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Niedernhofer Lab

My research career has been dedicated to investigating the impact of DNA damage on the structure of DNA, cell function and organism health. The DNA in each of our cells is damaged thousands of times per day by exposure to environmental factors, dietary components, chemotherapeutic agents and even endogenous by-products of normal metabolism. Studying patients with rare diseases caused by inherited defects in DNA repair provides important insight into the consequences of DNA damage. These patients have a dramatically increased risk of cancer and age prematurely. We engineered mouse models of these genome instability syndromes as a sensitive tool to test hypotheses about how DNA damage promotes cancer and aging.


Our current research program at Scripps Florida focuses on (1) discovering the mechanism by which endogenous and environmental genotoxic stress promotes aging and age-related degenerative diseases; (2) identifying the mechanism by which cancer chemotherapeutic agents, including cisplatin, stop tumor growth with the goal of improving outcomes in patients with solid tumors; and (3) determining if changes in the capacity to repair DNA contributes to cancer risk, cancer recurrence after therapy, and/or human lifespan/healthspan.

Lab Members:

Matt Yousefzadeh



B.S., Biology- College of Charleston, 2005

M.S., Cytology and Bioscience-Medical University of South Carolina, 2008

Ph.D., Biomedical Research- University of Texas MD Anderson Cancer Center, 2014

Rajesh Vyas



M.S., Biotechnology- Bundelkhand University, India, 2006

Ph.D., Biomedical Sciences- KU Leuven, Belgium, 2013

Luise Angelini



LATG- Laboratory Animal Technologist Certification-American Associate for Laboratory Animal Science, 2014

Equivalency of Bachelor in Animal Science, Study of Veterinary Medicine-University of Leipzig, Germany, 2010

Ryan O'Kelly


Collin McGuckian



B.S., Health Science- University of Flordia, 2015



Sara McGowan





Ahmad, A., Robinson, A.R., Duensing, A., van Drunen, E., Beverloo, H.B., Weisberg, D.B., Hasty, P., Hoeijmakers, J.H.J. and L.J. Niedernhofer (2008) ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Mol Cell Biol.28(16):5082-92. PMC2519706. PubMed Link

Schumacher, B., van der Pluijm, I, Moorhouse. M.J., Kosteas, T., Robinson, A.R., Suh, Y., Breit, T.M., van Steeg, H., Niedernhofer, L.J., van Ijcken, W., Bartke, A., Spindler, S.R., Hoeijmakers, J.H.J., van der Horst, G.J. and G.A. Garinis (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet., 4(8):e1000161. PMC2493043 PubMed Link


Bhagwat, N.R., Olsen, A.L., Wang A.T., Hanada, K., Stuckert, P., Kanaar, R, D'Andrea, A., Niedernhofer, L.J.* and P.J. McHugh* (2009) XPF-ERCC1 participates in the Fanconi anemia pathway of crosslink repair. Mol Cell Biol., 29(24):6427-37. PMC2786876 *co-corresponding authors. PubMed Link

Bhagwat, N.R., Roginskaya, V.Y., Acquafondata, M.D., Dhir, R., Wood, R.D. and L.J. Niedernhofer (2009) Immunodetection of DNA repair endonuclease ERCC1-XPF in human tissue. Cancer Res., 69(17): 6831-8. PMC2739111 PubMed Link


Ahmad, A., Enzlin, J.H., Bhagwat, N.R., Wijgers, N., Raams, A., Appledoorn, E., Theil, A.F., Hoeijmakers, J.H., Vermeulen, W., Jaspers, N.G., Scharer, O.D*. and L.J. Niedernhofer* (2010) Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients. PLoS Genet., 6(3):e1000871 PMC2832669 *co-corresponding authors. PubMed Link

Hagelstrom, R.T., Blagoev, K.B., Niedernhofer, L.J., Goodwin, E.H., and S.M. Bailey (2010) Hyper- telomere recombination accelerates replicative senescence and may promote premature aging. Proc Natl Acad Sci.107(36):15768-73. PMC2936608 PubMed Link

Orelli, B., McClendon, T.B., Tsodikov, O.V., Ellenberger, T., Niedernhofer, L.J. and O.D. Scharer (2010) The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways. J Biol Chem.285(6):3705-12. PMC2823511 PubMed Link

Vo, N., Seo, H.-Y., Robinson, A., Sowa, G., Bentley, D., Taylor, L., Studer, R., Usas, A., Huard, J., Alber, S., Watkins, S.C., Lee, J., Coehlo, P., Wang, D., Loppini, M., Robbins, P.D., Niedernhofer, L.J., and J. Kang (2010) Accelerated aging of intervertebral discs in a mouse model of progeria. J Orthop Res., 28(12):1600-7. PMC3477798 PubMed Link


Choi, S., Wang, W., Ribeiro, A.J., Kalinowski, A., Gregg, S.Q., Opresko, P.L., Niedernhofer, L.J., Rohde, G.K. and K.N. Dahl (2011) Computational image analysis of nuclear morphology associated with various nuclear-specific aging disorders. Nucleus, 2(6):570-9. PMC3324345 PubMed Link

Dolle, M.E.T., Kuiper, R.V., Roodbergen, M., Robinson, J., de Vlugt, S., Wijnhoven, S.W.P., Beems, D., de la Fonteyne, L., de With, P., van der Pluijm, I., Niedernhofer, L.J., Hasty, P., Vijg, J., Hoeijmakers, J.H.J., and H., van Steeg (2011) Broad segmental progeroid changes in short lived Ercc1-/Δ7 mice. Pathobiol Aging Age Rel Dis., 2011;1. PMC3417667 PubMed Link

Goss, J.R.*, Stolz, D.B., Robinson, A.R., Zhang, M., Arbujas, N., Robbins, P.D., Glorioso, J.C. and L.J. Niedernhofer* (2011) Premature aging-related peripheral neuropathy in a mouse model of progeria. Mech Ageing Dev.132(8-9):437-42. PMC3179831 *co-corresponding authors. PubMed Link

Vaezi, A., Wang, X., Buch, S., Gooding, W., Wang, L., Seethala, R.R., Weaver, D.T., D’Andrea, A.D., Argiris, A., Romkes, M., Niedernhofer, L.J.* and J.R. Grandis* (2011) XPF expression correlates with clinical outcome in squamous cell carcinoma of the head and neck. Clin Cancer Res., 17(16):5513-22. PMC3156890 *co-corresponding authors. PubMed Link

Wang, D., Vo, N.V., Sowa, G.A., Hartman, R.A., Ngo, K., Choe, S.R., Witt, W.T., Dong, Q., Lee, J.Y., Niedernhofer, L.J. and J.D. Kang (2011) Bupivacaine decreases cell viability and matrix protein synthesis in an intervertebral disc organ model system. Spine J. 11(2):139-46. PMC3056334 PubMed Link


Cho, J.S., Kook, S.H., Robinson, A.R., Niedernhofer, L.J.* and B.C. Lee*. (2012) Cell autonomous and non-autonomous mechanisms drive hematopoietic stem/progenitor cell loss in the absence of DNA repair. Stem Cells, 31(3):511-25. PMC3582850. *co-corresponding authors. PubMed Link

DeLoia, J.A., Bhagwat, N.R., Darcy, K.M., Strange. M., Tian C., Nuttall, K., Krivak, T. and L.J. Niedernhofer (2012) Comparison of ERCC1/XPF genetic variation, mRNA and protein levels in women with advanced stage ovarian cancer treated with intraperitoneal platinum. Gynecol Oncol. 126(3):448-54. PMC3518863 PubMed Link

Gregg, S.Q., Gutierrez, V., Robinson, A.R., Woodell, T., Nakao, A., Ross, M.A., Michalopolous, G.K., Rigatti, L., Rothermel, C.E., Kamileri, I., Garinis, G.A., Stolz, D.B., and L.J. Niedernhofer (2012) A mouse model of accelerated liver aging caused by a defect in DNA repair. Hepatology, 55(2):609-21. PMC3250572 PubMed Link

Lavasani, M., Robinson, A.R., Lu, A., Song, M., Feduska, J.M., Ahani, B., Tilstra, J.S., Feldman, C.H., Robbins, P.D., Niedernhofer, L.J.*, and J. Huard* (2012) Muscle-derived stem cell/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun., 3:608. PMC3272577 *co-corresponding authors. PubMed Link

Lu, A., Proto, J.D., Guo, L., Tang, Y., Lavasani, M., Tilstra, J.S., Niedernhofer, L.J., Wang, B., Guttridge, D.C., Robbins, P.D. and J. Huard (2012) NF-kB negatively impacts the myogenic potential of muscle-derived stem cells. Mol Ther., 20(3):661-8. PMC3293604 PubMed Link

Matoka D.J., Yao, V., Harya D.S., Gregg, J.L., Robinson, A.R., Niedernhofer L.J., Parwani, A.V., Maier, C., and D.J. Bacich (2012) Deficiency of DNA repair nuclease ERCC1-XPF promotes prostate cancer progression in a tissue recombination model. Prostate. 72(11): 1214-22. PMC3490419 PubMed Link

Nasto, L.A., Seo, H.-Y., Robinson, A.R., Tilstra, J.S., Clauson, C.L., Sowa, G.A., Ngo, K., Dong, Q., Pola, E., Lee, J.Y., Niedernhofer, L.J., Kang, J.D., Robbins, P.D. and N.V. Vo (2012) Inhibition of NF-kB activity ameliorates age-associated disc degeneration in a mouse model of accelerated aging. Spine, 37(21):1819-25. PMC3395770 *awarded best biology manuscript by the International Society for the Study of the Lumbar Spine (ISSLS) PubMed Link

Rubatt, J.M., Darcy, K.M., Tian, C., Muggia, F., Dhir, R., Armstrong, D.K., Bookman, M.A., Niedernhofer, L.J., Deloia, J., Birrer, M., and T.C. Krivak (2012) Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: A Gynecologic Oncology Group study. Gynecol Oncol., 125(2):421-6. PMC3490188 PubMed Link

Smith, S.C., Robinson, A.R., Niedernhofer, L.J. and M. Hetman (2012) Downregulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice. Neurobiol Dis.45(3):1136-44. PMC3345809 PubMed Link

Su, Y., Orelli, B., Madireddy, A., Niedernhofer, L.J. and O.D. Scharer (2012) Multiple DNA binding domains mediate the function of the ERCC1-XPF protein in nucleotide excision repair. J Biol Chem., 287(26):21846-55. PMC3381147 PubMed Link

Tilstra, J.S.*, Robinson, A.R.*, Wang, J.*, Gregg, S.Q.*, Clauson, C.L.*, Reay, D.P., Nasto, L.A., St. Croix, C.M., Usas, A., Vo, N., Huard, J., Clemens, P.R., Stoltz, D.B., Gutteridge, D.C., Watkins, S.C., Garinis, G.A., Wang, Y., Niedernhofer, L.J.*#, and P.D. Robbins# (2012) NF-kB inhibition delays DNA damage-induced senescence and aging in mice. J Clin Invest., 122(7):2601-12. *equal contributors, #co-corresponding authors. PMC3386805. PubMed Link

Wang, D., Nasto, L.A., Roughley, P., Leme, A.S., Houghton, A.M., Usas, A., Sowa, G., Lee, J., Niedernhofer, L.J., Shapiro, S., Kang, J. and N. Vo (2012) Spine degeneration in a murine model of chronic human tobacco smokers. Osteoarthritis Cartilage, 20(8):896-905. PMC3389285 PubMed Link

Wang, J., Cao, H., You, C., Yuan, B., Bahde, R., Gupta, S., Nishigori, C., Niedernhofer, L.J., Brooks, P.J., and Y. Wang (2012) Endogenous formation and repair of oxidatively induced G[8-5m]T intrastrand cross-link lesion. Nucleic Acids Res., 40(15):7368-74. PMC3424544 PubMed Link

Wang, J., Clauson, C.L., Robbins, P.D., Niedernhofer, L.J.* and Y. Wang* (2012) The oxidative DNA lesions 8,5'-cyclopurines accumulate with aging in a tissue-specific manner. Aging Cell, 11(4):714-6. PMC3399950 *co-corresponding authors PubMed Link

Xun, Z., Rivera-Sanchez, S., Ayala-Pena, S., Lim, J., Budworth, H., Koda, E.M., Robbins, P.D., Niedernhofer, L.J., Wipf, P. and C.T. McMurray. (2012) Targeting of XJB-5-131 to mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington's disease. Cell Rep., 2(5):1137-42. PMC3513647 PubMed Link

You, C., Dai, X., Yuan, B., Wang, J., Wang, J., Brooks, P.J., Niedernhofer, L.J. and Y. Wang (2012) A quantitative assay for assessing the effects of DNA lesions on transcription. Nat Chem Biol., 8(10):817-22.  PMC3509257 PubMed Link

NF-κB inhibition delays DNA damage-induced senescence and aging in mice. Tilstra JS, Robinson AR, Wang J, Gregg SQ, Clauson CL, Reay DP, Nasto LA, St Croix CM, Usas A, Vo N, Huard J, Clemens PR, Stolz DB, Guttridge DC, Watkins SC, Garinis GA, Wang Y, Niedernhofer LJ, Robbins PD. J Clin Invest. 2012 Jul;122(7):2601-12. doi: 10.1172/JCI45785. Epub 2012 Jun 18. PMID: 22706308 PubMed Link


Chen, Q., Liu, K., Robinson, A.R., Clauson, C.L., Blair, H.C. Robbins, P.D., Niedernhofer, L.J. and H. Ouyang (2013) DNA damage drives accelerated bone aging via an NF-kB-dependent mechanism. J Bone Miner Res., 28(5):1214-28. PMC3662975. PubMed Link

Lavasani, M., Lu, A., Thompson, S.D., Robbins, P.D., Huard, J., and L.J. Niedernhofer (2013) “Isolation of muscle-derived stem/progenitor cells based on adhesion characteristics to collagen-coated surfaces” in Methods in Molecular Biology ed. K. Turksen, Springer, 2013;976:53-65. Doi: 10.1007/978-1-62703-317-6_5. PMID: 23400434, NIHMS491012 PubMed Link

Nasto, L.A., Robinson, A.R., Ngo, K., Clauson, C.L., Dong, Q., St. Croix, C., Sowa, G., Pola, E., Robbins, P.D., Kang, J., Niedernhofer, L.J.*, Wipf, P.* and N.V. Vo.* (2013) Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration. J Orthop Res., 31(7):1150-7. PMC3668354 *co-corresponding authors.  PubMed Link

Nasto, L.A., Wang, D., Robinson, A.R., Clauson, C.L., Ngo, K., Dong, Q., Roughley, P., Epperly, M., Huq, S.M., Pola, E., Sowa, G., Robbins, P.D., Kang, J., Niedernhofer, L.J.*, Vo, N.V.* (2013) Genotoxic stress accelerates age-associated degenerative changes in intervertebral discs. Mech Ageing Dev., 134(1-2):35-42. PMC3558562. *co-corresponding authors. PubMed Link

Vo, N., Niedernhofer, L.J., Nasto, L.A., Jacobs, L., Robbins, P.D., Kang, J. and C.H. Evans (2013) An overview of underlying causes and animal models for the study of age-related degenerative disorders of the spine and synovial joints. J Orthop Res., 2013 Jun; 31(6):831-7. PMC3628921. PubMed Link

Advances in understanding the complex mechanisms of DNA interstrand cross-link repair. Clauson C, Schärer OD, Niedernhofer L. Cold Spring Harb Perspect Biol. 2013 Oct 1;5(10):a012732. doi: 10.1101/cshperspect.a012732. Review. PMID: 24086043 PubMed Link

DNA damage triggers a chronic autoinflammatory response, leading to fat depletion in NER progeria. Karakasilioti I, Kamileri I, Chatzinikolaou G, Kosteas T, Vergadi E, Robinson AR, Tsamardinos I, Rozgaja TA, Siakouli S, Tsatsanis C, Niedernhofer LJ, Garinis GA. Cell Metab. 2013 Sep 3;18(3):403-15. doi: 10.1016/j.cmet.2013.08.011. PMID: 24011075 PubMed Link

Age-related dystrophic changes in corneal endothelium from DNA repair-deficient mice. Roh DS, Du Y, Gabriele ML, Robinson AR, Niedernhofer LJ, Funderburgh JL. Aging Cell. 2013 Dec;12(6):1122-31. doi: 10.1111/acel.12143. Epub 2013 Sep 1. PMID: 23927039 PubMed Link

Isolation of muscle-derived stem/progenitor cells based on adhesion characteristics to collagen-coated surfaces. Lavasani M, Lu A, Thompson SD, Robbins PD, Huard J, Niedernhofer LJ. Methods Mol Biol. 2013;976:53-65. doi: 10.1007/978-1-62703-317-6_5. PMID: 23400434 PubMed Link

Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration. Nasto LA, Robinson AR, Ngo K, Clauson CL, Dong Q, St Croix C, Sowa G, Pola E, Robbins PD, Kang J, Niedernhofer LJ, Wipf P, Vo NV. J Orthop Res. 2013 Jul;31(7):1150-7. doi: 10.1002/jor.22320. Epub 2013 Feb 6. PMID: 23389888 PubMed Link

DNA damage drives accelerated bone aging via an NF-κB-dependent mechanism. Chen Q, Liu K, Robinson AR, Clauson CL, Blair HC, Robbins PD, Niedernhofer LJ, Ouyang H. J Bone Miner Res. 2013 May;28(5):1214-28. doi: 10.1002/jbmr.1851. PMID: 23281008 PubMed Link

Cell autonomous and nonautonomous mechanisms drive hematopoietic stem/progenitor cell loss in the absence of DNA repair. Cho JS, Kook SH, Robinson AR, Niedernhofer LJ, Lee BC. Stem Cells. 2013 Mar;31(3):511-25. doi: 10.1002/stem.1261. PMID: 23097336 PubMed Link


The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, Roos CM, Verzosa GC, LeBrasseur NK, Wren JD, Farr JN, Khosla S, Stout MB, McGowan SJ, Fuhrmann-Stroissnigg H, Gurkar AU, Zhao J, Colangelo D, Dorronsoro A, Ling YY, Barghouthy AS, Navarro DC, Sano T, Robbins PD, Niedernhofer LJ, Kirkland JL. Aging Cell. 2015 Aug;14(4):644-58. doi: 10.1111/acel.12344. Epub 2015 Apr 22. PMID: 25754370 PubMed Link

NF-κB activation with aging: characterization and therapeutic inhibition. Zhao J, Li X, McGowan S, Niedernhofer LJ, Robbins PD. Methods Mol Biol. 2015;1280:543-57. doi: 10.1007/978-1-4939-2422-6_32. PMID: 25736771 PubMed Link

Comparison of mice with accelerated aging caused by distinct mechanisms. Gurkar AU, Niedernhofer LJ. Exp Gerontol. 2015 Aug;68:43-50. doi: 10.1016/j.exger.2015.01.045. Epub 2015 Jan 21. Review. PMID: 25617508 PubMed Link


Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage. Yu Y, Cui Y, Niedernhofer LJ, Wang Y. Chem Res Toxicol. 2016 Dec 19;29(12):2008-2039. Epub 2016 Nov 7. Review. PMID: 27989142 PubMed Link

Molecular pathology endpoints useful for aging studies. Niedernhofer LJ, Kirkland JL, Ladiges W. Ageing Res Rev. 2017 May;35:241-249. doi: 10.1016/j.arr.2016.09.012. Epub 2016 Oct 6. Review. PMID: 27721062 PubMed Link

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms. Burd CE, Gill MS, Niedernhofer LJ, Robbins PD, Austad SN, Barzilai N, Kirkland JL. J Gerontol A Biol Sci Med Sci. 2016 Nov;71(11):1388-1394. Epub 2016 Aug 16. PMID: 27535964 PubMed Link

Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, Pirtskhalava T, Giorgadze N, Johnson KO, Giles CB, Wren JD, Niedernhofer LJ, Robbins PD, Kirkland JL. Aging Cell. 2016 Jun;15(3):428-35. doi: 10.1111/acel.12445. Epub 2016 Mar 18. PMID: 26711051 PubMed Link


New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Zhu Y, Doornebal EJ, Pirtskhalava T, Giorgadze N, Wentworth M, Fuhrmann-Stroissnigg H, Niedernhofer LJ, Robbins PD, Tchkonia T, Kirkland JL. Aging (Albany NY). 2017 Mar 8;9(3):955-963. doi: 10.18632/aging.101202. PMID: 28273655 PubMed Link

Quantitative Analysis of Cellular Senescence in Culture and In Vivo. Zhao J, Fuhrmann-Stroissnigg H, Gurkar AU, Flores RR, Dorronsoro A, Stolz DB, St Croix CM, Niedernhofer LJ, Robbins PD. Curr Protoc Cytom. 2017 Jan 5;79:9.51.1-9.51.25. doi: 10.1002/cpcy.16. PMID: 28055114 PubMed Link