The aim of my research is to understand the molecular mechanisms that govern how cells maintain the quality of proteins during cellular stress, towards developing novel strategies for therapeutic intervention in cancer and neurodegenerative diseases.
Of particular interest, we seek to gain structural and mechanistic insights into how the Unfolded Protein Response, a key cell signaling system that maintains protein homeostasis within the ER, is activated and how the signal is subsequently propagated.
We utilize a multidisciplinary approach that encompasses structural biology, biochemistry, and cellular techniques, to characterize proteins and complexes involved in ER stress pathways.
Lab webpage: http://www.imperial.ac.uk/ali-lab
et al., 2019, UPR proteins IRE1 and PERK switch BiP from chaperone to ER stress sensor, Nature Structural and Molecular Biology, Vol:26, ISSN:1545-9985, Pages:1053-1062
et al., 2019, Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1, Frontiers in Molecular Biosciences, Vol:6, ISSN:2296-889X
et al., 2018, In vitro FRET analysis of IRE1 and BiP association and dissociation upon endoplasmic reticulum stress., Elife, Vol:7
et al., 2015, Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling, EMBO Journal, Vol:34, ISSN:0261-4189, Pages:1589-1600
et al., 2015, Noncanonical binding of BiP ATPase domain to Ire1 and Perk is dissociated by unfolded protein C(H)1 to initiate ER stress signaling, Elife, Vol:4, ISSN:2050-084X
et al., 2014, Phosphoregulation of Ire1 RNase splicing activity., Nat Commun, Vol:5
Maruf MUATBELDPRNMCS-SAHCMMGRGJMWAICFEDALHP, 2011, Structure of the Ire1 autophosphorylation complex and implications for the unfolded protein response, Embo J, Vol:30, Pages:894-905
et al., 2006, Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex, Nature, Vol:440, ISSN:0028-0836, Pages:1013-1017