A5075500933- Telomeres, Telomerase, and Senescence
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Genetic and Kidney Cyst Diseases
- RNA Interference and Gene Delivery
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- Nuclear Structure and Function
- Genetics, Aging, and Longevity in Model Organisms
- Epigenetics and DNA Methylation
- Microplastics and Plastic Pollution
- Heat shock proteins research
- Renal cell carcinoma treatment
- Renal and related cancers
- Mesenchymal stem cell research
- Hedgehog Signaling Pathway Studies
- DNA Repair Mechanisms
- Neonatal Respiratory Health Research
- Estrogen and related hormone effects
- Protein Tyrosine Phosphatases
- DNA and Nucleic Acid Chemistry
- Pluripotent Stem Cells Research
- Cytokine Signaling Pathways and Interactions
- Animal Genetics and Reproduction
- Virus-based gene therapy research
Indiana University – Purdue University Indianapolis
2010-2023
Indiana University School of Medicine
2009-2023
Indiana University
2006-2022
Indiana University Health
2009-2017
Illinois College
2017
University of Illinois Urbana-Champaign
2017
University of Illinois Chicago
2017
Johns Hopkins University
2014
New York University
2014
Cornell University
2014
Telomere shortening is the mechanism underlying replicative aging in fibroblasts. A variety of reports now claim that inactivation p16 INK4a /pRB pathway required addition to telomere maintenance for immortalization cells such as skin keratinocytes and breast epithelial cells. We here show premature growth arrest these cell types can be explained by an inadequate culture environment. Providing mesenchymal/epithelial interactions cultivating telomerase-expressing on feeder layers avoids...
Human fibroblasts expressing the catalytic component of human telomerase (hTERT) have been followed for 250–400 population doublings. As expected, activity declined in long term culture stable transfectants. Surprisingly, however, clones with average telomere lengths several kilobases shorter than those senescent parental cells continued to proliferate. Although longest telomeres shortened, size shortest was maintained. Cells subsenescent proliferated an additional 20 doublings after...
Abstract Recent microarray studies have identified distinct subtypes of breast tumors that arise from different cell types and show statistically significant differences in patient outcome. To gain insight into these differences, we vitro vivo changes gene expression induced by chemotherapeutics. We treated two lines derived basal epithelium (immortalized human mammary epithelial cells) luminal (MCF-7 ZR-75–1) with chemotherapeutics used the treatment cancer assayed for using DNA...
Micelle-based siRNA carriers ("micelleplexes") were prepared from the A−B−C triblock copolymer poly(ethylene glycol)-poly(n-butyl acrylate)-poly(2-(dimethylamino)ethyl methacrylate) (PEG-PnBA-PDMAEMA), and their in vitro performance vivo biodistribution properties compared with benchmark PEGylated basic polycation systems PEG-PDMAEMA PDMAEMA, respectively. The micelle architecture, incorporating increased PEG shielding a larger particle size (∼50 nm) than polycation-based complexes...
Abstract Purpose: Maintenance of telomeres by telomerase is critical for the continuing proliferation most advanced cancer cells. Telomerase activity has been detected in vast majority cells but not normal cells, making enzyme an attractive target anticancer therapy. The aim this study was to address breast translational potential novel inhibitor, GRN163L. Experimental Design: In present study, we investigated effects GRN163L treatment on a panel representing different tumor subtypes with...
Abstract Telomeres are repetitive (TTAGGG)n DNA sequences found at the end of chromosomes that protect ends from recombination, to fusions, and recognition as damaged DNA. Telomerase activity can be detected in 85% 90% human tumors, which stabilizes telomeres prevent apoptosis or cellular senescence. Previous reports showed efficacy novel telomerase template antagonist, GRN163L, a potential anticancer agent. The objective present study was elucidate molecular effects GRN163L MDA-MB-231...
Abstract The asymmetric organization of epithelial cells is a basic counter to cellular proliferation. However, the mechanisms whereby pro-growth pathways are modulated by intracellular factors that control cell shape not well understood. This study demonstrates adaptor protein Amot, in addition its established role regulating asymmetry, also promotes extracellular signal-regulated kinase 1 and 2 (ERK1/2)–dependent proliferation mammary cells. Specifically, expression Amot80, but mutant...
The mechanisms underlying the dedifferentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is known whether fibroblast recapitulates generation multipotent progenitors during embryonic development, which give rise to hematopoietic cell lineages. Here we established role developmental transcription factor SOX17 in regulating bilineage by intermediate progenitors.CD34+ were generated after dermal...
Autosomal dominant polycystic kidney disease (ADPKD) causes progressive loss of renal function in adults as a consequence the accumulation cysts. ADPKD is most common genetic cause end-stage disease. Mutations polycystin-1 occur 87% cases and mutations polycystin-2 are found 12% patients. The complexity has hampered efforts to identify mechanisms underlying its pathogenesis. No current FDA (Federal Drug Administration)-approved therapies ameliorate progression. We used de Almeida...
Background: Activation of telomerase is an early event in the development breast and other cancers that may lead to cell immortalization, a critical rate-limiting step cancer progression. Breast epithelial cells from women with Li–Fraumeni syndrome (LFS) immortalize spontaneously reproducibly culture. We, therefore, tested whether immortalization these could be prevented by treating them chemopreventive agents inhibiting activity. Methods: Noncancerous, preimmortal derived patient LFS were...
Specific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment, early detection and targets chemoprevention. It has been previously demonstrated that altered mRNA proteome signatures morphologically normal cells bearing a single inherited "hit" tumor suppressor parallel many observed the corresponding sporadic cancer. Here, we report on global profile normal, cultured primary breast epithelial stromal from Li-Fraumeni syndrome (LFS)...
Telomerase is one of the key enzymes responsible for proliferative immortality majority cancer cells. We recently introduced a new telomerase inhibitor, 13-mer oligonucleotide N3' --> P5'-thio-phosphoramidate lipid conjugate, designated as GRN163L. This compound inhibits activity in various tumor cell lines with IC(50) values 3-300 nM without any cellular uptake enhancers. GRN163L demonstrated potent and sequence specific anti-cancer vivo multiple animal models. was able to significantly...
Excess telomere shortening has been observed in most cancer cells. The quantitative polymerase chain reaction (qPCR) assay become an important tool for epidemiological studies examining the effects of aging, stress, and other factors on length telomeres. Current qPCR methods analyze relative telomeres by amplifying sequence products normalizing with single-copy gene products. However, current does not always reflect absolute DNA. Because genomic instability cells, we hypothesized that use...
The aryl hydrocarbon receptor (AhR), a client protein of heat shock 90 (Hsp90), is ligand-activated transcription factor that plays role in polycyclic aromatic (PAH)-induced carcinogenesis. Tobacco smoke activates AhR signaling leading to increased CYP1A1 and CYP1B1, which encode proteins convert PAHs mutagens. Recently, p53 was found regulate Hsp90 ATPase activity via effects on activator (Aha1). It possible, therefore, AhR-dependent expression CYP1B1 might be affected by status. main...