Professor Paul Crocker FRSE
Our research is aimed at understanding how immune cells utilise host glycans to regulate immune and inflammatory respones and translating this to human disease. All cells of the body are covered in a dense coating of glycans attached to proteins and lipids, some of which can act as ligands for lectin-like receptors expressed by cells of the innate and adaptive immune systems. We focus on the siglec family of sialic acid binding Ig-like lectins, many of which were discovered in my laboratory .
There are 15 siglecs in humans and 9 in mice, most of which are expressed in the immune system where they are thought to interact with host glycans to modulate immune and inflammatory responses. Our recent work has dissected in vivo functions of sialoadhesin (siglec-1/CD169) in (a) regulating autoimmune disease via interactions with activation-induced ligands on different T cell subsets and (b) promoting phagocytosis of the sialylated pathogen Campylobacter jejuni and triggering of MyD88-dependent cytokine and type I IFN responses . We have also recently discovered that murine siglec-E is an important negative regulator of beta2 integrin-dependent neutrophil inflammation in the lung.
Our current work is aimed at molecular dissection of the signalling pathways and identification of cis- and trans binding partners for siglecs involved in these biological functions.
Level 3 and Level 4 undergraduate lectures in Immunology.
4D01-Molecular Biology of Infection & Immunity
McMillan, S.J., Sharma, R.S., McKenzie, E.J., Richards, H.E., Zhang, J., Prescott, A., and Crocker, P.R. (2013). Siglec-E is a negative regulator of acute pulmonary neutrophil inflammation and suppresses CD11b beta2-integrin-dependent signaling. Blood 121, 2084-2094.
Kidder, D., Richards, H.E., Ziltener, H.J., Garden, O.A., and Crocker, P.R. (2013). Sialoadhesin ligand expression identifies a subset of CD4+Foxp3- T cells with a distinct activation and glycosylation profile. J Immunol 190, 2593-2602.
Klaas, M., Oetke, C., Lewis, L.E., Erwig, L.P., Heikema, A.P., Easton, A., Willison, H.J., and Crocker, P.R. (2012). Sialoadhesin promotes rapid proinflammatory and type I IFN responses to a sialylated pathogen, Campylobacter jejuni. J Immunol 189, 2414-2422.
Klaas M, Crocker PR. (2012) Sialoadhesin in recognition of self and non-self. Semin Immunopathol. 34:353-64.
Crocker PR, McMillan SJ, Richards HE. (2012) CD33-related siglecs as potential modulators of inflammatory responses.
Ann N Y Acad Sci. 1253:102-11.
Redelinghuys, P., Antonopoulos, A., Liu, Y., Campanero-Rhodes, M. A., McKenzie, E.,Haslam, S. M., Dell, A., Feizi, T. and Crocker, P. R. (2011) Early Murine T-lymphocyte Activation Is Accompanied by a Switch from N-Glycolyl- to N-Acetyl-neuraminic Acid and Generation of Ligands for Siglec-E. J Biol Chem. 286, 34522-34532.
Our research is expected to have impact on human immune and inflammatory diseases in terms of our basic understanding of the underlying pathologies. In the long-term, this may lead to improved therapies.