RESEARCH: Telomere Dysfunction-Induced Senescence in Aging, Cancer, and Tissue Repair

Over 60 years ago, it was reported that human somatic cells cannot proliferate indefinitely and instead undergo a stable proliferative arrest, called replicative senescence, after dividing a finite number of times. It was suggested that this limited proliferative capacity served one important purpose: to limit the growth of cancer cells. As a side effect of these tumor-suppressing properties, however, cellular senescence was also predicted to promote aging, as an inability to proliferate extensively would increasingly prevent our cells from regenerating and repairing tissue as we get older. Both predictions, however, remained untested for decades because the molecular trigger of replicative senescence was unknown. While my previous work identified dysfunctional telomeres as the molecular switch that activated replicative senescence, work in my current laboratory has provided evidence that telomere dysfunction-induced senescence (TDIS) contributes to the aging of primates, revealed that TDIS acts as a tumor-suppressing mechanism by restricting the proliferation of pre-malignant cancer cells, and demonstrated a role for telomere dysfunction in wound healing and tissue repair.

My research program currently focuses on four major areas: 1) causes of telomere shortening and dysfunction, 2) telomeres and cellular senescence in tissue repair and cell plasticity, 3) telomeres and cellular senescence in cancer development, and 4) telomeres and cellular senescence in aging.

Selected Publications

·         Turano PS, Akbulut E, Aquino NM, Garza-Martínez L, Singh S, Yap GS, Fitzgerald-Bocarsly P, Martínez-Zamudio RI, Herbig U.  Senescent CD8 T Effector Memory Cells are Functionally Impaired, Enriched in Aging and Disease, and a Barrier to Immunotherapy. 2025. bioRxiv doi: 10.64898/2025.12.16.694716.

·         Turano PS, Akbulut E, Dewald HK, Vasilopoulos T, Fitzgerald-Bocarsly P, Herbig U^*, Martínez-Zamudio RI^*. Age-independent and targetable Transcription Factor Networks regulating CD8 T cells Senescence in Aging Humans. 2026. Cell Reports, 45, 116795. *co-senior authors.

·         Ricardo Iván Martínez-Zamudio, Alketa Stefa, José Américo Nabuco, Themistoklis Vasilopoulos, Mark Simpson, Gregory Doré, Pierre-François Roux, Mark A. Galan⁷, Ravi J. Chokshi, Oliver Bischof and Utz Herbig. Escape From Oncogene-Induced Senescence is Controlled by POU2F2 and Memorized by Chromatin Scars. 2023. Cell Genomics, 3, 100293

·         Ricardo Iván Martínez-Zamudio¹, Hannah K. Dewald¹, Themistoklis Vasilopoulos, Lisa Gittens-Williams, Patricia Fitzgerald-Bocarsly², and Utz Herbig². 2021. Senescence-associated β-galactosidase reveals the abundance of senescent CD8+ T cells in aging humans. Aging Cell. e13344. ¹co-1^st authors; ²co-senior authors

·         Razdan N, Vasilopoulos T, Herbig U. 2018 Telomere dysfunction promotes transdifferentiation of human fibroblasts into myofibroblasts. Aging Cell 17:e12838. 

·         Patel, P., Suram, A., Mirani, N., Bischof, O., Herbig, U.2016 Derepression of hTERT Gene Expression Promotes Escape from Oncogene-Induced Cellular Senescence. PNAS; in press

·         Suram A, Kaplunov J, Patel PL, Ruan H, Cerutti A, Boccardi V, Fumagalli M, Di Micco R, Mirani N, Gurung RL, Hande MP, d'Adda di Fagagna F, Herbig U. 2012. Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. The EMBO Journal. 31: 2839-51

·         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. Nature Cell Biology 14: 355-65

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

Awards and Honors 

2023         New Jersey Medical School Mentoring Award

2023         Editorial Board, Aging Biology (2018-present)

2018         Editorial Board, Aging Cell (2018-2023)

2011         Member, Cancer Institute of New Jersey (2011-present)

2010         American Cancer Society Research Scholar Grant Award

2007         New Scholar Award; The Ellison Medical Foundation

2000         University Central Intramural Discovery Grant; Vanderbilt University

Education

1999 Ph.D. in Molecular Biology, Vanderbilt University, Nashville, TN

1995 Hauptdiplom (Masters of Science) in Chemistry/Biochemistry, Ludwig Maximilians University, Munich, Germany

Positions

2013-present Associate Professor, Microbiology, Biochemistry & Molecular Genetics, Rutgers Biomedical and Health Sciences, Rutgers, The State University of New Jersey

2006-2013 Assistant Professor, Microbiology & Molecular Genetics, University of Medicine and Dentistry of New Jersey (UMDNJ)