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.


Research Focus

Cancer Genomics, Cancer Therapeutics, Translational Genomics, Ovarian Cancer

Applied Genomics & Cancer Therapeutics (AGCT) Program website

Research Description

The primary objective of my research program is to understand the genetic basis of ovarian cancer and to translate this knowledge into clinical applications in the early detection and the treatment of ovarian cancer. To support this objective, my current research focuses on three areas:

  • Genomics of ovarian cancer: Although genetic alterations are considered as a hallmark of cancer, specific genetic alterations serve as "drivers" in cancer progression while others are considered "passenger" mutations.  Advances in the identification of "driver" genetic alterations in cancer will lead to the development of novel therapeutic targets to effectively treat cancer, and it is a prerequisite in the era of "Personalized Medicine" or "Precision Cancer Medicine." My research focuses on the characterization of genetic mutations from cancer genomes to identify driver mutations in ovarian cancer.  I apply various approaches in functional genetics, genomics, and bioinformatics to identify somatic mutations (single nucleotide variants, insertions and deletions, translations, fusion transcripts, copy number alterations) and aberrantly expressed genes (that are associated with clinical outcomes) to elucidate the genetic basis of ovarian cancer. 
  • Development of genome-based biomarkers for early detection of ovarian cancer. Recent studies by the Cancer Genome Atlas identifies TP53 mutations in 95% of high-grade serous ovarian cancer.  Almost universal nature of TP53 mutations in this disease inspires us to test whether these mutations serve as biomarkers for diagnosis and detection of high-grade serous ovarian cancer.  We are applying emerging PCR methods and next-generation sequencing technologies to identify low-level TP53 mutations in patient samples so that these genomics assays may later be translated as clinical assays in the diagnosis of early-stage ovarian cancer.  
  • Development of targeted therapies for advanced-stage ovarian cancer. The Cancer Genome Atlas studies also identifies FoxM1 as a candidate gene that is overexpressed in 84% of high-grade serous ovarian cancer.  High levels of FoxM1 expression in this disease suggest it may serve as a therapeutic target, analogous to Her2 in breast cancer, Abl in leukemia, and Braf in melanoma serving as therapeutic targets in respective diseases.  We are evaluating two antibiotics and an experimental therapeutic agent to characterize their cytotoxic activity in ovarian cancer cells and to understand how these agents are affecting FoxM1 expression and inducing cytotoxic effects in cancer cells. Ultimately, we plan to exploit genetic vulnerabilties in ovarian cancer by identifying synthetic lethal interactions and by developing therapeutic combinations that cause synthetic lethality in ovarian cancer

Lab Members

Postdoctoral Fellows

Ying Wan

Megan Cooley, PhD 

Postdoctoral Fellow
2014 K-INBRE Fellow

Jill Madden, PhD

Postdoctoral Fellow

Ying Wan, PhD

Postdoctoral Fellow

Yanchun Guo, PhD

Postdoctoral Fellow

 

Students

Stefan Kay Pingping

Richard Meier, BS 

MS in Bioinformatics

Stefan Graw, BS       

MS in Bioinformatics

Kay Minn, BS

MS in Pathology            

Pingping Fang, MS

IGPBS PhD student

       
Bernard Younshim Park    

Bernard Herrman, BS

MS in Molecular Biotechnology

Younshim Park, MS

IGPBS PhD student (Summer rotation)

   

Technician

Lynn      

Lynn Magenheimer, MS

Research Assistant

     

Publications:

  1. Chen Wang, Mine S Cicek, Bridget Charbonneau, Kimberly R Kalli, Sebastian M Armasu, Melissa C Larson, Gottfried E Konecny, Boris Winterhoff, Jian-Bing Fan, Marina Bibikova, Jeremy Chien, Viji Shridhar, Matthew S Block, Lynn C Hartmann, Daniel W Visscher, Julie M Cunningham, Keith L Knutson, Brooke L Fridley, Ellen L Goode. Tumor Hypomethylation at 6p21.3 Associates with Longer Time to Recurrence of High-Grade Serous Epithelial Ovarian Cancer. Cancer Research. 04/2014; DOI:10.1158/0008-5472.CAN-13-3198.
  2. Chien J*, Kuang R, Landen C, Shridhar V*. Platinum-sensitive Recurrence in Ovarian Cancer: The Role of Tumor Microenvironment. Frontiers in Oncology, 2013 Sep 24; 3:251 *co-corresponding authors
  3. He X, Chien J, Shridhar V.  Assessment of resistance to anoikis in ovarian cancer. Methods in Molecular Biology. 2013; 1049:347-54.
  4. Brandon Leonard, Steven N. Hart, Michael B. Burns, Michael A. Carpenter, Nuri A. Temiz, Anurag Rathore, Rachel Isaksson Vogel, Jason B. Nikas, Emily K. Law, William L. Brown, Ying Li, Yuji Zhang, Matthew J. Maurer, Ann L. Oberg, Julie M. Cunningham, Viji Shridhar, Debra A. Bell, Craig April, David Bentley, Marina Bibikova, R. Keira Cheetham, Jian-Bing Fan, Russell Grocock, Sean Humphray, Zoya Kingsbury, John Peden, Jeremy Chien, Elizabeth M. Swisher, Lynn C. Hartmann, Kimberly R. Kalli, Ellen L. Goode, Hugues Sicotte, Scott H. Kaufmann, and Reuben S. Harris.  APOBEC3B upregulation and genomic mutation patterns in serous ovarian carcinoma.  Cancer Research. 2013. (accepted on October 18, 2013).
  5. Chien J. Functional Cancer Genomics: A Way to Bridge the Gap between Genomic Information and Biological Knowledge. Journal of Cancer Biology & Research. 2013. 1:4.
  6. Julie Cunningham, Mine Cicek, Nicholas Larson, Jaime Davila, Chen Wang, Melissa Larson, Honglin Son, Ed Dicks, Patricia Harrington, Myra Wick, Boris Winterhoff, Habib Hamidi, Gottfried Konecny, Jeremy Chien, Marina Bibikova, Jian-Bing Fan, Kimberly Kalli, Noralene Lindor, Brooke Fridley, Paul Pharoah, and Ellen Goode. Clinical Characteristics of Ovarian Cancer Classified by BRCA1, BRCA2, and RAD51C Status. Scientific Report (accepted on January 20, 2014).
  7. Devin C Koestler, Prabhakar Chalise, Mine S Cicek, Julie M Cunningham, Sebastian Armasu, Melissa C Larson, Jeremy Chien, Matthew Block, Kimberly R Kalli, Thomas A Sellers, Brooke L Fridley, Ellen L Goode. Integrative genomic analysis identifies epigenetic marks that mediate genetic risk for epithelial ovarian cancer. BMC Medical Genomics. 01/2014; 7(1):8. DOI:10.1186/1755-8794-7-8
  8. Kumar S, Meuter A, Thapa P, Langstraat C, Giri S, Chien J, Rattan R, Cliby W, Shridhar V. Metformin intake is associated with better survival in ovarian cancer: A case-control study. Cancer. 2013 Feb 1; 119(3):555-62. View PubMed
  9. He X, Chien J, Shridhar V.  Assessment of resistance to anoikis in ovarian cancer. Methods in Molecular Biology. 2013; 1049:347-54.
  10. Beleford D, Chien J*, Shridhar V*. HtrA1 Peptidase.  Handbook of Proteolytic Enzymes (Third Edition). Edited by Neil D. Rawlings and Guy Salvesen. 2013. *Co-corresponding authors
  11. Khuarana A, Beleford D, He X, Chien J, Shridhar V. Role of heparan sulfatases in ovarian and breast cancer. Am J Cancer Res. 2013:3(1). View PubMed
  12. Zhang W, Ota T, Shridhar V, Chien J, Wu B, Kuang R. Network-based survival analysis reveals subnetwork signatures for predicting outcomes of ovarian cancer treatment. PLoS Computational Biology. View PubMed
  13. Cicek MS, Koestler DC, Fridley BL, Kalli KR, Armasu SM, Larson MC, Wang C, Winham SJ, Vierkant RA, Rider DN, Block MS, Klotzle B, Konecny G, Winterhoff BJ, Hamidi H, Shridhar V, Fan JB, Visscher DW, Olson JE, Hartmann LC, Bibikova M, Chien J, Cunningham JM, Goode EL. Epigenome-wide Ovarian Cancer Analysis Identifies a Methylation Profile Differentiating Clear Cell Histology with Epigenetic Silencing of HERG K+ Channel. Human Mol Genetic. 2013 April 9. View PubMed
  14. 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. View PubMed
  15. 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. View PubMed
  16. 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.
    View PubMed
  17. 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. View PubMed
  18. 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. View PubMed
  19. 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. View PubMed
  20. 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. View PubMed
  21. 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. View PubMed
  22. 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. View PubMed
  23. 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.
    View PubMed
  24. 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.
    View PubMed
  25. 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.
    View PubMed
  26. 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.
    View PubMed
  27. 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.
    View PubMed
  28. 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.
    View PubMed
  29. 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.
    View PubMed
  30. 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.
    View PubMed
  31. 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.
    View PubMed
  32. 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.
    View PubMed
  33. 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.
    View PubMed
  34. 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.
    View PubMed
  35. 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.
    View PubMed
  36. 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.
    View PubMed
  37. 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.
    View PubMed
  38. 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.
    View PubMed
  39. 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.
    View PubMed
  40. 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.
    View PubMed
  41. 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.
    View PubMed
  42. 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.
    View PubMed
  43. 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.
    View PubMed
  44. 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.
    View PubMed
  45. 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.
    View PubMed
  46. 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.
    View PubMed
  47. 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.
    View PubMed
  48. 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.
    View PubMed
  49. 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.
    View PubMed
  50. 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.
    View PubMed
  51. 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.
    View PubMed
  52. 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.
    View PubMed
  53. 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.  View PubMed
Last modified: Jul 15, 2014

Jeremy Chien, PhD

Contact

Jeremy Chien, PhD
Assistant Professor, Cancer Biology
Assistant Director, Translational Genomics, University of Kansas Cancer Center

2020B Wahl Hall East, Mailstop 1027
3901 Rainbow Boulevard
Kansas City, KS 66160

P: 913-945-8082
jchien@kumc.edu

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