University of Pittsburgh Department of Cell Biology

  • Research

    Genomic DNA is damaged tens of thousands of times per day in every cell. This damage occurs as a consequence of environmental insults and because electrophilic genotoxins are generated endogenously as by-products of metabolism. Maintaining the integrity of the genetic code is essential for the viability and proper functioning of cells. The fact that DNA repair mechanisms are amongst the most evolutionarily conserved of pathways also testifies to the importance of genome maintenance. Genetic diseases in which DNA repair mechanisms are affected reveal the biological consequences of DNA damage. We identified a single gene (XPF) that when mutated in humans can lead to a profound risk of cancer or rapidly accelerated aging. We modeled this in the mouse to create an experimental system in which study the relationship between DNA damage, cancer and aging.

  • Publications

    1. Niedernhofer LJ, Robbins PD. Signaling mechanisms involved in the response to genotoxic stress and regulating lifespan. Int J Biochem Cell Biol. 2008;40(2):176-80. Epub 2007 Oct 13.
    2. Niedernhofer LJ. DNA repair is crucial for maintaining hematopoietic stem cell function. DNA Repair (Amst). 2008 Mar 1;7(3):523-9. Epub 2008 Jan 8.
    3. Niedernhofer LJ. Nucleotide excision repair deficient mouse models and neurological disease. DNA Repair (Amst). 2008 Feb 11; [Epub ahead of print]
    4. Niedernhofer LJ, Bhagwat N, Wood RD. No ERCC1 and non-small-cell lung cancer. N Engl J Med. 2007 Jun 14;356(24):2538-40; author reply 2540-1.
    5. Niedernhofer LJ. The Fanconi anemia signalosome anchor. Mol Cell. 2007 Feb 23;25(4):487-90.
    6. van der Pluijm I, Garinis GA, Brandt RM, Gorgels TG, Wijnhoven SW, Diderich KE, de Wit J, Mitchell JR, van Oostrom C, Beems R, Niedernhofer LJ, Velasco S, Friedberg EC, Tanaka K, van Steeg H, Hoeijmakers JH, van der Horst GT. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome. PLoS Biol. 2007 Jan;5(1):e2.

     

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