Noel Warfel, PhD

Research Assistant Professor, Cellular and Molecular Medicine
Research Interests: 

Hypoxia is arguably the most well established characteristic of solid tumors that has yet to be effectively targeted therapeutically, and it is a significant obstacle to the successful treatment of cancer. Hypoxia is a reduction in the normal level of tissue oxygen that occurs in tumors due to poor blood flow and the aberrant development of new blood vessels. In response to hypoxia, cancer cells take particular advantage of their ability to activate the hypoxia-inducible factor 1 (HIF-1) transcription factor. HIF-1 increases the expression of genes that promote survival and angiogenesis, and it is associated with poor prognosis and resistance to therapy in various types of cancer. As a result, inhibiting the activity of hypoxia-inducible factors that stimulate tumor growth is currently a major objective of anticancer therapy; most notably the use of antibodies and tyrosine kinase inhibitors to block VEGF activity. While these agents display antitumor activity, they do not markedly inhibit tumor growth or induce massive tumor regression. Therefore, new strategies are needed to inhibit the expression of hypoxia-inducible genes that stimulate tumor growth. The current focus of my lab is to develop novel approaches to target the hypoxic tumor microenvironment.  Our goal is to understand the complex signaling networks that control hypoxia-mediated therapeutic resistance in solid tumors and translate these basic concepts to clinical applications that will directly impact patient care. 

Molecular Medicine Grad Program: 
Yes

Bibliography

2016

Warfel, N. A., A. G. Sainz, J. H. Song, and A. S. Kraft, "PIM kinase inhibitors kill hypoxic tumor cells by reducing Nrf2 signaling and increasing reactive oxygen species.", Mol Cancer Ther, 2016 May 16. PMID: 27196781

2015

Warfel, N. A., and A. S. Kraft, "PIM kinase (and Akt) biology and signaling in tumors.", Pharmacol Ther, vol. 151, pp. 41-9, 2015 Jul. PMID: 25749412
Zhang, S., L. Zhou, B. Hong, P. J. A van den Heuvel, V. V. Prabhu, N. A. Warfel, C. Leah B. Kline, D. T. Dicker, L. Kopelovich, and W. S. El-Deiry, "Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53.", Cancer Res, vol. 75, issue 18, pp. 3842-52, 2015 Sep 15. PMCID: PMC4573895  PMID: 26294215

2014

Warfel, N. A., and W. S. El-Deiry, "HIF-1 signaling in drug resistance to chemotherapy.", Curr Med Chem, vol. 21, issue 26, pp. 3021-8, 2014. PMID: 24735366

2013

Warfel, N. A., N. G. Dolloff, D. T. Dicker, J. Malysz, and W. S. El-Deiry, "CDK1 stabilizes HIF-1α via direct phosphorylation of Ser668 to promote tumor growth.", Cell Cycle, vol. 12, issue 23, pp. 3689-701, 2013 Dec 1. PMCID: PMC3903720  PMID: 24189531
Warfel, N. A., and W. S. El-Deiry, "p21WAF1 and tumourigenesis: 20 years after.", Curr Opin Oncol, vol. 25, issue 1, pp. 52-8, 2013 Jan. PMID: 23159848

2012

Warfel, N. A., and A. C. Newton, "Pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP): a new player in cell signaling.", J Biol Chem, vol. 287, issue 6, pp. 3610-6, 2012 Feb 3. PMCID: PMC3281723  PMID: 22144674
Prabhu, V. V., N. A. Warfel, and W. S. El-Deiry, "CTGF-mediated autophagy-senescence transition in tumor stroma promotes anabolic tumor growth and metastasis.", Cell Cycle, vol. 11, issue 14, pp. 2592-3, 2012 Jul 15. PMCID: PMC3409005  PMID: 22751431

2011

Warfel, N. A., M. Niederst, and A. C. Newton, "Disruption of the interface between the pleckstrin homology (PH) and kinase domains of Akt protein is sufficient for hydrophobic motif site phosphorylation in the absence of mTORC2.", J Biol Chem, vol. 286, issue 45, pp. 39122-9, 2011 Nov 11. PMCID: PMC3234737  PMID: 21908613
Warfel, N. A., M. Niederst, M. W. Stevens, P. M. Brennan, M. C. Frame, and A. C. Newton, "Mislocalization of the E3 ligase, β-transducin repeat-containing protein 1 (β-TrCP1), in glioblastoma uncouples negative feedback between the pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and Akt.", J Biol Chem, vol. 286, issue 22, pp. 19777-88, 2011 Jun 3. PMCID: PMC3103356  PMID: 21454620

2009

Brognard, J., M. Niederst, G. Reyes, N. Warfel, and A. C. Newton, "Common polymorphism in the phosphatase PHLPP2 results in reduced regulation of Akt and protein kinase C.", J Biol Chem, vol. 284, issue 22, pp. 15215-23, 2009 May 29. PMCID: PMC2685702  PMID: 19324870

2007

Gills, J. J., J. Lopiccolo, J. Tsurutani, R. H. Shoemaker, C. J. M. Best, M. S. Abu-Asab, J. Borojerdi, N. A. Warfel, E. R. Gardner, M. Danish, et al., "Nelfinavir, A lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo.", Clin Cancer Res, vol. 13, issue 17, pp. 5183-94, 2007 Sep 1. PMID: 17785575
Granville, C. A., N. Warfel, J. Tsurutani, C. M Hollander, M. Robertson, S. D. Fox, T. D. Veenstra, H. J. Issaq, I. R Linnoila, and P. A. Dennis, "Identification of a highly effective rapamycin schedule that markedly reduces the size, multiplicity, and phenotypic progression of tobacco carcinogen-induced murine lung tumors.", Clin Cancer Res, vol. 13, issue 7, pp. 2281-9, 2007 Apr 1. PMID: 17404113
Gills, J. J., S. S Castillo, C. Zhang, P. A. Petukhov, R. M. Memmott, M. Hollingshead, N. Warfel, J. Han, A. P. Kozikowski, and P. A. Dennis, "Phosphatidylinositol ether lipid analogues that inhibit AKT also independently activate the stress kinase, p38alpha, through MKK3/6-independent and -dependent mechanisms.", J Biol Chem, vol. 282, issue 37, pp. 27020-9, 2007 Sep 14. PMID: 17631503

2006

Warfel, N. A., E. R. Lepper, C. Zhang, W. D. Figg, and P. A. Dennis, "Importance of the stress kinase p38alpha in mediating the direct cytotoxic effects of the thalidomide analogue, CPS49, in cancer cells and endothelial cells.", Clin Cancer Res, vol. 12, issue 11 Pt 1, pp. 3502-9, 2006 Jun 1. PMID: 16740776