Faculty, Kellogg School of Science and Technology
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.
B.S., Chemistry, Duke University, Durham, NC, 1985
M.S., Physiology, Georgetown University School of Medicine, Washington, D.C., 1990
Ph.D., Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, 1996
M.D., Pathology, Vanderbilt University School of Medicine, Nashville, TN, 1998
1982 – 1984: Department of Neurooncology, Research Assistant, Duke University, Durham, NC
1985 – 1989: Department of Toxicology, Research Assistant, Massachusetts Institute of Technology, Cambridge, MA
2003 – 2009: Department of Microbiology and Molecular Genetics, Assistant Professor, University of Pittsburgh School of Medicine; Molecular and Cellular Biology Program, University of Pittsburgh Cancer Institute
2009 – 2012: Department of Microbiology and Molecular Genetics, Associate Professor, University of Pittsburgh School of Medicine; Molecular and Cellular Biology Program, University of Pittsburgh Cancer Institute
2012 – Present: Department of Metabolism and Aging, Associate Professor, The Scripps Research Institute, Jupiter, FL
June 1992 – May 1994: Medical Scientist Training Program Traineeship, NIH
June 1994 – May 1996: Predoctoral Traineeship on the Breast Cancer Training Grant, DOD
1998: Elected to Sigma Xi
June 1999 – Jan. 2000: National Science Foundation International Research Fellow Award
Jan. 2000 – Dec. 2002: American Cancer Society Post-doctoral fellowship
2005: PNC Foundation Innovation Award
2005 – 2006: Hillman Foundation Fellow
2005 – 2009: Ellison Medical Foundation New Scholar in Aging
2007 – 2012: Outstanding New Environmental Scientist, NIEHS
2008: Elected to the American Society for Clinical Investigation
2009: Hillman Fellow for Innovative Cancer Research
2010: Chancellor's Distinguished Research Award
2003 - Present: DNA Repair
2009 - Present: Pitt Med Magazine
2010 - Present: Associate Editor: DNA Repair
2005 – 2009: FASEB Summer Research Conferences Committee
2006 – Present: Xeroderma pigmentosum Society Scientific Advisor
2006 – Present: Xeroderma pigmentosum Family Support Group Scientific Advisor
2009 – Present: FASEB Board of Directors
2009 – 2010: Environmental Mutagen Society Program Committee
2009 – Present: FASEB Peer Review Committee
2010 – Present: FASEB Public Affairs Committee
2004 – Present: Volunteer Camp Sundown for children with xeroderma pigmentosum
Zhu, X.-D., Niedernhofer, L.J., Kuster, B., Mann, M., Hoeijmakers, J.H.J. and de Lange, T. (2003) ERCC1/XPF removes the 3' overhang from uncapped telomeres and represses formation of telomeric DNA containing double minute chromosomes. Mol Cell, 12(6):1489-98.
Niedernhofer, L.J., Odijk, H., Budzowska, M., van Drunen, E., Maas, A., Theil, A.F., de Wit, J., Jaspers, N.G.J., Beverloo, H.B., Hoeijmakers, J.H.J. and Kanaar, R. (2004) The structure-specific endonuclease Ercc1-Xpf is required to resolve DNA interstrand cross-link-induced double-strand breaks. Mol Cell Biol, 24(13):5776-87.
Niedernhofer, L.J., Garinis, G.A., Raams, A., Lalai, A.S., Robinson, A.R., Appeldoorn, E., Lalai, A., Odijk, H., Oostendorp, R., Ahmad, A., van Leeuwen, W., Theil, A.F., van der Horst, G.T.J., Vermeulen, W., Meinecke, P., Kleijer, W.J., Vijg, J., Jaspers, N.G.J., and J.H.J. Hoeijmakers (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature, 444(7122):1038-43.
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
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
Vaezi, A., Wang, X-Z, Buch, S., Gooding, W., Wang, L., Seethala, R.R., Weaver, D.T., D'Andrea, A., 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.
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.
DeLoia, J.A., Bhagwat, N.R., Darcy, K.M., Strange. M., Tian C., Nuttall, K., Niedernhofer, L.J., and T. Krivak (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
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., Beer Stolz, D., 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
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.*, 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.
Smith, S.C., Robinson, A.R., Niedernhofer, L.J. and M. Hetman (2012) Down-regulation of cholesterol biosynthesis genes in the forebrain of ERCC1-deficient mice. Neurobiol Dis., 45(3):1136-44. PMC3345809
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.
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
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
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., 8:817-22. PMC3509257