- Biomedical Sciences Graduate Program | Daniel Gioeli

Daniel Gioeli

Education

  • PhD, University of North Carolina

Primary Appointment

  • Associate Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Signal transduction in cancer cells

Research Description

Overview.

My primary research interest has focused on understanding the mechanistic underpinnings of the cell signaling networks that contribute to cancer progression and resistance to therapy. My laboratory is currently focused on two research areas:

1) We are testing the hypothesis that progression of prostate cancer to castration-resistance is frequently driven by changes in CHK2 signaling that regulate androgen receptor (AR) activity, facilitate cell proliferation, and minimize hormone dependence. These studies will uncover new information on how kinases regulate the AR and will reveal mechanistic information critical for the rational application of existing and novel therapies for (castration-resistant prostate cancer (CRPC).

2) We are developing an in vitro tumor microenvironment system for solid tumors that utilizes multiple cell types and recapitulates tumor capillary hemodynamics and biological transport. The applicability of this system is multifaceted and includes facilitating drug discovery and development, mechanistic analysis of drug responses, and development of biomarkers of response.

In addition to the two above focus areas, my collaborative interactions are focused on the molecular mechanisms of combinations of targeted molecular agents in order to overcome inherent and acquired resistance associated with traditional therapeutic approaches.

For the more detailed descriptions please go to: Gioeli Lab Site

Selected Publications

  • Benamar M, Guessous F, Du K, Corbett P, Obeid J, Gioeli D, Slingluff C, Abbas T. Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma. EBioMedicine. 2016. PMID: 27333051
  • Lu H, Wang T, Li J, Fedele C, Liu Q, Zhang J, Jiang Z, Jain D, Iozzo R, Violette S, Weinreb P, Davis R, Gioeli D, Fitzgerald T, Altieri D, Languino L. αvβ6 Integrin Promotes Castrate-Resistant Prostate Cancer Through JNK1-Mediated Activation of Androgen Receptor. Cancer research. 2016. PMID: 27450452
  • Capaldo B, Roller D, Axelrod M, Koeppel A, Petricoin E, Slingluff C, Weber M, Mackey A, Gioeli D, Bekiranov S. Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma. PloS one. 2015;10(9): e0138210. PMID: 26405815 | PMCID: PMC4583389
  • Koryakina Y, Knudsen K, Gioeli D. Cell-cycle-dependent regulation of androgen receptor function. Endocrine-related cancer. 2015;22(2): 249-64. PMID: 25691442 | PMCID: PMC4382102
  • Roller D, Capaldo B, Bekiranov S, Mackey A, Conaway M, Petricoin E, Gioeli D, Weber M. Combinatorial drug screening and molecular profiling reveal diverse mechanisms of intrinsic and adaptive resistance to BRAF inhibition in V600E BRAF mutant melanomas. Oncotarget. 2015;7(3): 2734-53. PMID: 26673621 | PMCID: PMC4823068
  • Ta H, Ivey M, Frierson H, Conaway M, Dziegielewski J, Larner J, Gioeli D. Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth. Cancer research. 2015;75(23): 5093-105. PMID: 26573794 | PMCID: PMC4668217
  • Zboray L, Pluciennik A, Curtis D, Liu Y, Berman-Booty L, Orr C, Kesler C, Berger T, Gioeli D, Paschal B, Merry D. Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA. Cell reports. 2015;13(10): 2312-23. PMID: 26673324 | PMCID: PMC4684905
  • Axelrod M, Gordon V, Mendez R, Leimgruber S, Conaway M, Sharlow E, Jameson M, Gioeli D, Weber M. p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling networks. Cellular signalling. 2014. PMID: 24662264 | PMCID: PMC4091927
  • Axelrod M, Mendez R, Khalil A, Leimgruber S, Sharlow E, Capaldo B, Conaway M, Gioeli D, Weber M, Jameson M. Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways. Head & neck. 2014. PMID: 24986420
  • Ta H, Gioeli D. The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer. Endocrine-related cancer. 2014;21(5): R395-407. PMID: 25096064 | PMCID: PMC4382101
  • Axelrod M, Gordon V, Conaway M, Tarcsafalvi A, Neitzke D, Gioeli D, Weber M. Combinatorial drug screening identifies compensatory pathway interactions and adaptive resistance mechanisms. Oncotarget. 2013;4(4): 622-35. PMID: 23599172 | PMCID: PMC3720609
  • Roller D, Axelrod M, Capaldo B, Jensen K, Mackey A, Weber M, Gioeli D. Synthetic lethal screening with small molecule inhibitors provides a pathway to rational combination therapies for melanoma. Molecular cancer therapeutics. 2012. PMID: 22962324 | PMCID: NIHMS405900
  • Whitworth H, Bhadel S, Ivey M, Conaway M, Spencer A, Hernan R, Holemon H, Gioeli D. Identification of kinases regulating prostate cancer cell growth using an RNAi phenotypic screen. PloS one. 2012;7(6): e38950. PMID: 22761715 | PMCID: PMC3384611
  • Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle J, Petricoin E, Conaway M, Weber M. Compensatory pathways induced by MEK inhibition are effective drug targets for combination therapy against castration-resistant prostate cancer. Molecular cancer therapeutics. 2011;10(9): 1581-90. PMID: 21712477 | PMCID: PMC3315368
  • Gordon V, Bhadel S, Wunderlich W, Zhang J, Ficarro S, Mollah S, Shabanowitz J, Hunt D, Xenarios I, Hahn W, Conaway M, Carey M, Gioeli D. CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Molecular endocrinology (Baltimore, Md.). 2010;24(12): 2267-80. PMID: 20980437 | PMCID: PMC2999477
  • Kelley J, Talley A, Spencer A, Gioeli D, Paschal B. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors. BMC cell biology. 2010;11 63. PMID: 20701745 | PMCID: PMC2929220
  • Ni L, Yang C, Gioeli D, Frierson H, Toft D, Paschal B. FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Molecular and cellular biology. 2010;30(5): 1243-53. PMID: 20048054 | PMCID: PMC2820886
  • Tilghman R, Cowan C, Mih J, Koryakina Y, Gioeli D, Slack-Davis J, Blackman B, Tschumperlin D, Parsons J. Matrix rigidity regulates cancer cell growth and cellular phenotype. PloS one. 2010;5(9): e12905. PMID: 20886123 | PMCID: PMC2944843
  • DaSilva J, Gioeli D, Weber M, Parsons S. The neuroendocrine-derived peptide parathyroid hormone-related protein promotes prostate cancer cell growth by stabilizing the androgen receptor. Cancer research. 2009;69(18): 7402-11. PMID: 19706771 | PMCID: PMC2803023
  • Wu Z, Gioeli D, Conaway M, Weber M, Theodorescu D. Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitors. The Prostate. 2008;68(9): 935-44. PMID: 18386291 | PMCID: PMC2748221
  • Bigler D, Gioeli D, Conaway M, Weber M, Theodorescu D. Rap2 regulates androgen sensitivity in human prostate cancer cells. The Prostate. 2007;67(14): 1590-9. PMID: 17918750
  • Kesler C, Gioeli D, Conaway M, Weber M, Paschal B. Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor. Molecular endocrinology (Baltimore, Md.). 2007;21(9): 2071-84. PMID: 17579212
  • Wu Z, Conaway M, Gioeli D, Weber M, Theodorescu D. Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells. The Prostate. 2006;66(10): 1114-23. PMID: 16637073
  • Gioeli D, Black B, Gordon V, Spencer A, Kesler C, Eblen S, Paschal B, Weber M. Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localization. Molecular endocrinology (Baltimore, Md.). 2005;20(3): 503-15. PMID: 16282370
  • Bakin R, Gioeli D, Bissonette E, Weber M. Attenuation of Ras signaling restores androgen sensitivity to hormone-refractory C4-2 prostate cancer cells. Cancer research. 2003;63(8): 1975-80. PMID: 12702591
  • Gioeli D, Ficarro S, Kwiek J, Aaronson D, Hancock M, Catling A, White F, Christian R, Settlage R, Shabanowitz J, Hunt D, Weber M. Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites. The Journal of biological chemistry. 2002;277(32): 29304-14. PMID: 12015328