Afshin Samali

Professor Afshin Samali

 

Career History

 

SFI Professor and Head of Biochemistry, NUIG, 2007

Ph.D. University College Cork (UCC), Ireland, 1993

B.Sc. National University of Ireland, Maynooth, Ireland, 1996

 


 

Research Interests


Cellular responses to endoplasmic reticulum-induced stress.


Mechanisms of apoptosis – in particular role of Bcl-2 family of proteins.


Cytokine engineering for cancer therapy.


Research Overview

 

The endoplasmic reticulum (ER) stress group studies the signalling pathways by which a cell responds to endoplasmic reticulum stress and how this molecular response influences cell fate. The ER is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the ER initiate a complex intracellular signal transduction pathway, known as the unfolded protein response (UPR). This response is an attempt to re-establish ER homeostasis but if the stress is too severe it can induce cell death. The switch from protection to destruction is thought to depend to a large extent on the nature and duration of the stress as well as the cell type. The importance of studies into the ER stress response is underscored by the involvement of this response in diseases such as cancer, myocardial infarction and neurodegenerative disorders such as Parkinson’s and Alzheimer’s.  
Our studies are currently focused in four main areas (1) Identification of molecules activated during the ER stress response and characterization of the signal transduction pathways involving these molecules; (2) Investigating the effects of Heat shock proteins (Hsps) on the ER stress response; (3) Studying the effect of Bcl-2 and its family members on ER stress responses and (4) Identification of novel targets for drug discovery efforts aimed at targeting the UPR.

 

Selection of key publications:


Healy SJ, Gorman AM, Mousavi-Shafaei P, Gupta S, Samali A (2009) Targeting the endoplasmic reticulum-stress response as an anticancer strategy. Eur J Pharmacol. 25;625(1-3):234-46


Szegezdi E, O’Reilly A, Davy Y, Vawda R, Taylor DL, Murphy M, Samali A, Mehmet H (2009) Stem cells are resistant to TRAIL receptor-mediated apoptosis. J Cell Mol. Med.( (In press )


Mahalingam D, Keane M, Pirianov G, Mehmet H, Samali A, Szegezdi E (2009). Differential activation of JNK1 isoforms by TRAIL receptors modulate apoptosis of colon cancer cell lines. Br J Cancer 100(9): 1415-24.


Duiker EW, de Vries EGE, Mahalingam M, Meersma GJ, Boersma-van Ek W, Hollema H, Lub-de Hooge MN, van Dam GM, Cool RH, Quax WJ, Samali A, van der Zee AGJ, de Jong S (2009) Enhanced anti-tumor efficacy of a DR5-specific TRAIL variant over rhTRAIL in a bioluminescent ovarian cancer xenograft model. Clin. Can. Res 15(6): 2048-57


Szegezdi E, Herbert KR, Kavanagh ET, Samali A, Gorman AM. (2008). Nerve growth factor blocks thapsigargin-induced apoptosis at the level of the mitochondrion via regulation of Bim. J Cell Mol Med. 12(6A): 2482-96


Tur V, van der Sloot AM, Reis CR, Szegezdi E, Cool RH, Samali A, Serrano L, Quax WJ. (2008). DR4-selective tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) variants obtained by structure-based design. J Biol Chem 283(29): 20560-8


Holohan C., Szegezdi E., Ritter T., O'Brien T., Samali A. (2008). Cytokine-induced beta-cell apoptosis is no-dependent, mitochondria-mediated and inhibited by BCL-X(L). J Cell Mol Med. 12: 591-606.


Reeve J.L., Szegezdi E., Logue S.E., Chonghaile T.N., O'Brien T., Ritter T., Samali A.  (2007). Distinct mechanisms of cardiomyocyte apoptosis induced by doxorubicin and hypoxia converge on mitochondria and are inhibited by Bcl-xL. J Cell Mol Med 11: 509-20.


Reeve J.L., Stenson-Cox C., O'Doherty A., Pörn-Ares I., Ares M., O'Brien T., Samali A. (2007). OxLDL-induced gene expression patterns in CASMC are mimicked in apoE-/- mice aortas. BiochemBiophys Res Commun 356: 681-6


Samali A., O'Mahoney M., Reeve J., Logue S., Szegezdi E., McMahon J., Fearnhead H.O.. (2007). Identification of an inhibitor of caspase activation from heart extracts; ATP blocks apoptosomeformation. Apoptosis 12: 465-74


 Patents:


Van der Sloot A.M., Tur V., Szegezdi E., Mullally M.M., Samali A., Serrano L., Quax W (2003) Improved cytokine design (UK0328261.3)


 Van der Sloot A.M., Tur V., Szegezdi E., Mullally M.M., Samali A., Serrano L., Quax W (2005) Improved cytokine design (WO200556596)


 O’Brien TBarry FLiew Yie Loong ASamali ADuffy A (2008) New pharmaceutical composition comprises activated endothelial progenitor cells (EPCs) or mesenchymal stem cell (MSCs) andosteopontin, useful for treating cardiovascular disease and diabetes associated vascular complications (WO2008107422-A1)


Tur V, van der Sloot AM, Reis CR, Szegezdi E, Cool RH, Samali A, Serrano L, Quax WJ. (2008). DR4-selective tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) variants obtained by structure-based design (UK0723059.2)


 Samali A., Szegezdi E., Mahalingham D., et al (2009) Trail variants for treating cancer (WO2009077857-A2)


 Rodrigues Dos Reis, C.R., Quax W.J., Samali A., Szegezdi E., Cool R.H., Van Der Sloot A.M.,  Serrano L., Tur V.,  (2009) Improved cytokine design (WO2009066174-A1)


 Gupta S, Samali A (2009) Protein Targets in Disease” 2009/0047

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