Browsing by Author "Szegezdi, Eva"
Now showing items 1-20 of 30
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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 ... -
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 ... -
Co-acting gene networks predict trail responsiveness of tumour cells with high accuracy
O’Reilly, Paul; Ortutay, Csaba; Gernon, Grainne; O’Connell, Enda; Seoighe, Cathal; Boyce, Susan; Serrano, Luis; Szegezdi, Eva (Springer Nature, 2014-01-01)Background: Identification of differentially expressed genes from transcriptomic studies is one of the most common mechanisms to identify tumor biomarkers. This approach however is not well suited to identify interaction ... -
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 ... -
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 ... -
Generation of natural killer cell-mimic nanoparticles to target tumour cells
Alizadeh Zeinabad, Hojjat (NUI Galway, 2022-05-30)Natural killer (NK) cells are effector immune cells in the innate immune system. It is increasingly recognised that NK cells play a crucial role eliminating emerging tumour cells. Some tumour cells however can escape and ... -
Guiding the killer and bringing in accomplices: bispecific antibody treatment for malignant melanoma
Szegezdi, Eva; Leverkus, Martin (Elsevier BV, 2016-02-01)Discovery of oncogene and immune checkpoint targeting has transformed melanoma therapy in the last 5 years. However, treatment of primary or secondary drug-resistant melanoma remains a challenge. Agents designed to activate ... -
Identification of decisive molecular interactions regulating resistance to apoptosis in tumour cells
O' Reilly, Paul (14-07-04)TRAIL is a member of the TNF family of cytokines which can selectively induce apoptosis in cancerous cells. For this reason recombinant TRAIL is being considered for the treatment of cancer. During their development cancer ... -
Identification of novel drug combinations for haematological malignancies
Reidy, Mairéad (2015-01-29)TNF-related apoptosis ligand (TRAIL) is a tumour selective cytokine with potential anti-cancer activity which is currently in clinical trials. Haematological malignancies along with several other cancers have showed varied ... -
Identifying novel drug therapies for acute myeloid leukaemia by targeting the interactions between leukaemia cells and bone marrow microenvironment
Dhami, Sukhraj Pal Singh (NUI Galway, 2019-10-25)Acute myeloid leukaemia (AML) is a malignancy caused by a block in differentiation in which aberrant leukemic stem cells drive the production of undifferentiated or partially differentiated leukemic blast cell clones. ... -
Identifying novel strategies to re-engage the apoptotic pathway for the treatment of cancer
Halpin-McCormick, Anna (2014-09-30)In chapter two we demonstrate that in non-transformed cells multiple signalling pathways control TRAIL resistance and they act in a redundant manner. This is contrary, however, to the resistance mechanisms found in tumour ... -
Kinetics in signal transduction pathways involving promiscuous oligomerizing receptors can be determined by receptor specificity: apoptosis induction by trail
Szegezdi, Eva; van der Sloot, Almer M.; Mahalingam, Devalingam; O'Leary, Lynda; Cool, Robbert H.; Muñoz, Inés G.; Montoya, Guillermo; Quax, Wim J.; de Jong, Steven; Samali, Afshin; Serrano, Luis (American Society for Biochemistry & Molecular Biology (ASBMB), 2012-01-02)Here we show by computer modeling that kinetics and outcome of signal transduction in case of hetero-oligomerizing receptors of a promiscuous ligand largely depend on the relative amounts of its receptors. Promiscuous ... -
Kinetics in signal transduction pathways involving promiscuous oligomerizing receptors can be determined by receptor specificity: Apoptosis induction by TRAIL
Szegezdi, Eva; Mahalingam, Devalingam (American Society for Biochemistry and Molecular Biology, 2012)Here we show by computer modeling that kinetics and outcome of signal transduction in case of hetero-oligomerizing receptors of a promiscuous ligand largely depend on the relative amounts of its receptors. Promiscuous ... -
Mechanisms of bone marrow-mediated drug resistance in acute myeloid leukaemia
O' Reilly, Eimear (NUI Galway, 2020-06-12)Acute myeloid leukaemia (AML) is a heterogenous clonal disorder characterised by the accumulation of immature, non-functional and highly proliferative blasts in the bone marrow and periphery. AML has a high relapse rate, ... -
Mechanisms of ER Stress-Mediated Mitochondrial Membrane Permeabilization
Gupta, Sanjeev; Cuffe, Lorraine; Szegezdi, Eva; Logue, Susan E.; Neary, Catherine; Healy, Sandra; Samali, Afshin (2010)During apoptosis, the process of mitochondrial outer membrane permeabilization (MOMP) represents a point-of-no-return as it commits the cell to death. Here we have assessed the role of caspases, Bcl-2 family members and ... -
Mediators of endoplasmic reticulum stress-induced apoptosis
Szegezdi, Eva; Logue, Susan E; Gorman, Adrienne M.; Samali, Afshin (Wiley-Blackwell, 2006-09-01)The efficient functioning of the endoplasmic reticulum ( ER) is essential for most cellular activities and survival. Conditions that interfere with ER function lead to the accumulation and aggregation of unfolded proteins. ... -
Metabolic flexibility permits mesenchymal stem cell survival in an ischemic environment
Mylotte, Louise A.; Duffy, Angela M.; Murphy, Mary; O'Brien, Timothy; Samali, Afshin; Barry, Frank; Szegezdi, Eva (Wiley-Blackwell, 2008-05-01)The application of mesenchyrnal stem cells (MSCs) for myocardial repair following ischemic injury is of strong interest, but current knowledge regarding the survival and retention of differentiation potency of stem cells ... -
N-glycosylation of mouse trail-r and human trail-r1 enhances trail-induced death
Dufour, Florent; Rattier, Thibault; Shirley, Sarah; Picarda, Gaelle; Constantinescu, Andrei Alexandru; Morlé, Aymeric; Zakaria, Al Batoul; Marcion, Guillaume; Causse, Sebastien; Szegezdi, Eva; Zajonc, Dirk Michael; Seigneuric, Renaud; Guichard, Gilles; Gharbi, Tijani; Picaud, Fabien; Herlem, Guillaume; Garrido, Carmen; Schneider, Pascal; Benedict, Chris Alan; Micheau, Olivier (Springer Nature, 2017-02-10)APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important ... -
Noxa contributes to the sensitivity of perk-deficient cells to er stress
Gupta, Sanjeev; Giricz, Zoltan; Natoni, Alessandro; Donnelly, Neysan; Deegan, Shane; Szegezdi, Eva; Samali, Afshin (Wiley-Blackwell, 2012-10-12)