A5003954107- Cell death mechanisms and regulation
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Cancer-related Molecular Pathways
- 3D Printing in Biomedical Research
- NF-κB Signaling Pathways
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- DNA Repair Mechanisms
- Cell Adhesion Molecules Research
- Trace Elements in Health
- PARP inhibition in cancer therapy
- Cell Image Analysis Techniques
- Molecular spectroscopy and chirality
- Seaweed-derived Bioactive Compounds
- Ubiquitin and proteasome pathways
- Spinal Cord Injury Research
- Cancer therapeutics and mechanisms
- Inflammasome and immune disorders
- Protein Kinase Regulation and GTPase Signaling
- Immune Response and Inflammation
- Nuclear Structure and Function
- Immunotherapy and Immune Responses
- Enzyme Structure and Function
Ollscoil na Gaillimhe – University of Galway
2014-2025
Centre for Biomedical Engineering and Physics
2009
National University of Ireland
2007
National Institutes of Health
2001-2005
Frederick National Laboratory for Cancer Research
2001-2004
Center for Cancer Research
2004
National Cancer Institute
2001
Cold Spring Harbor Laboratory
1997-1998
MRC Toxicology Unit
1993-1995
University of Leicester
1994-1995
Abstract Apoptosis is a process in which cells die controlled manner and apparently participate their own demise. It best characterized morphologically by condensation of chromatin biochemically cleavage at internucleosomal regions to yield classical DNA ladder pattern. was induced thymocytes exposure either the glucocorticoid, dexamethasone, or topoisomerase II inhibitor, etoposide. We describe formation large m.w. fragments DNA, 30 50 kilobase pairs length, population these an early stage...
We have recently developed a method for the separation and quantification of viable apoptotic cells without need permeabilisation or fixation cells. The is based on observation that rat thymocytes fluoresce more brightly than normal after brief incubation with DNA binding dye, Hoechst 33342. In order to understand these differences, we investigated uptake 33342 by thymocytes. By staining fluorescein diacetate, shown efflux from rapid This result demonstrated an increase in permeability...
Caspases, a family of cysteine proteases most often investigated for their roles in apoptosis, have also been demonstrated to functions that are vital the efficient execution cell differentiation. One such role has described is requirement caspase-3 differentiation skeletal myoblasts into myotubes but, as yet, mechanism leading activation this case remains elusive. Here, we demonstrate caspase-9, an initiator caspase mitochondrial death pathway, responsible differentiating C2C12 cells....
Understanding how oncogenic transformation sensitizes cells to apoptosis may provide a strategy kill tumor selectively. We previously developed cell-free system that recapitulates oncogene dependent as reflected by activation of caspases, the core apoptotic machinery. Here, we show this requires identified apoptosis-promoting complex consisting caspase-9, APAF-1, and cytochrome c . As predicted in vitro system, preventing caspase-9 blocked drug-induced sensitized E1A, an adenoviral oncogene....
Apoptosis was induced in THP.1 cells, a human monocytic tumour cell line, by diverse stimuli including cycloheximide, thapsigargin, etoposide and staurosporine. Induction of apoptosis all these stimuli, except etoposide, enhanced the presence trypsin-like protease inhibitor, N alpha-tosyl-L-lysinyl chloromethyl ketone (TLCK). apoptosis, assessed morphological, flow cytometric biochemical criteria, proteolysis poly(ADP-ribose) polymerase cleavage DNA to large kilobasepair fragments,...
Apoptosis was induced in thymocytes using diverse stimuli order to identify events within a common apoptotic pathway. Benzyloxycarbonyl‐valinyl‐alaninyl‐aspartyl fluoromethyl ketone (Z‐VAD.FMK), an interleukin‐1β‐converting enzyme (ICE)‐like protease inhibitor, inhibited apoptosis assessed by flow cytometry, proteolysis of poly (ADP)‐ribose polymerase (PARP), early biochemical marker apoptosis, and cleavage DNA both large kilobase pair fragments.(30–50 200–300 kbp) nucleosomal fragments....
Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian homolog A [MIHA]) is a potent inhibitor exerts its effects, at least in part, by the direct association with inhibition specific caspases.Here, we describe molecular cloning characterization human gene related to ILP-1, termed ILP-2.Despite high homology ILP-2 encoded distinct gene, which normal tissues expressed solely testis.In contrast overexpression had no protective effect on...
MicroRNAs (miRNAs) are deregulated in cancer and have been shown to exhibit both oncogenic tumor suppressive functions. Although the functional effects of several miRNAs elucidated, those many remain be discovered. In silico analysis identified microRNA-206 (miR-206) binding sites 3'-untranslated regions (3'-UTR) mouse human CCND1 gene. Cyclin D1 is a recognized oncogene involved direct phosphorylation retinoblastoma (Rb) protein promoting cell cycle transition from G1 S. miR-206...
Abstract Caspase-2, -9, and -3 are reported to control myoblast differentiation into myotubes. This had been previously explained by phosphatidylserine exposure on apoptotic myoblasts inducing in neighboring cells. Here we show for the first time that caspase-3 is activated undergoing differentiation. Using RNAi, also demonstrate requires both cytochrome c Apaf-1, using a new pharmacological approach, apoptosome formation required. We Bid, whose cleavage links caspase-2 mitochondrial death...
The apoptosome, a critical protein complex in apoptosis regulation, relies on intricate interactions between its components, particularly the proteins containing Caspase Activation and Recruitment Domain (CARD). This work presents thorough computational analysis of stability specificity CARD-CARD within apoptosome. Departing from available crystal structures, we identify important residues for interaction CARD domains Apaf-1 Caspase-9. Our results underscore essential role these apoptosome...
Fasciola hepatica, or liver fluke, causes fasciolosis in humans and livestock. Following ingestion of vegetation contaminated with encysted parasites, metacercariae, newly excysted juveniles (NEJ) excyst the small intestine cross intestinal wall. After penetrating liver, parasite begins an intra-parenchymal migratory feeding phase that not only drives their rapid growth development but also extensive haemorrhaging immune pathology. Studies on infection are hindered by difficulty accessing...
In silico toxicity prediction offers the chance of reducing or replacing most animal testing through integration large experimental assay datasets with appropriate computational approaches. The use Cell Painting to detect various phenotypic changes induced by chemicals is emerging as a powerful technique in prediction. However, approaches cancer cells that are less relevant for many toxicological endpoints, which may limit usefulness this data. study, myoblast cell line used characterize...
Transcription factor NF-κB is persistently activated in many chronic inflammatory diseases and cancers. The short term regulation of well understood, but little known about the mechanisms its long activation. We studied effect a single application TNF-α on activity for up to 48 h intestinal epithelial cells. Results show that remained after activation was accompanied by biphasic degradation IκBα. first phase IκBα proteasome-dependent, second not. Further investigation showed stimulated...
Many genotoxic agents kill tumor cells by inducing apoptosis; hence, mutations that suppress apoptosis produce resistance to chemotherapy. Although directly activating the apoptotic machinery may bypass these mutations, how achieve this activation in cancer selectively is not clear. In study, we show drug-resistant 293 cell line unable activate components of machinery-the ICE-like proteases (caspases)-following treatment with an anticancer drug. Remarkably, extracts from untreated...
Complex networks of signaling pathways control the apoptotic response and, therefore, cell survival. However, these converge on a common machinery, which caspase cysteine proteases are key components. Diverse stimuli release holocytochrome c from mitochondria, allowing to bind protease activating factor-1 (Apaf-1), in turn binds caspase-9 both this and forming an Apaf-1/caspase-9 holoenzyme. Cytochromec lacking heme (the apo form) cannot support activation, although reason for has not been...