Kenneth P. Nephew, Ph.D.

Professor Cellular and Integrative Physiology and Obstetrics and Gynecology

My research interests are focused in the following areas:

  • Cancer epigenetics (DNA methylation and histone modifications)
  • Nuclear receptors and steroid hormone action
  • Translational research in female malignancies (ovarian cancer, breast cancer)
  • Cancer biomarkers

Active research projects ongoing in my lab are focused on cancer epigenetics, cancer stem cells, cancer biomarkers, and estrogen receptor biology. Graduate students, post doctoral fellow, research technicians, undergraduates, and senior research scientists (PhD level) are actively working in my laboratory on all of these important areas of cancer.


We have recently isolated and characterized human ovarian cancer initiating cells (also known as cancer stem cells) and have begun a comprehensive assessment of ovarian cancer stem/progenitor cell epigenetics. Our goal is to target the biologic pathways critical to ovarian tumor initiating cells. In addition, DNA methylation biomarkers may represent a promising approach for the assessment and management of ovarian cancer, an avenue of research my laboratory is currently pursuing in an ovarian cancer clinical trial.


Towards the understanding of cancer as a complex biological and biochemical system, we are using experimental and computational approaches to gain new insights into the development and progression of cancer through a systems-wide approach. Our Center for Integrative Cancer Biology is collaborating with colleagues at the Ohio State University. This integrative and multi-disciplinary effort incorporates a spectrum of new technologies, such as epigenomics and methylation microarrays, to generate computer and mathematical models that may predict cancer epigenetic processes.


We are investigating the antiproliferative effects of endocrine therapies on breast cancer cells. Many patients who initially respond to these therapies ultimately relapse, having acquired resistance. Unfortunately, resistance can lead to aggressive disease progression and metastasis, conferring poorer patient outlook. Thus, acquired resistance constitutes a significant clinical problem with all treatment approaches examined to date. To better understand acquired resistance and develop additional therapeutic strategies for the management of breast cancer, my laboratory has developed novel breast cancer cell culture models representing acquired resistance to tamoxifen, fulvestrant and aromatase inhibitors. These pre-clinical models representing breast cancer cells able to harness distinctly dissimilar pathways in response to the anti-hormone strategies currently in clinical use are a focus of my current and future breast cancer studies.

Kenneth P. Nephew Research Lab 

Further information about my research and teaching interests may be found in my CV.



Give to The Ovarian Cancer Research Fund

Publications (Selected)

  • Lengyel E, Burdette J, Kenny H, Matei D, Pilrose J,  Nephew KP, Hale B, Stack MS. Epithelial ovarian cancer experimental models.  Oncogene, in press
  • Hsu PY, Hsu HK, Lan X,  Yan PS, Labanowska J, Heerema N, Hsiao TZ, Chiu YC,  Liu Y,  Li L, Nephew KP, Thompson IM, Li R, Sharp ZD, Chen Y,Kirma NB, Jin VX, Huang THM  Amplification of distant estrogen response elements (DERE) amplification drives breast cancer progression and tamoxifen resistance.  Cancer Cell, in press
  • Huang RL, Gu F, Kirma NB,  Ruan J, Chen CL, Wang HC,  Liao YP, Chang CC,  Yu MH, Thompson IM, Huang HC, Huang TMH, Lai HC,  Nephew KP.  Comprehensive methylome analysis of ovarian tumors reveals hedgehog signaling pathway regulators as prognostic DNA methylation biomarkers.  Epigenetics, in press
  • Miller FD, Yan PS, Buechlein A, Rodriguez BA, Yilmaz AS; Goel S; Lin H, Bridgette Collins-Burow B, Rhodes LV, Braun C; Pradeep S, Rupaimoole R, Dalkilic M, Sood AK; Burow ME, Tang H, Huang TH,  Liu Y, Rusch DB, Nephew KP.  A new method for stranded whole transcriptome RNA-seq, Methods, in press
  • Rao X, Evans J, Chae H, Kim S, Yan P, Liu Y, Pilrose J, Miller D, Rhee J-K, Huang Y-W, Gu F,  Gray JW, Huang TH-M, Nephew KP. CpG island shore methylation regulates caveolin-1 in breast cancer  Oncogene, in press
  • Matei D, Fang F, Shen C, Schilder J, Arnold A, Zeng Y, Berry WA, Huang TH, Nephew KP. 2012 Epigenetic resensitization to platinum in ovarian cancer Cancer Res, 72:2197-2205 PMID: 22549947
  • Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR 2011  Rethinking ovarian cancer: recommendations for improving outcomes.  Nat Rev Cancer 11:719-25 PMC3380637
  • Rao X Di Leva G Li M, Fang F, Hartman-Frey C, Burow  ME,  Croce C,  Nephew KP. 2011  MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways.  Oncogene,30:1082-97 PMC3342929
  • Fang F, Balch C, Schilder S, Breen T, Zhang S, Shen C, Li L, Kulesavage C, Snyder AJ, Nephew KP*, Matei DE*.  2010  A phase I and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer. Cancer, 116:4043-53 (*corresponding authors) PMC2930033
  • Hsu P-Y, Hsu H-K, Singer GAC, Yan PS, Rodriguez BAT, Liu JC, Weng YI, Deatherage DE, Chen Z, Pereira JS, Lopez R, Russo J, Wang Q, Lamartiniere CA, Nephew KP, Huang TH-M. 2010 Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping.  Genome Res, 20:733-44 PMC2877570
  • Matei DE*, Nephew KP*.  2010 Epigenetic therapies for chemosensitization of epithelial ovarian cancer. Gynecol Oncol  116:195-201
  • Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS,  Huang THM,  Nephew KP.  2008 Identification and characterization of ovarian cancer-initiating cells from primary human tumors.   Cancer Res 68:4311-4320 (cover article) PMC2553722
  • Fan M, Rickert EL, Chen L, Aftab SA, Nephew KP, Weatherman R. 2007 Characterization of molecular and structural determinants of selective estrogen receptor downregulators. Breast Cancer Res Treat 103:37–44
  • Fan M, Yan PS,  Hartman-Frey C, Chen L,  Paik H, Abbosh PH, Cheng ASL, Li L, Huang T H-M, Nephew KP. 2006 Diverse gene expression and DNA methylation profiles correlate with differential adaptation of breast cancer cells to the antiestrogens tamoxifen and fulvestrant. Cancer Res 66:11954-66
  • Abbosh PH, Montgomery JS, Starkey JA, Novotny M, Zuhowski EG, Egorin MJ, Park AK, Golas A, Brannon KM, Balch C, Huang TH-M, Nephew KP.  2006 Dominant-negative histone H3 lysine 27 mutant derepresses silenced tumor suppressor genes and reverses the drug-resistant phenotype in cancer cells. Cancer Res 66: 5582-5591
  • Wei SH, Paik HH, Balch C, Kim YS, Baldwin RL, Liyanarachchi S, Li L, Wang Z, Wan JC, Davuluri RV, Karlan BY,  Brown R, Kim S, Huang THM, Nephew KP.  2006 DNA biomarkers possessing methylation-predictive sequence patterns in ovarian cancer. Clin Cancer Res 12:2788-94
  • Long X, Nephew KP.  2006 Fulvestrant (ICI 182,780)-dependent interacting proteins mediate immobilization and degradation of estrogen receptor-a. J Biol Chem, 281:9607-15
  • Cheng ASL, Jin VX, Yan PS, Fan M, Leu YW, Chan MWY, Plass C, Nephew KP, Davuluri RV, Huang TH-M. 2006 Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-a responsive promoters.  Molecular Cell 3:393-404
  • Leu YW, Yan PS, Fan W, Jin VX, Liu CJ, Curran EM, Welshons WV, Wei HS, Davuluri RV, Plass C, Nephew KP, Huang TH-M. 2004  Loss of estrogen signaling triggers epigenetic silencing of downstream targets. Cancer Res 64:8184-8192
  • Fan M, Nakshatri H, Nephew KP.  2004  Inhibiting proteasomal proteolysis sustains estrogen receptor-alpha activation.  Mol Endocrinol 18:2603-2615
  • Fan M, Bigsby RM, Nephew KP. 2003 NEDD8 pathway is required for proteasome mediated degradation of human estrogen receptor-a and essential for the antiproliferation activity of ICI 182,780 in ER-positive breast cancer cells. Mol Endocrinol 17:356-365 (cover article)



Awards and Honors

  • National Institutes of Health/National Cancer Institute Grant (Nephew), 2008-2013
    Title: DNA Methylation and Ovarian Cancer
  • National Institutes of Health/National Cancer Institute Grant (Huang), 2004-2010
    Project 4 Leader, Project Title: Predicting Drug Resistance in Cancer Genomes by DNA Methylation Profiling
  • Phi Beta Psi National Sorority Research Grant, 2007-2009
    Title: Epigenetic Targeting of Ovarian Tumor Stem Cells
  • Indiana University Melvin and Brn Simon Cancer Center Translational Research Acceleration Collaboration (ITRAC) Grant, 2008-2010
    Title: WNT Modulation of Breast Cancer Stem Cell Phenotype in Bone Metastasis
  • National Institutes of Health/National Cancer Institute Grant (Matei), 2008-2010
    Co-investigator, Project Title: A low-dose decitabine (5-aza-2'- deoxycytidine) strategy for restoring ovarian cancer sensitivity to carboplatin
  • Department of Defense, CDMRP, Breast Cancer Research Program (BCRP)Predoctoral Traineeship
    Mentor, Project Title: Transforming Growth Factor Beta Signaling in Growth of Estrogen Insensitive, Metastatic Bone Lesions
  • National Institutes of Health/NIDDK Grant (Weatherman), 2007-2012
    Co-investigator, Project Title: Novel Bioconjugates as Probes of Estrogen Receptors
  • National Institutes of Health/NIAAA Grant (Zhou), 2006-2010
    Co-investigator, Project Title: Epigenetics of Fetal Alcohol Syndrome
  • Indiana University Simon Cancer Center Grant (Noah Hahn, MD), 2008-2009
    Co-investigator, Project Title: In Vivo Study of Intravesical 5-azacitidine for the Treatment of Urinary Bladder Cancer


  • American Association for Cancer Research
  • American Association for the Advancement of Science
  • Endocrine Society
  • Epigenetics Society
  • Society for Gynecologic Investigation
  • Society for the Study of Reproduction


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