 Oct 19.
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25. Spugnini EP, Cardillo I, Verdina A, Crispi S, Saviozzi S, Calogero R, Nebbioso A, Altucci L, Cortese G, Galati R, Chien J, Shridhar V, Vincenzi B, Citro G, Cognetti F, Sacchi A, Baldi A. Piroxicam and cisplatin in a mouse model of peritoneal mesothelioma. Clin Cancer Res. 2006 Oct 15; 12(20 Pt 1):6133-43.
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26. Wang X, Zheng L, Zeng Z, Zhou G, Chien J, Qian C, Vasmatzis G, Shridhar V, Chen L, Liu W. DIXDC1 isoform, l-DIXDC1, is a novel filamentous actin-binding protein. Biochem Biophys Res Commun. 2006 Aug 18; 347(1):22-30. Epub 2006 Jun 19.
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27. 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. Epub 2006 Jun 08.
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28. Narita K, Staub J, Chien J, Meyer K, Bauer M, Friedl A, Ramakrishnan S, Shridhar V. HSulf-1 inhibits angiogenesis and tumorigenesis in vivo. Cancer Res. 2006 Jun 15; 66(12):6025-32.
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29. Lewis KA, Mullany S, Thomas B, Chien J, Loewen R, Shridhar V, Cliby WA. Heterozygous ATR mutations in mismatch repair-deficient cancer cells have functional significance. Cancer Res. 2005 Aug 15; 65(16):7091-5.
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30. 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.
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31. 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.
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32. 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.
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33. Lai JP, Chien JR, Moser DR, Staub JK, Aderca I, Montoya DP, Matthews TA, Nagorney DM, Cunningham JM, Smith DI, Greene EL, Shridhar V, Roberts LR. hSulf1 Sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling. Gastroenterology. 2004 Jan; 126(1):231-48.
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34. Lai J, Chien J, Staub J, Avula R, Greene EL, Matthews TA, Smith DI, Kaufmann SH, Roberts LR, Shridhar V. Loss of HSulf-1 up-regulates heparin-binding growth factor signaling in cancer. J Biol Chem. 2003 Jun 20; 278(25):23107-17. Epub 2003 Apr 09.
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35. Shridhar V, Sen A, Chien J, Staub J, Avula R, Kovats S, Lee J, Lillie J, Smith DI. Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization. Cancer Res. 2002 Jan 1; 62(1):262-70.
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36. Ren Y, Chien J, Sun YP, Shah GV. Calcitonin is expressed in gonadotropes of the anterior pituitary gland: its possible role in paracrine regulation of lactotrope function. J Endocrinol. 2001 Nov; 171(2):217-28.
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37. Chien J, Ren Y, Qing Wang Y, Bordelon W, Thompson E, Davis R, Rayford W, Shah G. Calcitonin is a prostate epithelium-derived growth stimulatory peptide. Mol Cell Endocrinol. 2001 Jul 5; 181(1-2):69-79.
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38. Chien J, Shah GV. Role of stimulatory guanine nucleotide binding protein (GSalpha) in proliferation of PC-3M prostate cancer cells. Int J Cancer. 2001 Jan 1; 91(1):46-54.
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39. Shah GV, Chien J, Sun YP, Puri S, Ravindra R. Calcitonin inhibits anterior pituitary cell proliferation in the adult female rats. Endocrinology. 1999 Sep; 140(9):4281-91.
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40. 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 Jun 3; 1999; 18(22):3376-82.