A5102920475- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- PARP inhibition in cancer therapy
- Bladder and Urothelial Cancer Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Cancer Immunotherapy and Biomarkers
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Chromatin Remodeling and Cancer
- Urinary and Genital Oncology Studies
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- Pluripotent Stem Cells Research
- Advanced biosensing and bioanalysis techniques
- Chromosomal and Genetic Variations
- Sirtuins and Resveratrol in Medicine
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Coordination Chemistry and Organometallics
- Asymmetric Synthesis and Catalysis
- Immunotherapy and Immune Responses
- Renal and related cancers
- Animal Virus Infections Studies
- Melanoma and MAPK Pathways
- Cancer Research and Treatments
Merck & Co., Inc., Rahway, NJ, USA (United States)
2019-2025
Sidney Kimmel Comprehensive Cancer Center
2012-2020
GlaxoSmithKline (United States)
2019-2020
Johns Hopkins University
2012-2019
Johns Hopkins Medicine
2015-2019
Providence College
2019
Sidney Kimmel Cancer Center
2010-2013
University of Castilla-La Mancha
2006-2011
Amsterdam UMC Location University of Amsterdam
2011
Harvard University
2005-2009
Telomere shortening limits the number of cell divisions primary human cells and might affect regenerative capacity organ systems during aging chronic disease. To test whether telomere hypothesis applies to cirrhosis, length was monitored in cirrhosis induced by a broad variety different etiologies. Telomeres were significantly shorter compared with noncirrhotic samples independent etiology age patients. Quantitative fluorescence situ hybridization showed that restricted hepatocytes whereas...
Immunoglobulin (Ig) isotype switching is a recombination event that changes the constant domain of antibody genes and catalyzed by activation-induced cytidine deaminase (AID). Upon recruitment to Ig genes, AID deaminates cytidines at switch (S) sites, leading formation DNA breaks. In addition their role in switching, AID-induced lesions promote Igh-cMyc chromosomal translocations tumor development. However, cMyc are also present lymphocytes from healthy humans mice, thus, it remains unclear...
Somatic inactivating mutations in ARID1A, a component of the SWI/SNF chromatin remodeling complex, are detected various types human malignancies. Loss ARID1A compromises DNA damage repair. The induced burden may increase reliance on PARP-dependent repair cancer cells to maintain genome integrity and render susceptibility PARP inhibitor therapy.Experimental Design: Isogenic ARID1A-/- wild-type cell lines were used for assessing response, compactness, profiling global serine/threonine...
Telomere shortening can lead to chromosome instability, replicative senescence, and apoptosis in both somatic male germ cells. To study roles for mammalian telomeres homologous pairing recombination, we characterized effects of telomere on spermatogenesis oogenesis late-generation telomerase-deficient mice. We show that shortened mice impair meiotic synapsis decrease particular, females. In response shortening, cells mostly undergo apoptosis, whereas female preferentially arrest early...
Chromosome integrity is essential for cell viability and, therefore, highly proliferative types require active telomere elongation mechanisms to grow indefinitely. Consistently, deletion of telomerase activity in a genetically modified mouse strain results growth impairments all populations analyzed so far. We show that attrition dramatically impairs the vitro proliferation adult neural stem cells (NSCs) isolated from subventricular zone (SVZ) telomerase-deficient mice. Reduced postnatal...
The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Artemis are classical nonhomologous DNA end-joining (C-NHEJ) factors required for joining a subset of double-strand breaks (DSB), particularly those requiring end processing. In mature B cells, activation-induced cytidine deaminase (AID) initiates class switch recombination (CSR) by introducing lesions into S regions upstream two recombining C(H) exons, which processed DSBs rejoined C-NHEJ to complete CSR. function DNA-PKcs in...
Polζ is an error-prone DNA polymerase that critical for embryonic development and maintenance of genome stability. To analyze its suggested role in somatic hypermutation (SHM) possible contribution to double-strand break (DSB) repair class switch recombination (CSR), we ablated Rev3, the catalytic subunit Polζ, selectively mature B cells vivo. The frequency mutation was reduced mutant but pattern SHM unaffected. Rev3-deficient also exhibited pronounced chromosomal instability impaired...
By imposing a replicative defect in most somatic cells, gradual telomere attrition during aging is thought to progressively impair cellular function and viability may contribute age-related disease.Immune cells play important roles all phases of atherosclerosis, multifactorial disease that prevails within the elderly.Because shorter telomeres have been found circulating blood leukocytes human patients with advanced coronary it has suggested shortening predispose organism atheroma...