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Gioeli, Daniel

Daniel Gioeli

Primary Appointment

Microbiology, Immunology, and Cancer Biology

Contact Information

PO Box 801318
Charlottesvillle, VA 22908
Telephone: 434-982-4243
Email: dgg3f@virginia.edu
Website: http://mic.med.virginia.edu/gioeli/

Research Interests

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

Danan D, Lehman CE, Mendez RE, Langford B, Koors PD, Dougherty MI, Peirce SM, Gioeli DG, Jameson MJ, Effect of Adipose-Derived Stem Cells on Head and Neck Squamous Cell Carcinoma., 2018; Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 158(5) 882-888 PMID: 29313435 |

Lu H, Wang T, Li J, Fedele C, Liu Q, Zhang J, Jiang Z, Jain D, Iozzo RV, Violette SM, Weinreb PH, Davis RJ, Gioeli D, Fitzgerald TJ, Altieri DC, Languino LR, ?v?6 Integrin Promotes Castrate-Resistant Prostate Cancer Through JNK1-Mediated Activation of Androgen Receptor., 2016; Cancer research. () PMID: 27450452 |

Benamar M, Guessous F, Du K, Corbett P, Obeid J, Gioeli D, Slingluff CL, Abbas T, Inactivation of the CRL4-CDT2-SET8/p21 ubiquitylation and degradation axis underlies the therapeutic efficacy of pevonedistat in melanoma., 2016; EBioMedicine. () PMID: 27333051 |

Roller DG, Capaldo B, Bekiranov S, Mackey AJ, Conaway MR, Petricoin EF, Gioeli D, Weber MJ, Combinatorial drug screening and molecular profiling reveal diverse mechanisms of intrinsic and adaptive resistance to BRAF inhibition in V600E BRAF mutant melanomas., 2015; Oncotarget. 7(3) 2734-53 PMID: 26673621 | PMCID: PMC4823068

Zboray L, Pluciennik A, Curtis D, Liu Y, Berman-Booty LD, Orr C, Kesler CT, Berger T, Gioeli D, Paschal BM, Merry DE, Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA., 2015; Cell reports. 13(10) 2312-23 PMID: 26673324 | PMCID: PMC4684905

Ta HQ, Ivey ML, Frierson HF, Conaway MR, Dziegielewski J, Larner JM, Gioeli D, Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth., 2015; Cancer research. 75(23) 5093-105 PMID: 26573794 | PMCID: PMC4668217

Capaldo BJ, Roller D, Axelrod MJ, Koeppel AF, Petricoin EF, Slingluff CL, Weber MJ, Mackey AJ, Gioeli D, Bekiranov S, Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma., 2015; PloS one. 10(9) e0138210 PMID: 26405815 | PMCID: PMC4583389

Koryakina Y, Knudsen KE, Gioeli D, Cell-cycle-dependent regulation of androgen receptor function., 2015; Endocrine-related cancer. 22(2) 249-64 PMID: 25691442 | PMCID: PMC4382102

Ta HQ, Gioeli D, The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer., 2014; Endocrine-related cancer. 21(5) R395-407 PMID: 25096064 | PMCID: PMC4382101

Axelrod MJ, Gordon V, Mendez RE, Leimgruber SS, Conaway MR, Sharlow ER, Jameson MJ, Gioeli DG, Weber MJ, p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling networks., 2014; Cellular signalling. () PMID: 24662264 | PMCID: PMC4091927

Axelrod MJ, Mendez RE, Khalil A, Leimgruber SS, Sharlow ER, Capaldo B, Conaway M, Gioeli DG, Weber MJ, Jameson MJ, 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., 2014; Head & neck. () PMID: 24986420 |

Axelrod M, Gordon VL, Conaway M, Tarcsafalvi A, Neitzke DJ, Gioeli D, Weber MJ, Combinatorial drug screening identifies compensatory pathway interactions and adaptive resistance mechanisms., 2013; Oncotarget. 4(4) 622-35 PMID: 23599172 | PMCID: PMC3720609

Roller D, Axelrod M, Capaldo B, Jensen K, Mackey A, Weber MJ, Gioeli D, Synthetic lethal screening with small molecule inhibitors provides a pathway to rational combination therapies for melanoma., 2012; Molecular cancer therapeutics. () 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., 2012; PloS one. 7(6) e38950 PMID: 22761715 | PMCID: PMC3384611

Gioeli D, Wunderlich W, Sebolt-Leopold J, Bekiranov S, Wulfkuhle JD, Petricoin EF, Conaway M, Weber MJ, Compensatory pathways induced by MEK inhibition are effective drug targets for combination therapy against castration-resistant prostate cancer., 2011; Molecular cancer therapeutics. 10(9) 1581-90 PMID: 21712477 | PMCID: PMC3315368

Ni L, Yang CS, Gioeli D, Frierson H, Toft DO, Paschal BM, FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells., 2010; Molecular and cellular biology. 30(5) 1243-53 PMID: 20048054 | PMCID: PMC2820886

Gordon V, Bhadel S, Wunderlich W, Zhang J, Ficarro SB, Mollah SA, Shabanowitz J, Hunt DF, Xenarios I, Hahn WC, Conaway M, Carey MF, Gioeli D, CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation., 2010; Molecular endocrinology (Baltimore, Md.). 24(12) 2267-80 PMID: 20980437 | PMCID: PMC2999477

Tilghman RW, Cowan CR, Mih JD, Koryakina Y, Gioeli D, Slack-Davis JK, Blackman BR, Tschumperlin DJ, Parsons JT, Matrix rigidity regulates cancer cell growth and cellular phenotype., 2010; PloS one. 5(9) e12905 PMID: 20886123 | PMCID: PMC2944843

Kelley JB, Talley AM, Spencer A, Gioeli D, Paschal BM, Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors., 2010; BMC cell biology. 11() 63 PMID: 20701745 | PMCID: PMC2929220

DaSilva J, Gioeli D, Weber MJ, Parsons SJ, The neuroendocrine-derived peptide parathyroid hormone-related protein promotes prostate cancer cell growth by stabilizing the androgen receptor., 2009; Cancer research. 69(18) 7402-11 PMID: 19706771 | PMCID: PMC2803023

Wu Z, Gioeli D, Conaway M, Weber MJ, Theodorescu D, Restoration of PTEN expression alters the sensitivity of prostate cancer cells to EGFR inhibitors., 2008; The Prostate. 68(9) 935-44 PMID: 18386291 | PMCID: PMC2748221

Kesler CT, Gioeli D, Conaway MR, Weber MJ, Paschal BM, Subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor., 2007; Molecular endocrinology (Baltimore, Md.). 21(9) 2071-84 PMID: 17579212 |

Bigler D, Gioeli D, Conaway MR, Weber MJ, Theodorescu D, Rap2 regulates androgen sensitivity in human prostate cancer cells., 2007; The Prostate. 67(14) 1590-9 PMID: 17918750 |

Wu Z, Conaway M, Gioeli D, Weber MJ, Theodorescu D, Conditional expression of PTEN alters the androgen responsiveness of prostate cancer cells., 2006; The Prostate. 66(10) 1114-23 PMID: 16637073 |

Gioeli D, Black BE, Gordon V, Spencer A, Kesler CT, Eblen ST, Paschal BM, Weber MJ, Stress kinase signaling regulates androgen receptor phosphorylation, transcription, and localization., 2005; Molecular endocrinology (Baltimore, Md.). 20(3) 503-15 PMID: 16282370 |

Bakin RE, Gioeli D, Bissonette EA, Weber MJ, Attenuation of Ras signaling restores androgen sensitivity to hormone-refractory C4-2 prostate cancer cells., 2003; Cancer research. 63(8) 1975-80 PMID: 12702591 |

Gioeli D, Ficarro SB, Kwiek JJ, Aaronson D, Hancock M, Catling AD, White FM, Christian RE, Settlage RE, Shabanowitz J, Hunt DF, Weber MJ, Androgen receptor phosphorylation. Regulation and identification of the phosphorylation sites., 2002; The Journal of biological chemistry. 277(32) 29304-14 PMID: 12015328 |