Radiation Oncology

Aloysius J. Klingelhutz, PhD

Portrait

Associate Professor of Microbiology
Associate Professor of Radiation Oncology

Contact Information

Office: 2202 Medical Education and Research Facility
375 Newton Rd
Iowa City, IA 52242
Office Phone: 319-335-7788

Lab: 2216 Medical Education and Research Facility
375 Newton Rd
Iowa City, IA 52242
Phone: 319-335-8499

Email: al-klingelhutz@uiowa.edu
Web: Carver College of Medicine Interview
Web: The immortal HeLa at Iowa

Education

BS, Biology, St John's University
PhD, Genetics, University of Wisconsin, Madison

Post Doctoral, Cancer Biology, Fred Hutchinson Cancer Research Center

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Microbiology Graduate Program
Free Radical and Radiation Biology Graduate Program
Interdisciplinary Graduate Program in Genetics
Interdisciplinary Graduate Program in Informatics
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

One of my primary interests is in how epithelial cells become immortal and subsequently malignant after infection with human papillomavirus (HPV). We are also studying how telomere loss and other factors are involved in induction of cellular senescence and aging. More recent studies have focused on the role of adipocytes in the development of diabetes and other metabolic disorders. Specific areas of research are:

-Determining how bacterial toxins and environmental pollutants disrupt metabolism through their effects on adipocyte differentiation and function

-Developing strategies to inhibit the growth of HPV transformed cells

-Defining the role of telomere loss in aging and cancer

-Characterizing how cellular genes are regulated by HPV E6 and E7 during the process of infection and transformation

Center, Program and Institute Affiliations

Cancer and Aging Program
Center for Bioinformatics and Computational Biology
Center for Gene Therapy of Cystic Fibrosis and other Genetic Diseases
Helen C. Levitt Center for Viral Pathogenesis
Holden Comprehensive Cancer Center

All Publications

Jang J, Bruse S, Huneidi S, Schrader R, Monick M, Lin Y, Carter A, Klingelhutz A, Nyunoya T.  Acrolein-Exposed Normal Human Lung Fibroblasts in Vitro: Cellular Senescence, Enhanced Telomere Erosion, and Degradation of Werner's Syndrome Protein.  Environ Health Perspect.  2014 September. 122(9):955-62.
[Link]

Gourronc F, Rockey W, Thiel W, Giangrande P, Klingelhutz A.  Identification of RNA aptamers that internalize into HPV-16 E6/E7 transformed tonsillar epithelial cells.  Virology.  2013 November. 446(1-2):325-33.
[Link]

Vu B, Gourronc F, Bernlohr D, Schlievert P, Klingelhutz A.  Staphylococcal superantigens stimulate immortalized human adipocytes to produce chemokines.  PLoS One.  2013 October 30. 8(10):e77988.
[Link]

Pereboeva L, Westin E, Patel T, Flaniken I, Lamb L, Klingelhutz A, Goldman F.  DNA damage responses and oxidative stress in dyskeratosis congenita.  PLoS One.  2013 October 4. 8(10):e76473.
[Link]

Vande Pol S, Klingelhutz A.  Papillomavirus E6 oncoproteins.  Virology.  2013 October. 445(1-2):115-37.
[Link]

Kimple R, Smith M, Blitzer G, Torres A, Martin J, Yang R, Peet C, Lorenz L, Nickel K, Klingelhutz A, Lambert P, Harari P.  Enhanced radiation sensitivity in HPV-positive head and neck cancer.  Cancer Res.  2013 August 1. 73(15):4791-800.
[Link]

Hernandez L, Flenker K, Hernandez F, Klingelhutz A, McNamera J, Giangrande P.  Methods for Evaluating Cell-Specific, Cell-Internalizing RNA Aptamers.  Pharmaceuticals (Basel).  2013 March 14. 6(3):295-319.
[Link]

Buckingham E, Goldman F, Klingelhutz A.  Dyskeratosis Congenita Dermal Fibroblasts are Defective in Supporting the Clonogenic Growth of Epidermal Keratinocytes.  Aging Dis.  2012 December. 3(6):427-37.
[Link]

Klingelhutz A, Roman A.  Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses.  Virology.  2012 March 15. 424(2):77-98.
[Link]

Bulysheva A, Bowlin G, Klingelhutz A, Yeudall W.  Low-temperature electrospun silk scaffold for in vitro mucosal modeling.  J Biomed Mater Res A.  2012 March. 100(3):757-67.
[Link]

Gourronc F, Klingelhutz A.  Therapeutic opportunities: telomere maintenance in inducible pluripotent stem cells.  Mutat Res.  2012 February 1. 730(1-2):98-105.
[Link]

Vermeer P, Bell M, Lee K, Vermeer D, Wieking B, Bilal E, Bhanot G, Drapkin R, Ganesan S, Klingelhutz A, Hendriks W, Lee J.  ErbB2, EphrinB1, Src kinase and PTPN13 signaling complex regulates MAP kinase signaling in human cancers.  PLoS One.  2012. 7(1):e30447.
[Link]

Senthikumar P, Klingelhutz A, Jacobus J, Lehmler H, Robertson L, Ludewig G.  Airborne polychlorinated biphenyls (PCBs) reduce telomerase activity and shorten telomere length in immortal human skin keratinocytes (HaCat).  Toxicol Lett.  2011 July 4. 204(1):64-70.
[Link]

Buckingham E, Klingelhutz A.  The role of telomeres in the ageing of human skin.  Exp Dermatol.  2011 April. 20(4):297-302.
[Link]

Saccoccio F, Sauer A, Cui X, Armstrong A, Habib e, Johnson D, Ryckman B, Klingelhutz A, Adler S, McVoy M.  Peptides from cytomegalovirus UL130 and UL131 proteins induce high titer antibodies that block viral entry into mucosal epithelial cells.  Vaccine.  2011 March 24. 29(15):2705-11.
[Link]

Westin E, Aykin-Burns N, Buckingham E, Spitz D, Goldman F, Klingelhutz A.  The p53/p21(WAF/CIP) pathway mediates oxidative stress and senescence in dyskeratosis congenita cells with telomerase insufficiency.  Antioxid Redox Signal.  2011 March 15. 14(6):985-97.
[Link]

Agarwal S, Loh Y, McLoughlin E, Huang J, Park I, Miller J, Huo H, Okuka M, Dos Reis R, Loewer S, Ng H, Keefe D, Goldman F, Klingelhutz A, Liu L, Daley G.  Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients.  Nature.  2010 March 11. 464(7286):292-6.
[Link]

Gourronc F, Robertson M, Herrig A, Lansdorp P, Goldman F, Klingelhutz A.  Proliferative defects in dyskeratosis congenita skin keratinocytes are corrected by expression of the telomerase reverse transcriptase, TERT, or by activation of endogenous telomerase through expression of papillomavirus E6/E7 or the telomerase RNA component, TERC.  Exp Dermatol.  2010 March. 19(3):279-88.
[Link]

Hoover A, Strand G, Nowicki P, Anderson M, Vermeer P, Klingelhutz A, Bossler A, Pottala J, Hendriks W, Lee J.  Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway.  Oncogene.  2009 November 12. 28(45):3960-70.
[Link]

Lace M, Anson J, Klingelhutz A, Lee J, Bossler A, Haugen T, Turek L.  Human papillomavirus (HPV) type 18 induces extended growth in primary human cervical, tonsillar, or foreskin keratinocytes more effectively than other high-risk mucosal HPVs.  J Virol.  2009 November. 83(22):11784-94.
[Link]

Lace M, Anson J, Klingelhutz A, Harada H, Taniguchi T, Bossler A, Haugen T, Turek L.  Interferon-beta treatment increases human papillomavirus early gene transcription and viral plasmid genome replication by activating interferon regulatory factor (IRF)-1.  Carcinogenesis.  2009 August. 30(8):1336-44.
[Link]

Nyunoya T, Monick M, Klingelhutz A, Glaser H, Cagley J, Brown C, Matsumoto E, Aykin-Burns N, Spitz D, Oshima J, Hunninghake G.  Cigarette smoke induces cellular senescence via Werner's syndrome protein down-regulation.  Am J Respir Crit Care Med.  2009 February 15. 179(4):279-87.
[Link]

Yu L, Hitchler M, Sun W, Sarsour E, Goswami P, Klingelhutz A, Domann F.  AP-2alpha Inhibits c-MYC Induced Oxidative Stress and Apoptosis in HaCaT Human Keratinocytes.  J Oncol.  2009. 2009:780874.
[Link]

Goldman F, Aubert G, Klingelhutz A, Hills M, Cooper S, Hamilton W, Schlueter A, Lambie K, Eaves C, Lansdorp P.  Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita.  Blood.  2008 May 1. 111(9):4523-31.
[Link]

Jacobus J, Flor S, Klingelhutz A, Robertson L, Ludewig G.  2-(4'-chlorophenyl)-1,4-benzoquinone increases the frequency of micronuclei and shortens telomeres.  Environ Toxicol Pharmacol.  2008 March. 25(2):267-72.
[Link]

Spanos W, Hoover A, Harris G, Wu S, Strand G, Anderson M, Klingelhutz A, Hendriks W, Bossler A, Lee J.  The PDZ binding motif of human papillomavirus type 16 E6 induces PTPN13 loss, which allows anchorage-independent growth and synergizes with ras for invasive growth.  J Virol.  2008 March. 82(5):2493-500.
[Link]

Spanos W, Geiger J, Anderson M, Harris G, Bossler A, Smith R, Klingelhutz A, Lee J.  Deletion of the PDZ motif of HPV16 E6 preventing immortalization and anchorage-independent growth in human tonsil epithelial cells.  Head Neck.  2008 February. 30(2):139-47.
[Link]

Westin E, Chavez E, Lee K, Gourronc F, Riley S, Lansdorp P, Goldman F, Klingelhutz A.  Telomere restoration and extension of proliferative lifespan in dyskeratosis congenita fibroblasts.  Aging Cell.  2007 June. 6(3):383-94.
[Link]

Hoover A, Spanos W, Harris G, Anderson M, Klingelhutz A, Lee J.  The role of human papillomavirus 16 E6 in anchorage-independent and invasive growth of mouse tonsil epithelium.  Arch Otolaryngol Head Neck Surg.  2007 May. 133(5):495-502.
[Link]

Berger K, Barriga F, Lace M, Turek L, Zamba G, Domann F, Lee J, Klingelhutz A.  Cervical keratinocytes containing stably replicating extrachromosomal HPV-16 are refractory to transformation by oncogenic H-Ras.  Virology.  2006 December. 356(1-2):68-78.
[Link]

Nyunoya T, Monick M, Klingelhutz A, Yarovinsky T, Cagley J, Hunninghake G.  Cigarette smoke induces cellular senescence.  Am J Respir Cell Mol Biol.  2006 December. 35(6):681-8.
[Link]

Darbro B, Lee K, Nguyen N, Domann F, Klingelhutz A.  Methylation of the p16(INK4a) promoter region in telomerase immortalized human keratinocytes co-cultured with feeder cells.  Oncogene.  2006 November 30. 25(56):7421-33.
[Link]

James M, Lee J, Klingelhutz A.  HPV16-E6 associated hTERT promoter acetylation is E6AP dependent, increased in later passage cells and enhanced by loss of p300.  Int J Cancer.  2006 October 15. 119(8):1878-85.
[Link]

James M, Lee J, Klingelhutz A.  Human papillomavirus type 16 E6 activates NF-kappaB, induces cIAP-2 expression, and protects against apoptosis in a PDZ binding motif-dependent manner.  J Virol.  2006 June. 80(11):5301-7.
[Link]

Klingelhutz A, Qian Q, Phillips S, Gourronc F, Darbro B, Patil S.  Amplification of the chromosome 20q region is associated with expression of HPV-16 E7 in human airway and anogenital epithelial cells.  Virology.  2005 September 30. 340(2):237-44.
[Link]

Darbro B, Schneider G, Klingelhutz A.  Co-regulation of p16INK4A and migratory genes in culture conditions that lead to premature senescence in human keratinocytes.  J Invest Dermatol.  2005 September. 125(3):499-509.
[Link]

Ault K, Allen H, Phillips S, Zimmerman M, Klingelhutz A.  Telomerase activity as a potential diagnostic marker for triage of abnormal Pap smears.  J Low Genit Tract Dis.  2005 April. 9(2):93-9.
[Link]

Peterson M, Ault K, Kremer M, Klingelhutz A, Davis C, Squier C, Schlievert P.  The innate immune system is activated by stimulation of vaginal epithelial cells with Staphylococcus aureus and toxic shock syndrome toxin 1.  Infect Immun.  2005 April. 73(4):2164-74.
[Link]

Landen C, Klingelhutz A, Coffin J, Sorosky J, Sood A.  Genomic instability is associated with lack of telomerase activation in ovarian cancer.  Cancer Biol Ther.  2004 December. 3(12):1250-3.
[Link]

Martin J, DeYoung B, Gitelis S, Weydert J, Klingelhutz A, Kurriger G, Buckwalter J.  Telomerase reverse transcriptase subunit expression is associated with chondrosarcoma malignancy.  Clin Orthop Relat Res.  2004 September. 426:117-24.
[Link]

Plug-DeMaggio A, Sundsvold T, Wurscher M, Koop J, Klingelhutz A, McDougall J.  Telomere erosion and chromosomal instability in cells expressing the HPV oncogene 16E6.  Oncogene.  2004 April 29. 23(20):3561-71.
[Link]

Martin J, Klingelhutz A, Moussavi-Harami F, Buckwalter J.  Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence.  J Gerontol A Biol Sci Med Sci.  2004 April. 59(4):324-37.
[Link]

Luo P, Tresini M, Cristofalo V, Chen X, Saulewicz A, Gray M, Banker D, Klingelhutz A, Ohtsubo M, Takihara Y, Norwood T.  Immortalization in a normal foreskin fibroblast culture following transduction of cyclin A2 or cdk1 genes in retroviral vectors.  Exp Cell Res.  2004 April 1. 294(2):406-19.
[Link]

Lee J, Yi S, Anderson M, Berger K, Welsh M, Klingelhutz A, Ozbun M.  Propagation of infectious human papillomavirus type 16 by using an adenovirus and Cre/LoxP mechanism.  Proc Natl Acad Sci U S A.  2004 February 17. 101(7):2094-9.
[Link]

Morrison T, Mauser A, Klingelhutz A, Kenney S.  Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1.  J Virol.  2004 January. 78(1):544-9.
[Link]

Morrison J, Klingelhutz A, Raab-Traub N.  Epstein-Barr virus latent membrane protein 2A activates beta-catenin signaling in epithelial cells.  J Virol.  2003 November. 77(22):12276-84.
[Link]

Duffy C, Phillips S, Klingelhutz A.  Microarray analysis identifies differentiation-associated genes regulated by human papillomavirus type 16 E6.  Virology.  2003 September 15. 314(1):196-205.
[Link]

Palanca-Wessels M, Klingelhutz A, Reid B, Norwood T, Opheim K, Paulson T, Feng Z, Rabinovitch P.  Extended lifespan of Barrett's esophagus epithelium transduced with the human telomerase catalytic subunit: a useful in vitro model.  Carcinogenesis.  2003 July. 24(7):1183-90.
[Link]

Allen H, Klingelhutz A.  Papillomavirus infection and telomerase activation.  Papillomavirus Report.  2003 July. 14(4):155-162.

Zabner J, Karp P, Seiler M, Phillips S, Mitchell C, Saavedra M, Welsh M, Klingelhutz A.  Development of cystic fibrosis and noncystic fibrosis airway cell lines.  Am J Physiol Lung Cell Mol Physiol.  2003 May. 284(5):L844-54.
[Link]

Mauser A, Holley-Guthrie E, Zanation A, Yarborough W, Kaufmann W, Klingelhutz A, Seaman W, Kenney S.  The Epstein-Barr virus immediate-early protein BZLF1 induces expression of E2F-1 and other proteins involved in cell cycle progression in primary keratinocytes and gastric carcinoma cells.  J Virol.  2002 December. 76(24):12543-52.
[Link]

Sprague D, Phillips S, Mitchell C, Berger K, Lace M, Turek L, Klingelhutz A.  Telomerase activation in cervical keratinocytes containing stably replicating human papillomavirus type 16 episomes.  Virology.  2002 September 30. 301(2):247-54.
[Link]

Martin J, Forest E, Block J, Klingelhutz A, Whited B, Gitelis S, Wilkey A, Buckwalter J.  Malignant transformation in human chondrosarcoma cells supported by telomerase activation and tumor suppressor inactivation.  Cell Growth Differ.  2002 September. 13(9):397-407.
[Link]

Martin J, Mitchell C, Klingelhutz A, Buckwalter J.  Effects of telomerase and viral oncogene expression on the in vitro growth of human chondrocytes.  J Gerontol A Biol Sci Med Sci.  2002 February. 57(2):B48-53.
[Link]

Sood A, Coffin J, Jabbari S, Buller R, Hendrix M, Klingelhutz A.  p53 null mutations are associated with a telomerase negative phenotype in ovarian carcinoma.  Cancer Biol Ther.  2002. 1(5):511-7.
[Link]

Farwell D, Shera K, Koop J, Bonnet G, Matthews C, Reuther G, Coltrera M, McDougall J, Klingelhutz A.  Genetic and epigenetic changes in human epithelial cells immortalized by telomerase.  Am J Pathol.  2000 May. 156(5):1537-47.
[Link]

Klingelhutz A.  The roles of telomeres and telomerase in cellular immortalization and the development of cancer.  Anticancer Res.  1999 November. 19(6A):4823-30.
[Link]

Kiyono T, Foster S, Koop J, McDougall J, Galloway D, Klingelhutz A.  Both Rb/p16INK4a inactivation and telomerase activity are required to immortalize human epithelial cells.  Nature.  1998 November 5. 396(6706):84-8.
[Link]

Anderson S, Shera K, Ihle J, Billman L, Goff B, Greer B, Tamimi H, McDougall J, Klingelhutz A.  Telomerase activation in cervical cancer.  Am J Pathol.  1997 July. 151(1):25-31.
[Link]

Klingelhutz A.  Telomerase activation and cancer.  J Mol Med (Berl).  1997 January. 75(1):45-9.
[Link]

Klingelhutz A, Foster S, McDougall J.  Telomerase activation by the E6 gene product of human papillomavirus type 16.  Nature.  1996 March 7. 380(6569):79-82.
[Link]

Klingelhutz A, Hedrick L, Cho K, McDougall J.  The DCC gene suppresses the malignant phenotype of transformed human epithelial cells.  Oncogene.  1995 April 20. 10(8):1581-6.
[Link]

Klingelhutz A, Barber S, Smith P, Dyer K, McDougall J.  Restoration of telomeres in human papillomavirus-immortalized human anogenital epithelial cells.  Mol Cell Biol.  1994 February. 14(2):961-9.
[Link]

Klingelhutz A, Smith P, Garrett L, McDougall J.  Alteration of the DCC tumor-suppressor gene in tumorigenic HPV-18 immortalized human keratinocytes transformed by nitrosomethylurea.  Oncogene.  1993 January. 8(1):95-9.
[Link]

Klingelhutz A, Wu S, Huang J, Reznikoff C.  Loss of 3p13----p21.2 in tumorigenic reversion of a hybrid between isogeneic nontumorigenic and tumorigenic human uroepithelial cells.  Cancer Res.  1992 March 15. 52(6):1631-4.
[Link]

Klingelhutz A, Wu S, Reznikoff C.  Nonrandom chromosome losses in tumorigenic revertants of hybrids between isogeneic immortal and neoplastic human uroepithelial cells.  Somat Cell Mol Genet.  1991 November. 17(6):551-65.
[Link]

Klingelhutz A, Wu S, Bookland E, Reznikoff C.  Allelic 3p deletions in high-grade carcinomas after transformation in vitro of human uroepithelial cells.  Genes Chromosomes Cancer.  1991 September. 3(5):346-57.
[Link]

Wu S, Storer B, Bookland E, Klingelhutz A, Gilchrist K, Meisner L, Oyasu R, Reznikoff C.  Nonrandom chromosome losses in stepwise neoplastic transformation in vitro of human uroepithelial cells.  Cancer Res.  1991 June 15. 51(12):3323-6.
[Link]

Reznikoff C, Kao C, Bookland E, Klingelhutz A, Pratt C, Wu S, Gilchrist K, Swaminathan S.  Transformation in vitro of human uroepithelial cells.  New Jersey: Humana Press.  1991. 

Reznikoff C, Bookland E, Klingelhutz A, Pratt C, Kao C, Bhattacharya M, Swaminathan S, Meisner L.  SV-HUC-1: A human urinary tract epithelial cell line for multistep in vitro transformation studies.  England: Adam Hilger Press.  1989. 

Date Last Modified: 08/13/2014 - 14:17:19