Overview

NEWARK ? Utz Herbig, Ph.D., a researcher with the New Jersey Medical School-University Hospital Cancer Center, has been selected as an Ellison Medical Foundation Scholar on Aging. link to story: http://www.umdnj.edu/about/news_events/releases/07/r08

Lab Members

Utz Herbig, Ph.D.

Email: herbigut@umdnj.edu

Research: Our lab is studying whether telomere induced senescence contributes to tumor suppression and organismal aging in mammals.

Ann Dershowitz
Email: dershowi@umdnj.edu

Jessica Kaplunov
Email: fishlojm@umdnj.edu

Priyanka Patel
Email: patel216@umdnj.edu

Neetu Razdan
Email: razdanne@umdnj.edu

Education

PHD, 1999, Vanderbilt University
M.S., 1995, Ludwig-Maximilians-Universitat
B.S., 1991, Ludwig-Maximilians-Universitat

Relevant Publications

Herbig, U., Ferreira, M., Condel, L., Carey, D. and Sedivy, J.M. 2006. Cellular senescence in aging primates. Science 311:1257

Jeyapalan, JC., Ferreira, M., Sedivy, JM., and Herbig, U. 2007. Accumulation of Senescent Cells in Mitotic Tissue of Aging Primates. Mechanisms of Ageing and Development. 128:36-44

Kovalenko OA, Caron MJ, Ulema P, Medrano C, Thomas AP, Kimura M, Bonini MG, Herbig U, Santos JH. 2010. A mutant telomerase defective in nuclear-cytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction. Aging Cell. 9: 203-19.

Levy D, Neuhausen SL, Hunt SC, Kimura M, Hwang SJ, Chen W, Bis JC, Fitzpatrick AL, Smith E, Johnson AD, Gardner JP, Srinivasan SR, Schork N, Rotter JI, Herbig U, Psaty BM, Sastrasinh M, Murray SS, Vasan RS, Province MA, Glazer NL, Lu X, Cao X, Kronmal R, Mangino M, Soranzo N, Spector TD, Berenson GS, Aviv A. 2010. Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proc Natl Acad Sci U S A. 107: 9293-8.

Badie S, Escandell JM, Bouwman P, Carlos AR, Thanasoula M, Gallardo MM, Suram A, Jaco I, Benitez J, Herbig U, Blasco MA, Jonkers J, Tarsounas M. 2010. BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping. Nat Struct Mol Biol. 17 1461-9

Granick M, Kimura M, Kim S, Daniali L, Cao X, Herbig U, Aviv A. 2011. Telomere dynamics in keloids. Eplasty 11 e15

Benhamed M, Herbig U, Ye T, Dejean A, Bischof O. 2012. Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells. Nat Cell Biol. 14 266-75.

Fumagalli M, Rossiello F, Clerici M, Barozzi S, Cittaro D, Kaplunov JM, Bucci G, Dobreva M, Matti V, Beausejour CM, Herbig U, Longhese MP, d'Adda di Fagagna F. 2012. Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation. Nat Cell Biol. 14 355-65.

Suram A, Kaplunov J, Patel PL, Ruan H, Cerutti A, Boccardi V, Fumagalli M, Di Micco R, Mirani N, Lal Gurung R, Prakash Hande M, d'Adda di Fagagna F, Herbig U. 2012. Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J doi: 10.1038/emboj.2012.132.

Boccardi V, Herbig U. 2012. Telomerase gene therapy: a novel approach to combat aging. EMBO Mol Med. doi: 10.1002/emmm.201200246

Areas Of Interest

Cancer Biology

Cancer Oncology

DNA Damage

Drug Design

Immunology

Molecular Mechanisms of Cancer

Repair and Radiation Response

Signal Transduction

Therapeutics

Telomere Damage Induced Senescence and its Role in Aging and Tumor Suppression

What is Cellular Senescence?

With the exception of a few cell types, such as stem cells or germ line cells, all cultured human cells are mortal and eventually will undergo a terminal growth arrest called cellular senescence. Although senescent cells remain metabolically active for years, they are not able to re-enter the cell division cycle.

Most importantly, we would like to be able to control the growth of neoplasias. By selectively triggering a senescence growth arrest only in cells that have lost the ability to respond to the normal cellular growth programs, such as cancer cells, one could potentially block the advance of certain neoplasias. Understanding the detailed molecular mechanism of telomere dysfunction induced senescence will therefore be critical for manipulating disease outcome.

Recently we have demonstrated that senescent cells, containing damaged telomeres, accumulate in skin tissues of aging baboons. We suggested that the accumulation of senescent cells in aging animals might contribute to the functional decline of various organ systems observed in old age. If this assumption is correct, one could potentially impede the advance of aging associated diseases by manipulating the senescence program in specific tissues.