Dr Peter Monk BSc PhD
Department of Infection and Immunity
The University of Sheffield
Beech Hill Road
Sheffield S10 2RX
I began my career in the Biochemistry Department in Sheffield in 1988 as a post-doctoral researcher, working for Professor Banks on chemoattractant signalling in monocytes, before working with Dr Birgit Helm on mast cell degranulation. In 1992, I became an independent researcher, funded by Arthritis Research UK to study the important pro-inflammatory mediator, complement fragment 5A (C5a).
In 1995, Arthritis Research UK awarded me a post-doctoral fellowship to establish my own laboratory, working on the interactions between C5a and its receptor. We were the first group to characterise the second C5a receptor, C5L2, now recognised to have important roles in inflammation and neurodegeneration. During this time, I also began work on the tetraspanin family of membrane proteins, identifying the hepatitis C virus E2 glycoprotein binding site on CD81.
I became a lecturer in the Department of Neurosciences in 2001 and was promoted to Senior Lecturer in 2007, before moving to the Department of Infection and Immunity in 2009. I became Reader in Immunology in 2013.
Complement fragment receptors
The complement cascade is a series of blood proteins forming a part of the immune system that responds to infection. Complement protein fragments (C4a, C3a) produced by activation of the cascade actually cause inflammation which is normally a good thing but, when excessively produced, they exacerbate inflammatory diseases and there are no drugs currently available to prevent this. We are investigating the molecular interactions that underlie complement fragment receptor (C5aR, C3aR, C5L2) functions with the aim of developing new drugs for anti-inflammatory therapy.
NMR structure of C5a.
This receptor activation domain is the turn-helix at base of the molecule
Tetraspanins have been implicated in many of the fundamental processes involved in the development and functioning of multicellular organisms, from sponges to man. These include cell fustion, migration, secretion, adhesion and signalling. Recently, several tetraspanins have been shown to have roles in microbial infections, including hepatitis C, HIV-1 and Chlamydia. Cell ingress and egress mechanisms involving tetraspanins are exploited by these intracellular pathogens. These mechanisms can be blocked by tetraspanin-specific reagents, suggesting that tetraspnins may be valuable drug targets. However, the molecular details of tetraspanin functions have yet to be fully elucidated. We are using mammalian and zebrafish models to further our understanding of this fascinating protein family.
Dimer of CD81 EC2 domains. This domain contains the HCV binding site
- MSc Molecular Medicine MED6006 (Allergy and Imunotherapy)
- Preclinical Medicine Laboratory-based SSC; student mentor
- BMS309 Neurobiological Basis of Brain Disease (the neuroimmunology of disease)
- MBB311 Molecular Immunology (innate immunity)
- MBB360 Third Year Undergraduate projects
- MBB460 Fourth Year Undergraduate Projects
- Member of British Society for Immunology; Biochemical Society, British Inflammation Research Association.
- INSERM scientific evaluation Infection and Immunity panel member
- Co-organiser for FASEB summer research conferences on tetraspanins
- Associate editor for BMC Immunology, Frontiers of Immunology
- Industry Consultancies
- Analysis of the C5a receptor ligand binding site
- Control of C5a function by the second C5a receptor, C5L2
- Development of C3a receptor antagonists
- The role of CD63 in secretory lysosomes
- Tetraspanin function in monocyte giant cell formation
- Tetraspanins and intracellular pathogens
- BBSRC DTG
For key publications see below. For a full list of publications click here.
- Unnewehr H, Rittirsch D, Flierl MA, Perl M, Denk S, Gebhard F, Huber-Lang M, Sarma JV, Zetoune F, Neff T, Ward PA, Weiss M, Schneider ME, Monk PN, Mihlan M & Barth H (2013) Changes and regulation of the c5a receptor on neutrophils during septic shock in humans. Journal of Immunology, 190(8), 4215-4225.
- Klos A, Wende E, Wareham KJ & Monk PN (2013) International Union of Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors.. Pharmacol Rev, 65(1), 500-543.
- Lewis A, Wan J, Baothman B, Monk PN, Suvarna SK & Peachell PT (2013) Heterogeneity in the responses of human lung mast cells to stem cell factor.. Clin Exp Allergy, 43(1), 50-59.
- Reis ES, Chen H, Ricklin D, Lambris JD, Sfyroera G, Monk PN & Köhl J (2012) C5a receptor-dependent cell activation by physiological concentrations of desarginated C5a: Insights from a novel label-free cellular assay. Journal of Immunology, 189(10), 4797-4805.
- Pavlovski D, Thundyil J, Taylor SM, Woodruff TM, Monk PN & Wetsel RA (2012) Generation of complement component C5a by ischemic neurons promotes neuronal apoptosis. FASEB Journal, 26(9), 3680-3690.
- Bellows-Peterson ML, Fung HK, Floudas CA, Kieslich CA, Zhang L, Morikis D, Wareham KJ, Monk PN, Hawksworth OA & Woodruff TM (2012) De novo peptide design with C3a receptor agonist and antagonist activities: Theoretical predictions and experimental validation. Journal of Medicinal Chemistry, 55(9), 4159-4168.
- Monk PN & Partridge LJ (2012) Tetraspanins - gateways for infection. Infectious Disorders - Drug Targets, 12(1), 4-17.
- Trikić MZ, Monk P, Roehl H & Partridge LJ (2011) Regulation of zebrafish hatching by tetraspanin cd63.. PLoS One, 6(5), e19683.
- Green LR, Monk PN, Partridge LJ, Morris P, Gorringe AR & Read RC (2011) Cooperative role for tetraspanins in adhesin-mediated attachment of bacterial species to human epithelial cells.. Infect Immun, 79(6), 2241-2249.
- Parthasarathy V, Martin F, Higginbottom A, Murray H, Moseley GW, Read RC, Mal G, Hulme R, Monk PN & Partridge LJ (2009) Distinct roles for tetraspanins CD9, CD63 and CD81 in the formation of multinucleated giant cells.. Immunology, 127(2), 237-248.
- Scola AM, Johswich KO, Morgan BP, Klos A & Monk PN (2009) The human complement fragment receptor, C5L2, is a recycling decoy receptor.. Mol Immunol, 46(6), 1149-1162.
- Barreiro O, Zamai M, Yanez-Mo M, Tejera E, Lopez-Romero P, Monk PN, Gratton E, Caiolfa VR & Sanchez-Madrid F (2008) Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms. J CELL BIOL, 183(3), 527-542.
- Monk PN, Scola AM, Madala P & Fairlie DP (2007) Function, structure and therapeutic potential of complement C5a receptors.. Br J Pharmacol, 152(4), 429-448.
- Wright AJ, Higginbottom A, Philippe D, Upadhyay A, Bagby S, Read RC, Monk PN & Partridge LJ (2007) Characterisation of receptor binding by the chemotaxis inhibitory protein of Staphylococcus aureus and the effects of the host immune response.. Mol Immunol, 44(10), 2507-2517.
- Cain SA & Monk PN (2002) The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74).. J Biol Chem, 277(9), 7165-7169.
- Monk PN, Pease JE & Barker MD (1994) C5a stimulus-secretion coupling in rat basophilic leukaemia (RBL-2H3) cells transfected with the human C5a receptor is mediated by pertussis and cholera toxin-sensitive G proteins.. Biochem Mol Biol Int, 32(1), 13-20.