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Microbiology & Molecular Genetics


 

Utz Herbig, Ph.D.Utz Herbig, Ph.D.
Associate Professor
Office: Cancer Center G1226
Tel: 973-972-4426
Lab: Cancer Center
Tel: 973-972-4483 x24679

Email: herbigut@njms.rutgers.edu

Herbig NJMS Profile

 

Telomere induced Senescence in Cancer and Aging

With the exception of stem cells and cells from the germ line, all human somatic cells have a limited proliferative lifespan and eventually will become senescent. Similar to apoptosis, cellular senescence has been demonstrated to function as a potent tumor suppressor mechanism, preventing the accumulation of cells that encountered signaling imbalances and other transforming events. However, as senescent cells accumulate in living organisms, they potentially contribute to organismal aging by reducing the number of functional cells in various organ systems. Although cellular senescence will likely protect us from neoplasia, it might also reduce our lifespan by contributing to biological aging of multicellular organisms.

 Our laboratory is interested in understanding how telomeres, the physical ends of linear chromosomes, contribute to senescence in mammalian cells. Telomeres consist of highly repetitive TTAGGG repeats that are associated with a large number of telomere-sequence specific and non-specicfic binding proteins. The function of telomeres is to protect the chromosome ends from nucleolytic degradation and DNA repair events in addition to serving as a buffer zone shielding genes positioned close to chromosome ends. Since linear chromosomes progressively shorten with every cell division, due to the inability of the replicative polymerase to completely duplicate linear DNA, these telomeric buffer zones therefore are critical to prevent the erosion and destruction of DNA sequences adjacent to telomeres. However, once telomeric DNA has eroded to a certain degree, telomeric structures fall apart and trigger a DNA damage response that ultimately results in growth arrest and senescence. Precisely how telomeres shorten, disassemble, and trigger senescence is currently under investigation in our lab. In addition, we are studying whether telomere induced senescence contributes to tumor suppression and organismal aging in mammals.

Selected Publications

  • Herbig, U., Ferreira, M., Condel, L., Carey, D., and Sedivy, J.M. 2006. Cellular Senescence in Aging Primates. Science 311: 1257

  • Herbig, U., and Sedivy, JM. 2006. Regulation of Growth Arrest in Senescence: Telomere Damage is Not the End of the Story. Mech. Ageing Dev. 127:16-24

  • Herbig, U., Jobling, WA., Chen, BPC, Chen, DJ., and Sedivy, JM. 2004. Telomere shortening triggers replicative senescence of human cells through a signaling pathway involving ATM, p53 and p21CIP1 but not p16INK4a. Mol. Cell 14:.501-513

  • Herbig, U., Wei, W., Dutriaux, A., Jobling WA., and Sedivy, JM. 2003. Real time imaging of transcriptional activation in live cells reveals rapid upregulation of the cyclin-dependent kinase inhibitor gene CDKN1A in replicative cellular senescence. Aging Cell 6:295-304

  • Wei W.*, Herbig, U.*, Wei, S., Dutriaux, A., Sedivy, JM. 2003. Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts. EMBO Rep. 11:1061-1066

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