Dr Fiyaz Mohammed is a protein crystallographer with a long standing interest in immune receptor structure and function.
Lecturer in Biomedical Structural Biology, Institute of Immunology and Immunotherapy, College of Medical Sciences and Dentistry, University of Birmingham
Background and Research focus
Dr Mohammed is a Lecturer in Biomedical Structural Biology who is focussed on investigating immune cell surface receptor/ligand interactions relevant to cancer using X-ray crystallography. In particular, he has a long standing interest in post translational immunology. Phosphopeptide antigens are emerging as a novel class of tumour-associated antigen presented by MHC molecules and recognised by T cells. Since disregulated phosphorylation is a hallmark of malignant transformation, presentation of an altered repertoire of phosphopeptide antigens on cancer cells may represent a distinct and therapeutically targetable immunological signature of “transformed self”. Fiyaz is investigating the molecular basis of phosphopeptide presentation by MHC molecules and recognition by T-cells. These studies should establish the mode of presentation for a key subset of MHC-restricted tumour associated phosphopeptides and facilitate attempts to target them therapeutically. Latterly, Dr Mohammed has developed an interest in gamma delta (γδ) T cell recognition. γδ T cells are poorly understood class of lymphocyte strongly implicated in surveillance of cellular stress recognizing target cells that are infected or transformed. In collaboration with Professor Ben Willcox, Dr Mohammed is focused on understanding how γδ T cell ligands are recognized at a molecular level.
X-ray crystallography; tumour immunology; post-translational immunology; receptor/ligand interactions; protein expression and purification.
Fiyaz has developed an interest in defining the role of NKG2D ligands in lymphoid stress recognition in cancer. NKG2D is an activatory receptor that is expressed on a range of immune cells which engages stress induced ligands. Recent studies have shown that polymorphisms in ULBP6, a stress induced ligand, in patients with haematological malignancies play a critical role in determining Stem Cell Transplantation (SCT) outcome. Dr Mohammed, in collaboration with Professors Moss and Willcox, is examining the molecular properties of the NKG2D/ULBP6 complex interaction with the aim of defining the mechanisms underlying curative anti-tumour responses following SCT. In collaboration with Professor Roy Bicknell, Fiyaz is interested examining the structure, function and ligand identification of CLEC14A, a receptor that is heavily implicated in tumour angiogenesis. This study is likely to facilitate design of small molecule drugs as novel anti-angiogenic therapeutics for cancer. Fiyaz also makes substantial contributions to teaching at many levels. He is currently the module lead in Cancer Immunology and Immunotherapy as part of the MRes Cancer Sciences Programme. Moreover, he lectures on structural biology techniques and tumour immunology to undergraduates and postgraduates reading Immunology, Biology and Pharmacogenomics. He is also closely affiliated with the Cancer Immunology and Immunotherapy Centre (CIIC) with a major role in developing and maintaining the CIIC website. Finally, he is the Institute Lead for Equality and Diversity and also sits on the University of Birmingham Protein Expression Facility Advisory Board.
Davey MS*, Willcox CR*, Hunter S*, Kasatskaya SA, Remmerswaal EBM, Salim M, Mohammed F, Bemelman FJ, Chudakov DM, Oo YH, Willcox BE. The human Vδ2(+) T-cell compartment comprises distinct innate-like Vγ9(+) and adaptive Vγ9(-) subsets. Nat Commun. 2018 May 2;9(1):1760. doi: 10.1038/s41467-018-04076-0.
Mohammed F*, Stones DH*, Zarling AL, Willcox CR, Shabanowitz J, Cummings KL, Hunt DF, Cobbold M, Engelhard VH, Willcox BE. The antigenic identity of human class I MHC phosphopeptides is critically dependent upon phosphorylation status. Oncotarget. 2017 Apr 8;8(33):54160-54172. doi: 10.18632/oncotarget.16952.
Salim M*, Knowles TJ*, Baker AT*, Davey MS, Jeeves M, Sridhar P, Wilkie J, Willcox CR, Kadri H, Taher TE, Vantourout P, Hayday A, Mehellou Y, Mohammed F*, Willcox BE*. BTN3A1 Discriminates γδ T Cell Phosphoantigens from Nonantigenic Small Molecules via a Conformational Sensor in Its B30.2 Domain. ACS Chem Biol. 2017 Oct 20;12(10):2631-2643. doi: 10.1021/acschembio.7b00694.
Khan KA, Naylor AJ, Khan A, Noy PJ, Mambretti M, Lodhia P, Athwal J, Korzystka A, Buckley CD, Willcox BE, Mohammed F, Bicknell R. Multimerin-2 is a ligand for group 14 family C-type lectins CLEC14A, CD93 and CD248 spanning the endothelial pericyte interface. Oncogene. 2017 Nov 2;36(44):6097-6108. doi: 10.1038/onc.2017.214. Epub 2017 Jul 3.
Zuo J*, Willcox CR*, Mohammed F*, Davey M, Hunter S, Khan K, Antoun A, Katakia P, Croudace J, Inman C, Parry H, Briggs D, Malladi R, Willcox BE, Moss P. A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D ligand binding. Sci Signal. 2017 May 30;10(481). pii: eaai8904. doi: 10.1126/scisignal.aai8904
Davey MS*, Willcox CR*, Joyce SP, Ladell K, Kasatskaya SA, McLaren JE, Hunter S, Salim M, Mohammed F, Price DA, Chudakov DM, Willcox BE. Clonal selection in the human Vδ1 T cell repertoire indicates γδ TCR-dependent adaptive immune surveillance. Nat Commun. 2017 Mar 1;8:14760. doi: 10.1038/ncomms14760.
Fogl C*, Mohammed F*, Al-Jassar C*, Jeeves M, Knowles TJ, Rodriguez-Zamora P, White SA, Odintsova E, Overduin M, Chidgey M. Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin. Nat Commun. 2016 Mar 3;7:10827. doi: 10.1038/ncomms10827.
Mohammed-F*, Simpson AA*, Salim M, Tranter A, Rickinson AB, Stauss-HJ, Moss PAH, Steven NM and Willcox BE. (2011). Structural and energetic evidence for highly peptide-specific tumor antigen targeting via Allo-MHC-restriction. Proc Natl Acad Sci 108(52):21176-81
Nicholls S*, Piper KP*, Mohammed F, Dafforn TR, Salim M, Tenzer S, van Endert P, Schild H, Cobbold M, Engelhard VH, Moss PAH and Willcox BE. (2009). Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition. Proc Natl Acad Sci 106(10):3889-94.
Mohammed F*, Cobbold M*, Zarling AL, Salim M, Barret-Wilt GA, Shabanowitz J, Hunt DF, Engelhard VH and Willcox BE. (2008). Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for the presentation of transformed self. Nat Immunol 9(11): 1236-43
*These authors contributed equally