A5013468764- Telomeres, Telomerase, and Senescence
- Single-cell and spatial transcriptomics
- Nuclear Structure and Function
- Genetics, Aging, and Longevity in Model Organisms
- RNA Research and Splicing
- Mesenchymal stem cell research
- RNA Interference and Gene Delivery
- Cytomegalovirus and herpesvirus research
- RNA modifications and cancer
- Long-Term Effects of COVID-19
- COVID-19 Clinical Research Studies
- Microtubule and mitosis dynamics
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Angiogenesis and VEGF in Cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Circadian rhythm and melatonin
- Adipose Tissue and Metabolism
- DNA Repair Mechanisms
- Birth, Development, and Health
- Colorectal Cancer Surgical Treatments
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Molecular Biology Techniques and Applications
Rutgers, The State University of New Jersey
2019-2024
Rutgers New Jersey Medical School
2019-2023
The University of Texas Southwestern Medical Center
2017-2019
Southwestern Medical Center
2017-2019
The Ohio State University
2009-2014
Columbus Oncology and Hematology Associates
2014
Laboratory of Molecular Genetics
2009
Telomere length within an individual varies in a correlated manner across most tissues.
Abstract It is generally recognized that the function of immune system declines with increased age and one major changes impaired T‐cell responses upon antigen presentation/stimulation. Some “high‐performing” centenarians (100+ years old) are remarkably successful in escaping, or largely postponing, age‐related diseases. However, majority (“low‐performing”) have experienced these pathologies forced to reside long‐term nursing facilities. Previous studies pooled all examining heterogeneous...
tRNAs in yeast and vertebrate cells move bidirectionally reversibly between the nucleus cytoplasm. We investigated roles of members beta-importin family tRNA subcellular dynamics. Retrograde import into is dependent, directly or indirectly, upon Mtr10. nuclear export utilizes at least two family. The beta-importins involved have shared exclusive functions. Los1 functions both primary reexport processes. Msn5 unable to round if are encoded by intron-containing genes, for these primarily their...
Standard and targeted cancer therapies for late-stage patients almost universally fail due to tumor heterogeneity/plasticity intrinsic or acquired drug resistance. We used the telomerase substrate nucleoside precursor, 6-thio-2′-deoxyguanosine (6-thio-dG), target telomerase-expressing non–small cell lung cells resistant EGFR-inhibitors commonly chemotherapy combinations. Colony formation assays, human xenografts as well syngeneic genetically engineered immune competent mouse models of were...
Adults with comparatively short or long leukocyte telomere length (LTL) typically continue to display LTL throughout life. This tracking stems from the inability of person‐to‐person variation in age‐dependent shortening during adulthood offset wide interindividual established prior adult However, children is unstudied. study aimed examine rates and their parents. Longitudinal ( n = 67) parents 99), whose ages at baseline were 11.4 ± 0.3 43.4 0.4 yr, respectively. was measured by Southern...
Abstract Hutchinson–Gilford progeria syndrome (HGPS) is characterized by accelerated senescence due to a de novo mutation in the LMNA gene. The produces an abnormal lamin A protein called progerin that lacks splice site necessary remove farnesylated domain. Subsequently, accumulates nuclear envelope, disrupting architecture, chromatin organization, and gene expression. These alterations are often associated with rapid telomere erosion cellular aging. Here, we further characterize molecular...
Researchers increasingly wish to test hypotheses concerning the impact of environmental or disease exposures on telomere length (TL), and they use longitudinal study designs do so. In population studies, TL is usually measured with a quantitative polymerase chain reaction (qPCR)-based method. This method has been validated by calculating its correlation gold standard such as Southern blotting (SB) in cross-sectional data sets. However, cross-section, range true variation large, measurement...
Telomerase activity is not readily detected in resting human T lymphocytes, however upon antigen presentation, telomerase transiently upregulated. Presently, it known if activation necessary for the proliferation of cells or maintenance telomere lengths. In this study, we found that required short- term and telomeres progressively shorten a heterogeneous population cells, even detected. By measuring at single-cell level using quantitative ddPCR techniques (ddTRAP) by monitoring changes...
Abstract Telomere length (TL) limits somatic cell replication. However, the shortest among telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL epidemiological studies. SB provides little information 92 nucleus human cells. Therefore, known about accumulation short with age, or whether it lifespan. To fill this knowledge void, we used...
Abstract Background. T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic transplantation (HCT). This process may be modeled as dynamical system in such system, precise telomere length (TL) measurement reflect the proliferative capacity donor cells. TL for different chromosomes span few orders magnitude, clones will display variable TL; these differences across population are not represented when examining average TL. study aims to develop method that...
Summary Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot length (TL) 5 kilobases (kb) was estimated as the ‘telomere brink’ at which human survival is markedly reduced. However, shortest telomere, not TL, signals replicative senescence. We used Telomere Shortest Length Assay (TeSLA) to tally TL all 46 chromosomes in blood‐derived DNA examined...
Lymphocyte telomere length (TL) is highly variable and shortens with age. Short telomeres may impede TL-dependent T-cell clonal expansion viral infection. As SARS-CoV-2 infection can induce prolonged severe lymphopenia, infected adults, particularly older adults short telomeres, display lymphopenia. To examine the relationship between TL parameters counts, we studied 40 patients hospitalized COVID-19. T-cells were isolated from lymphocytes, counted using flow cytometry, their measured...
Background Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular disease. Endothelial repair plays a key role in the development of atherosclerosis. The objective was to examine associations between TL and proliferative dynamics endothelial colony‐forming cells (ECFCs), which behave as progenitor displaying activity. Methods Results To isolate ECFCs, we performed clonogenic assay on blood samples from 116 participants (aged 24–94 years) TELARTA (Telomere...
Trm1 is a tRNA specific m(2)(2)G methyltransferase shared by nuclei and mitochondria in Saccharomyces cerevisiae. In nuclei, peripherally associated with the inner nuclear membrane (INM). We investigated mechanism delivering/tethering to INM. Analyses of mutations Ran pathway pore components showed that accesses nucleoplasm via classical import pathway. identified cis-acting sequence sufficient target passenger proteins Detailed mutagenesis this region uncovered amino acids necessary for...
The age of allogeneic hematopoietic cell transplant (HCT) donors and their telomere length (TL) might affect recipients' outcomes. Our goals were to examine the possible effect these donors' factors on TL quantify shortening in critical first three-month post-HCT. We measured parameters 75 recipient-donor pairs, from Blood Marrow Transplant Clinical Trials Network (protocol#1202), by Southern blotting (SB), Telomeres Shortest Length Assay (TeSLA), quantitative PCR (qPCR). Recipients'...
Lymphopenia due to a plummeting T-cell count is major feature of severe COVID-19. proliferation telomere length (TL)-dependent and TL shortens with age. Older persons are disproportionally affected by COVID-19, we hypothesized that those short have less capacity mount an adequate proliferative response SARS-CoV-2. This hypothesis predicts among older patients shorter telomeres peripheral blood mononuclear cells (PBMCs) will be associated lower lymphocyte count. Our sample comprised 17...
Abstract Measuring telomere length (TL) with high precision is challenging. Currently there insufficient understanding of the causes variation in measurement precision, particularly for qPCR-based measurement. To better understand how DNA extraction protocols and laboratory-specific analytical factors influence TL we conducted a multi-laboratory study involving four labs six assaying same blinded human whole blood samples. differed underlying principles (magnetic beads, salting out, silica...
Appropriate targeting of inner nuclear membrane (INM) proteins is important for function and architecture. To gain new insights into the mechanism(s) and/or tethering peripherally associated to INM, we screened a collection temperature sensitive S. cerevisiae yeast mutants defects in INM location peripheral protein, Trm1-II-GFP. We uncovered numerous genes encoding components Spindle Pole Body (SPB), centrosome. SPB alterations affect localization both an integral (Heh2) protein...
Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) short LTL, infer a causal role of LTL in ASCVD. Recent results, the blood-and-muscle model, indicate that higher early life attrition, as estimated by ratio between and skeletal muscle (MTL), rather than at conception, MTL, should be responsible ASCVD-LTL connection. We combined MTL measurements SNPs profiling...
Abstract Objective: Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular disease. Endothelial repair plays a key role in the development of atherosclerosis. To explore potential short TL atherogenesis, we examined associations between and proliferative dynamics endothelial colony forming cells (ECFCs), which behave as progenitor displaying activity. Design method: isolate ECFCs, performed clonogenic assay on blood samples from 116 participants (24 to 94...