Dr Fiyaz Mohammed

Institute of Immunology and Immunotherapy
Lecturer in Biomedical Structural Biology

Contact details

Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
Robert Aitken Institute of Clinical Research
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Fiyaz is a Lecturer in Biomedical Structural Biology in the Institute of Immunology and Immunotherapy, University of Birmingham. His research focuses on investigating immune cell surface receptor/ligand interactions relevant to cancer using X-ray crystallography. He has published a number of peer reviewed research papers on clinically relevant immune receptor recognition events including those underpinning alloreactive T cell receptor/peptide-MHC recognition and T cell recognition of post-translationally modified peptides. His currently focussed on understanding the molecular and structural basis gamma delta T cell recognition.

Qualifications

  • Lecturer in Biomedical Structural Biology, 2012
  • PhD in X-ray Crystallography, 2001
  • BSc (Hons) in Biochemistry, 1996

Biography

Fiyaz obtained a BSc (Hons) in Biochemistry (1996) from the University of Wolverhampton. He gained extensive experience in protein X-ray crystallography methods whilst undertaking a PhD and subsequent postdoctoral studies in the groups of Professors Steve Wood and Jon Cooper at the University of Southampton. His research focused on determining the structure and catalytic mechanism of key enzymes linked to bipolar disorder, acute intermittent porphyria, degradation of xenobiotic compounds and the bacterial electron transport chain. In 2004 he came to the University of Birmingham to join the laboratory of Professor Benjamin Willcox as a research fellow studying the molecular and structural basis of clinically important immune receptor recognition events. In particular, he made significant contributions to those underpinning alloreactive TCR-pMHC recognition events and T cell recognition of post-translationally modified peptides. In 2012 he was appointed a Lecturer in Biomedical Structural Biology focused on investigating the immune cell surface receptor/ligand interactions relevant to cancer using X-ray Crystallography. His current focus is on understanding the molecular basis of gamma delta T cell recognition, an area that is of growing interest to industry. He is also exploring the structural and molecular basis of CD248 and CLEC14A function, two key family members that have roles in tumour angiogenesis and inflammation. Finally, Fiyaz has a growing interest in understanding the structure and function of desmosomal proteins which is important for understanding the biology of epithelial tissues and cardiac muscle in normal development and disease.

Teaching

Dr Mohammed currently leads the Cancer Immunology and Immunotherapy module as part of the MRes in Cancer Sciences course. He also contributes to the following programmes:

Postgraduate supervision

Dr Mohammed supervises PhD and MSc students.

If you are interested in studying with Dr Mohammed please contact him on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Dr Mohammed’ research focus is on investigating immune cell surface receptor/ligand interactions relevant to cancer using structural biology approaches such as X-ray crystallography. In particular, he has a long standing interest in the following key areas:

Gamma delta 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.

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.

Stem Cell Transplantation (SCT)

NKG2D is an activatory receptor that is expressed on a range of immune effector cells which engages stress induced ligands which include members of the ULBP family. Recent studies have highlighted that polymorphisms in the stress induced molecule, ULBP6, in patients with haematological malignancies play a critical role in determining the outcome of SCT. Dr Mohammed, in collaboration with Professors Paul Moss and Ben 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.

Tumour Angiogenesis

Dr Mohammed is interested in examining the structure, function and ligand identification of CLEC14A and CD248 (in collaboration with Professors Roy Bicknell and Chris Buckley), a group of receptors that are heavily implicated in tumour angiogenesis and progression. This is likely to facilitate design of small molecule drugs as novel anti-angiogenic therapeutics for cancer.

For further information visit: http://ciic.org.uk.

Other activities

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 sits on the University of Birmingham Protein Expression Facility Advisory Board.

Publications

SalimM*, KnowlesT*, BakerAT*, DaveyMS, JeevesM,  SridharP, WilkieJ, WillcoxCR, KadriH, Taher ET, Vantourout P, Hayday A,  MehellouY, Mohammed F*, Willcox BE*. BTN3A1 discriminates γδ T cell phosphoantigens from non-antigenic small molecules via a conformational sensor in its B30.2 domain. ACS Chem. Biol., 2017, 12 (10), pp 2631–2643 doi: 10.1021/acschembio.7b00694

Khan KA, Naylor AJ, Khan A, Noy PJ, Mambretti M, Athwal J, Korzystka A, Buckley CD, Willcox BE, Mohammed F and 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 Jul 3. doi: 10.1038/onc.2017.214

Mohammed F*, Stones DH*, Cobbold M, Zarling AL, Salim M, Barret-Wilt GA, Shabanowitz J, Hunt DF, Engelhard VH and Willcox-BE. The antigenic identity of human class I MHC phosphopeptides is critically dependent upon phosphorylation status. Oncotarget. 2017 Apr 8. doi: 10.18632/oncotarget.16952

Zuo-J*, Willcox-CR*, Mohammed-F*, Davey M, Hunter-S, Khan KA, Antoun A, Croudace J, Inman C, Parry H, Briggs D, Malladi R, Willcox BE and Moss PAH. A disease-associated ULBP6 polymorphism modulates NKG2D-mediated immunity by creating an ultra-stable NKG2D receptor/ligand interaction. Sci Signal. 2017 May 30;10(481). doi: 10.1126/scisignal.aai8904

Davey MS*, Willcox CR*, Joyce SP, Ladell K, Kasatskaya S, McLaren JE, Hunter SJ, Salim M, Mohammed F, Price DA, Chudakov DM and Willcox BE.  Clonal selection in the human Vδ2-negative γδ T cell repertoire suggests TCR-dependent ‘adaptive stress surveillance’. Nat Commun. 2017 Mar 1;8:14760. doi: 10.1038/ncomms14760

Willcox C, Mohammed F and Willcox B.E. Resolving the mystery of pyrophosphate antigen presentation. Nature Immunol 14, 886-887 (2013)

Simpson AA*, Mohammed F*, Salim M, Tranter A, Rickinson AB, Stauss HJ, Moss PAH, Steven NM and Willcox BE. Structural and energetic evidence for highly peptide-specific tumour antigen targeting via Allo-MHC restriction. Proc Natl Acad Sci  108(52), 21176-81 (2011)

Cheng H, Mohammed F, NamG, Chen Y, Qi J Garner LI, Allen RL, YanJ, Willcox BE and Gao GF. Crystal structure of Leukocyte Immunoglobulin-like Receptor LILRB4: a myeloid inhibitory receptor involved in immune tolerance. J. Biol. Chem 286 (20): 18013-18025 (2011)

Gill R, Kolstoe SE, Mohammed F, Al-Dbass A, Cooper JB, Wood SP, Shoolingin-Jordan P. The Structure of Human Porphobilinogen Deaminase at 2.8 Å: The molecular basis of acute intermittent porphyria. Biochem J 420(1), 17-25 (2009)

Mohammed F*, Cobbold M*, Zarling AL, Salim M, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Engelhard VE, Willcox BE. Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for presentation of transformed self. Nature Immunol 9, 1236-1243 (2008)

Salim M*, Knowles TJ*, Hart R*, Mohammed F, Woodward MJ, Willcox CR, Overduin M, Hayday AC and Willcox-BE (2016) Characterisation of a putative receptor binding surface on Skint1, a critical determinant of dendritic epidermal γδ T cell selection. J Biol Chem 291(17):9310-21 (2016)

Fogl C*, Mohammed F*, Al-Jassar C, Jeeves M, Knowles TJ, Rodriguez-Zamora P, White SA, Odintsova E, Overduin M and Chidgey M (2016) Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin. Nat Commun 7:10827

Willcox C, Mohammed F and Willcox BE (2013) Resolving the mystery of pyrophosphate antigen presentation. Nat Immunol 14(9):886-7 (2013)

Simpson AA*, Mohammed F*, Salim M, Tranter A, Rickinson AB, Stauss HJ, Moss PA, 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 U S A 108(52):21176-81 (2011)

Cheng H, Mohammed F, Nam G, Chen Y, Qi J, Garner LI, Allen RL, Yan J, Willcox BE and Gao GF (2011) Crystal structure of Leukocyte Ig-like Receptor LILRB4 (ILT3/LIR-5/CD85k): a myeloid inhibitory receptor involved in immune tolerance. J Biol Chem 286(20):18013-25 (2011)

Gill R, Kolstoe SE, Mohammed F, Al D-bass A, Mosely JE, Sarwar M, Cooper JB, Wood SP and Shoolingin-Jordan P (2009) Structure of human porphobilinogen deaminase at 2.8 Å: the molecular basis of acute intermittent porphyria. Biochem J 420(1):17-25 (2009)

Nicholls S*, Piper KP*, Mohammed F, Dafforn TR, Tenzer S, Salim M, Mohendra P, Craddock C, van Endert P, Schild H, Cobbold M, Engelhard VH, Moss PA 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 U S A 106(10):3889-94 (2009)

Mohammed F*, Cobbold M*, Zarling AL, Salim M, Barrett-Wilt GA, Shabanowitz J, Hunt DF, Engelhard VE and Willcox BE (2008) Phosphorylation-dependent interaction between antigenic peptides and MHC class I: a molecular basis for presentation of transformed self. Nat Immunol 9(11):1236-43 (2008)

*authors contributed equally to this study

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