Dawn E. Quelle, PhD

Portrait
Associate Professor of Pharmacology
Associate Professor of Pathology

Contact Information

Primary Office
2-570 BSB
51 Newton Rd.
Iowa City, IA 52242
319-353-5749

Lab
2-551 BSB
Iowa City, IA 52242
319-335-7663

Education

BS, Biochemistry, University of Maine, Orono
PhD, Molecular & Cell Biology, The Pennsylvania State University, University Park
Fellow, The Pennsylvania State University
Postdoctoral Fellow, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Molecular Medicine, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Research Summary

Molecular Mechanisms of Tumorigenesis and Cell Cycle Control My research is centered on understanding molecular mechanisms that control cell proliferation and checkpoint responses, and how those processes are disrupted during tumorigenesis. A principal focus of the lab is the ARF tumor suppressor, which is encoded by a gene (INK4a/ARF) that is inactivated in 40-50% of all human cancers. ARF inhibits tumorigenesis through p53-dependent and p53-independent signaling pathways that are complex and only partially defined. That is because ARF functions through numerous binding partners (at least 30) to promote apoptosis or senescence, inhibit migration/invasion and metastasis, sustain cell stress checkpoints and maintain chromosomal stability. Our goal is to define the critical regulators of ARF signaling and determine their significance to tumor suppression using molecular approaches and in vivo models of cancer. In so doing, we will advance our fundamental understanding of ARF-mediated tumor suppression and also identify novel regulators of growth (both positive and negative) whose characterization will likely contribute to new paradigms of carcinogenesis. Such knowledge is essential to providing new markers for tumor detection and developing useful, targeted anticancer strategies.

Publications

Uthoff, J., De Stefano, F. A., Panzer, K., Darbro, B. W., Sato, T. S., Khanna, R., Quelle, D. E., Meyerholz, D. K., Weimer, J. & Sieren, J. C. (2018). Radiomic biomarkers informative of cancerous transformation in neurofibromatosis-1 plexiform tumors. Journal of Neuroradiology. PMID: 29958847.

White, K. A., Swier, V. J., Cain, J. T., Kohlmeyer, J. L., Meyerholz, D. K., Tanas, M. R., Uthoff, J., Hammond, E., Li, H., Rohret, F. A., Goeken, A., Chan, C. H., Leidinger, M. R., Umesalma, S., Wallace, M. R., Dodd, R. D., Panzer, K., Tang, A. H., Darbro, B. W., Moutal, A., Cai, S., Li, W., Bellampalli, S. S., Khanna, R., *Rogers, C. S., *Sieren, J. C., *Quelle, D. E. & *Weimer, J. M. (2018). A porcine model of neurofibromatosis type 1 that mimics the human disease. JCI insight, 3(12). PMID: 29925695.

Meyerholz, D. K., Ofori-Amanfo, G. K., Leidinger, M. R., Goeken, J. A., Khanna, R., Sieren, J. C., Darbro, B. W., Quelle, D. E. & Weimer, J. M. (2017). Immunohistochemical Markers for Prospective Studies in Neurofibromatosis-1 Porcine Models. The journal of Histochemistry and Cytochemistry, 65(10), 607-618. PMID: 28846462.

Pardo, M., Yu, L., Shen, S., Tate, P., Bode, D., Letney, B. L., Quelle, D. E., Skarnes, W. & Choudhary, J. S. (2017). Myst2/Kat7 histone acetyltransferase interaction proteomics reveals tumour-suppressor Niam as a novel binding partner in embryonic stem cells. Scientific reports, 7(1), 8157. PMID: 28811661.

Hao, M., Franqui-Machin, R., Xu, H., Shaughnessy, Jr, J., Barlogie, B., Roodman, D., Quelle, D. E., Janz, S., Tomasson, M. H., Sanderson, R. D., Qiu, L., Frech, I., Tricot, G. & Zhan, F. (2017). NEK2 induces osteoclast differentiation and bone destruction via heparanase in multiple myeloma. Leukemia, 31(7), 1648-1650. PMID: 28400617.

Quelle, D. E., Nteeba, J. & Darbro, B. W. (2016). The INK4a/ARF locus. R. Bradshaw , P. Stahl (Eds.) pp. 447-457. In: Encyclopedia of Cell Biology, (Bradshaw, R. and Stahl, P., Eds.). Waltham, MA: Academic Press.

Hagen, J., Muniz, V. P., Falls, K., Reed, S. M., Taghiyev, A. F., Quelle, F. W., Gourronc, F., Klingelhutz, A. J., Major, H. J., Askeland, R., Sherman, S. K., O'Dorisio, T. M., Bellizzi, A. M., Howe, J. R., Darbro, B. W. & Quelle, D. E. (2014). RABL6A promotes G1-S phase progression and pancreatic neuroendocrine tumor cell proliferation in an Rb1-dependent manner. Cancer Research, 74(22), 6661-6670. PMID: 25273089.

Reed, S. M., Hagen, J., Muniz, V. P., Rosean, T. R., Borcherding, N., Scieqienka, S., Goeken, J. A., Naumann, P. W., Zhang, W., Tompkins, V. S., Janz, S., Meyerholz, D. K. & Quelle, D. E. (2014). NIAM-deficient mice are predisposed to the development of proliferative lesions including B-cell lymphomas. PLoS One, 9(11), e112126. PMID: 25393878.

Sieren, J. C., Meyerholz, D. K., Wang, X. J., Davis, B. T., Newell, J. D., Hammond, E., Rohret, J. A., Rohret, F. A., Struzynski, J. T., Goeken, J. A., Naumann, P. W., Leidinger, M. R., Taghiyev, A., Van Rheeden, R., Hagen, J., Darbro, B. W., Quelle, D. E. & Rogers, C. S. (2014). Development and translational imaging of a TP53 porcine tumorigenesis model. J of Clinical Investigation, 124(9), 4052-4066. PMID: 25105366.

Reed, S. M., Quelle, F. W. & Quelle, D. E. (2014). ARF sees Pdgfrß through the miR. Cell Cycle, 13(10), 1520-1521. PMID: 24755551.

Reed, S. M., Hagen, J., Tompkins, V. S., Thies, K., Quelle, F. W. & Quelle, D. E. (2014). Nuclear Interactor of ARF and Mdm2 regulates multiple pathways to activate p53. PMID: 24621507.

Reed, S. M., Quelle, D. E. (2014). p53 Acetylation: Regulation and Consequences. Cancers, 7(1), 30-69. PMID: 25545885.

Huang, J., Stewart, A., Maity, B., Hagen, J., Hagen, R. L., Quelle, D. E., Brenner, C. & Fisher, R. F. (2014). RGS6 suppresses Ras-induced cellular transformation by facilitating Tip60-mediated Dnmt1 degradation and promoting apoptosis. Oncogene, 33(27), 3604-11. PMID: 23995786.

Sieren, J. C., Quelle, D. E., Meyerholz, D. K. & Rogers, C. S. (2014). Porcine cancer models for translational oncology. Molecular & Cellular Oncology, 1(4), e969626. PMID: 27308376.

Muniz, V. P., Askeland, R. A., Zhang, X., Reed, S. M., Tompkins, V., Hagen, J., Button, A., Smith, B. J., Zamba, G., Weydert, J. A., Mezhir, J. & Quelle, D. E. (2013). RABL6A promotes oxaliplatin resistance in tumor cells and is a new marker of survival for resected pancreatic ductal adenocarcinoma patients. Genes & Cancer, 4(7-8), 273-284. PMID: 24167655.

Zhang, X., Hagen, J., Muniz, V. P., Smith, T., Coombs, G., Eischen, C. M., Mackie, D., Roman, D., Van Rheeden, R., Darbro, B. & Quelle, D. E. (2013). RABL6A, a novel RAB-like protein, controls centrosome amplification and chromosome instability in primary fibroblasts. PLoS ONE, 8(11), e80228. PMID: 24282525.

Anderson, M. G., D'Allesandro, D., Quelle, D. E., Axelson, R., Geist, L. & Black, D. W. (2013). Recognizing Diverse Forms of Scholarship in the Modern Medical College.

Muniz, V. P., Barnes, J. M., Paliwal, S., Zhang, X., Tang, X., Chen, S., Zamba, K. D., Cullen, J. J., Meyerholz, D. K., Meyers, S., Davis, J. N., Grossman, S. R., Henry, M. D. & Quelle, D. E. (2011). The ARF tumor suppressor inhibits tumor cell colonization independent of p53 in a novel mouse model of pancreatic ductal adenocarcinoma metastasis. Molecular Cancer Research, 9(7), 867-77. PMID: 21636682.

di Tommaso, A., Hagen, J., Tompkins, V., Muniz, V., Dudakovic, A., Kitzis, A., Ladeveze, V. & Quelle, D. E. (2009). Residues in the alternative reading frame tumor suppressor that influence its stability and p53-independent activities. Experimental cell research, 315(7), 1326-35. PMID: 19331830.

Hagen, J., Tompkins, V., Dudakovic, A., Weydert, J. A. & Quelle, D. E. (2008). Generation and characterization of monoclonal antibodies to NIAM: a nuclear interactor of ARF and Mdm2. Hybridoma (Larchmt), 27(3), 159-66. PMID: 18582208.

Groskreutz, D. J., Monick, M. M., Yarovinsky, T. O., Powers, L. S., Quelle, D. E., Varga, S. M., Look, D. C. & Hunninghake, G. W. (2007). Respiratory syncytial virus decreases p53 protein to prolong survival of airway epithelial cells. Journal of immunology, 179(5), 2741-7. PMID: 17709487.

Tompkins, V. S., Hagen, J., Frazier, A. A., Lushnikova, T., Fitzgerald, M. P., di Tommaso, A., Ladeveze, V., Domann, F. E., Eischen, C. M. & Quelle, D. E. (2007). A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains chromosomal stability. The Journal of biological chemistry, 282(2), 1322-33. PMID: 17110379.

Tompkins, V., Hagen, J., Zediak, V. P. & Quelle, D. E. (2006). Identification of novel ARF binding proteins by two-hybrid screening. Cell cycle, 5(6), 641-6. PMID: 16582619.

Miller, S. J., Rangwala, F., Williams, J., Ackerman, P., Kong, S., Jegga, A. G., Kaiser, S., Aronow, B. J., Frahm, S., Kluwe, L., Mautner, V., Upadhyaya, M., Muir, D., Wallace, M., Hagen, J., Quelle, D. E., Watson, M. A., Perry, A., Gutmann, D. H. & Ratner, N. (2006). Large-scale molecular comparison of human schwann cells to malignant peripheral nerve sheath tumor cell lines and tissues. Cancer research, 66(5), 2584-91. PMID: 16510576.

Datta, A., Sen, J., Hagen, J., Korgaonkar, C. K., Caffrey, M., Quelle, D. E., Hughes, D. E., Ackerson, T. J., Costa, R. H. & Raychaudhuri, P. (2005). ARF directly binds DP1: interaction with DP1 coincides with the G1 arrest function of ARF. Molecular and cellular biology, 25(18), 8024-36. PMID: 16135794.

Korgaonkar, C., Hagen, J., Tompkins, V., Frazier, A. A., Allamargot, C., Quelle, F. W. & Quelle, D. E. (2005). Nucleophosmin (B23) targets ARF to nucleoli and inhibits its function. Molecular and cellular biology, 25(4), 1258-71. PMID: 15684379.

Zhao, L., Samuels, T., Winckler, S., Korgaonkar, C., Tompkins, V., Horne, M. C. & Quelle, D. E. (2003). Cyclin G1 has growth inhibitory activity linked to the ARF-Mdm2-p53 and pRb tumor suppressor pathways. Molecular cancer research : MCR, 1(3), 195-206. PMID: 12556559.

Linggi, B., Muller-Tidow, C., van de Locht, L., Hu, M., Nip, J., Serve, H., Berdel, W. E., van der Reijden, B., Quelle, D. E., Rowley, J. D., Cleveland, J., Jansen, J. H., Pandolfi, P. P. & Hiebert, S. W. (2002). The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nature medicine, 8(7), 743-50. PMID: 12091906.

Korgaonkar, C., Zhao, L., Modestou, M. & Quelle, D. E. (2002). ARF function does not require p53 stabilization or Mdm2 relocalization. Molecular and cellular biology, 22(1), 196-206. PMID: 11739734.

Eapen, A. K., Henry, M. K., Quelle, D. E. & Quelle, F. W. (2001). Dna damage-induced G(1) arrest in hematopoietic cells is overridden following phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2. Molecular and cellular biology, 21(18), 6113-21. PMID: 11509654.

Modestou, M., Puig-Antich, V., Korgaonkar, C., Eapen, A. & Quelle, D. E. (2001). The alternative reading frame tumor suppressor inhibits growth through p21-dependent and p21-independent pathways. Cancer research, 61(7), 3145-50. PMID: 11306500.

Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G. & Sherr, C. J. (1997). Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell, 91(5), 649-59. PMID: 9393858.

Zindy, F., Quelle, D. E., Roussel, M. F. & Sherr, C. J. (1997). Expression of the p16INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene, 15(2), 203-11. PMID: 9244355.

Quelle, D. E., Cheng, M., Ashmun, R. A. & Sherr, C. J. (1997). Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by p16INK4a but not by the alternative reading frame protein p19ARF. Proc Natl Acad Sci USA, 94(2), 669-73. PMID: 9012842.

Quelle, D. E., Zindy, F., Ashmun, R. A. & Sherr, C. J. (1995). Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell, 83(6), 993-1000. PMID: 8521522.

Linardopoulos, S., Street, A. J., Quelle, D. E., Parry, D., Peters, G., Sherr, C. J. & Balmain, A. (1995). Deletion and altered regulation of p16INK4a and p15INK4b in undifferentiated mouse skin tumors. Cancer research, 55(22), 5168-72. PMID: 7585567.

Quelle, D. E., Ashmun, R. A., Hannon, G. J., Rehberger, P. A., Trono, D., Richter, K. H., Walker, C., Beach, D., Sherr, C. J. & Serrano, M. (1995). Cloning and characterization of murine p16INK4a and p15INK4b genes. Oncogene, 11(4), 635-45. PMID: 7651726.

He, T. C., Jiang, N., Zhuang, H., Quelle, D. E. & Wojchowski, D. M. (1994). The extended box 2 subdomain of erythropoietin receptor is nonessential for Jak2 activation yet critical for efficient mitogenesis in FDC-ER cells. The Journal of biological chemistry, 269(28), 18291-4. PMID: 8034573.

Matsushime, H., Quelle, D. E., Shurtleff, S. A., Shibuya, M., Sherr, C. J. & Kato, J. Y. (1994). D-type cyclin-dependent kinase activity in mammalian cells. Molecular and cellular biology, 14(3), 2066-76. PMID: 8114738.

Sherr, C. J., Matsushime, H., Kato, J. Y., Quelle, D. E. & Roussel, M. F. (1994). Control of G1 progression by mammalian D-type cyclins. V. Hu (Eds.) pp. 17-23. In: The Cell Cycle (Hu, V., Ed.). New York, Plenum Press.

Sherr, C. J., Kato, J., Quelle, D. E., Matsuoka, M. & Roussel, M. F. (1994). D-type cyclins and their cyclin-dependent kinases: G1 phase integrators of the mitogenic response. Cold Spring Harbor symposia on quantitative biology, 59, 11-9. PMID: 7587060.

Quelle, D. E., Ashmun, R. A., Shurtleff, S. A., Kato, J. Y., Bar-Sagi, D., Roussel, M. F. & Sherr, C. J. (1993). Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes & development, 7(8), 1559-71. PMID: 8339933.

Sherr, C. J., Quelle, D. E., Kato, J. Y., Shurtleff, S. A. & Roussel, M. F. (1993). D-type cyclins and G1 progression. pp. 223-224. In: Euromedicine 93, 9emes Rencontres Interanationales de Recherches et de Technologies Medicales et Pharmaceutiques. Paris: SN Editel.

Quelle, D. E., Lynch, K. J., Burkert-Smith, R. E., Weiss, S., Whitford, W. & Wojchowski, D. M. (1992). Phosphorylatable and epitope-tagged human erythropoietins: utility and purification of native baculovirus-derived forms. Protein expression and purification, 3(6), 461-9. PMID: 1283094.

Quelle, D. E., Quelle, F. W. & Wojchowski, D. M. (1992). Mutations in the WSAWSE and cytosolic domains of the erythropoietin receptor affect signal transduction and ligand binding and internalization. Molecular and cellular biology, 12(10), 4553-61. PMID: 1406645.

Quelle, F. W., Quelle, D. E. & Wojchowski, D. M. (1992). Interleukin 3, granulocyte-macrophage colony-stimulating factor, and transfected erythropoietin receptors mediate tyrosine phosphorylation of a common cytosolic protein (pp100) in FDC-ER cells. The Journal of biological chemistry, 267(24), 17055-60. PMID: 1324920.

Quelle, D. E., Wojchowski, D. M. (1991). Localized cytosolic domains of the erythropoietin receptor regulate growth signaling and down-modulate responsiveness to granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci USA, 88(11), 4801-5. PMID: 1711211.