Browsing by Author "Samali, Afshin"
Now showing items 1-20 of 65
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Antioxidant-mediated inhibition of the heat shock response leads to apoptosis
Gorman, Adrienne M.; Heavey, Barry; Creagh, Emma; Cotter, Thomas G; Samali, Afshin (Wiley-Blackwell, 1999-02-19) -
Bcl-2 family on guard at the ER
Samali, Afshin; Sanjeev, Gupta; Ní Chonghaile, Tríona; MacDonald, David C; Szegezdi, Eva (American Physiological Society, 2009)The endoplasmic reticulum (ER) is the main site for protein folding, lipid biosynthesis and calcium storage in the cell. Disturbances of these critical cellular functions lead to ER stress. The ER responds to disturbances ... -
A biological and pharmacological investigation of the unfolded protein response in models of breast cancer
Leuzzi, Brian (NUI Galway, 2020-11-20)Breast cancer is the most common malignancy in women worldwide. At the molecular level, breast cancer is a heterogeneous disease. For example, the claudin low subtype of breast cancer is characterised by epithelial-mesenchymal ... -
Cd95-mediated alteration in hsp70 levels is dependent on protein stabilization
Concannon, Caoimhín G.; FitzGerald, Una; Holmberg, Carina I.; Szegezdi, Eva; Sistonen, Lea; Samali, Afshin (Springer Nature, 2005-01-01)Engagement of death receptors induces caspase activation and apoptosis. A recent study reported altered protein expression, including increased Hsp70 levels during CD95-mediated apoptosis. Here, we examined the mechanism ... -
A cell-based study exploring novel therapeutic approaches to target cell stress and cell death pathways in paediatric cancers
McCarthy, Nicole (NUI Galway, 2020-08-17)Paediatric cancer is the leading cause of death by disease in children. High mortality rates and long-term effects of conventional treatments suggest an urgent need for basic and translational research to allow treatment ... -
Cellular response to stress: role of autophagy and cell death in caspase-9 deficient cells
Pakos-Zebrucka, Karolina (2017-10-31)Chronic or unresolved stress can lead to cell death, and induction of apoptosis is crucial when the cellular adaptive mechanisms are not able to resolve persistent stress. Malfunction of the apoptotic process caused by ... -
Cellular responses to endoplasmic reticulum stress: Role of autophagy and cell death
Saveljeva, Svetlana (2014-12-03)This PhD thesis describes cellular responses to the induction of endoplasmic reticulum (ER) stress, focusing on the role of autophagy and cell death. Pro-survival role of unfolded protein response (UPR) is analysed by ... -
Decorated macrocycles via ring-closing double-reductive amination. Identification of an apoptosis inducer of leukemic cells that at least partially antagonizes a 5-HT2 receptor
Zhou, Jian; Reidy, Mairead; O'Reilly, Ciaran; Jarikote, Dilip V.; Negi, Arvind; Samali, Afshin; Szegezdi, Eva; Murphy, Paul V. (American Chemical Society, 2015-03-16)A build-couple-pair strategy, including double-reductive amination macrocyclization, has been used to generate decorated macrocycles (eannaphanes) with an embedded triazole and monosaccharide. Biological screening led to ... -
Decoy Receptors block tumour cell eradication by TRAIL - Molecular engineering of TRAIL to evade decoy receptors
O' Leary, Lynda (2012-06-29)Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a cytokine expressed by immune cells which selectively eradicates a wide range of cancer cells while leaving normal healthy cells unharmed. TRAIL binds ... -
Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under er stress conditions
Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu JM; Samali, Afshin (Informa UK Limited, 2014-11-02)Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and ... -
Deregulated expression of the hsp40 family members auxilin-1 and -2 is indicative of proteostasis imbalance and predicts patient outcome in ph+ leukemia
Vieri, Margherita; Geng, Huimin; Patterson, John B.; Panse, Jens; Wilop, Stefan; Samali, Afshin; Chevet, Eric; Masouleh, Behzad Kharabi (Springer Nature, 2015-12-01)Background: Proteostasis is defined by the orchestrated control of anabolic and catabolic protein pathways. Disruption of proteostasis results in cell stress and adaptation to proteostasis imbalance is mediated by adaptive ... -
Development of a novel companion diagnostic for IRE1α activity and its application to investigate the role of IRE1α in acute myeloid leukaemia cells
Creedican, Stuart (NUI Galway, 2020-08-28)The unfolded protein response (UPR) is an evolutionarily conserved mechanism activated in response to accumulation of unfolded protein (termed ER stress). Activation of the UPR is observed during many physiological processes ... -
Development of drugs targeting the human tRNA ligase RtcB in breast cancer
Nandy, Argha (NUI Galway, 2019-02-15)The RNA ligase RtcB has been shown to regulate RNA function by direct exon ligation of spliced XBP1 messenger RNA cleaved by the endoplasmic reticulum (ER) stress sensor IRE1α. Ligation by RtcB leads to the expression of ... -
Disruption of microRNA Biogenesis Confers Resistance to ER Stress-Induced Cell Death Upstream of the Mitochondrion
Samali, Afshin (2013)Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown ... -
Disruption of microrna biogenesis confers resistance to er stress-induced cell death upstream of the mitochondrion
Cawley, Karen; Logue, Susan E.; Gorman, Adrienne M.; Zeng, Qingping; Patterson, John; Gupta, Sanjeev; Samali, Afshin (Public Library of Science (PLoS), 2013-08-19)Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown ... -
Don't lose heart - therapeutic value of apoptosis prevention in the treatment of cardiovascular disease
Reeve, Janice L. V.; Duffy, Angela M.; O'Brien, Timothy; Samali, Afshin (Wiley-Blackwell, 2005-07-01)Cardiovascular disease is a leading cause of death worldwide. Loss of function or death of cardiomyocytes is a major contributing factor to these diseases. Cell death in conditions such as heart failure and myocardial ... -
Dr4-selective tumor necrosis factor-related apoptosis-inducing ligand (trail) variants obtained by structure-based design
Tur, Vicente; van der Sloot, Almer M.; Reis, Carlos R.; Szegezdi, Eva; Cool, Robbert H.; Samali, Afshin; Serrano, Luis; Quax, Wim J. (American Society for Biochemistry & Molecular Biology (ASBMB), 2008-05-12)Tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL) is a potential anticancer agent that selectively induces apoptosis in a variety of cancer cells by interacting with death receptors DR4 and DR5. TRAIL can ... -
Drugging the unfolded protein response in acute leukemias
Kharabi Masouleh, Behzad; Chevet, Eric; Panse, Jens; Jost, Edgar; O’Dwyer, Michael; Bruemmendorf, Tim H.; Samali, Afshin (Springer Nature, 2015-07-16)The unfolded protein response (UPR), an endoplasmic reticulum (ER) stress-induced signaling cascade, is mediated by three major stress sensors IRE-1 alpha, PERK, and ATF6 alpha. Studies described the UPR as a critical ... -
Dual ire1 rnase functions dictate glioblastoma development
Lhomond, Stéphanie; Avril, Tony; Dejeans, Nicolas; Voutetakis, Konstantinos; Doultsinos, Dimitrios; McMahon, Mari; Pineau, Raphaël; Obacz, Joanna; Papadodima, Olga; Jouan, Florence; Bourien, Heloise; Logotheti, Marianthi; Jégou, Gwénaële; Pallares‐Lupon, Néstor; Schmit, Kathleen; Le Reste, Pierre‐Jean; Etcheverry, Amandine; Mosser, Jean; Barroso, Kim; Vauléon, Elodie; Maurel, Marion; Samali, Afshin; Patterson, John B; Pluquet, Olivier; Hetz, Claudio; Quillien, Véronique; Chatziioannou, Aristotelis; Chevet, Eric (EMBO, 2018-01-08)Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor aggressiveness. Evidence suggests that the endoplasmic reticulum (ER), a major site for protein folding and quality control, plays a critical ... -
Endoplasmic reticulum stress induces ligand-independent TNFR1-mediated necroptosis in L929 cells
Samali, Afshin (2015)Endoplasmic reticulum (ER) stress-induced cellular dysfunction and death is associated with several human diseases. It has been widely reported that ER stress kills through activation of the intrinsic mitochondrial apoptotic ...