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Cambridge Infectious Diseases

An Interdisciplinary Research Centre at the University of Cambridge

Studying at Cambridge

 

Professor Paul Lehner

Departments and Institutes

Medicine:

Research Interests

We study MHC I molecules and other critical receptors of the immune system, and their modulation by viruses. We found that herpesviruses pirated ubiquitin E3 ligases from their vertebrate hosts. These viral E3 ligases ubiquitinate and downregulate critical receptors of the immune system. Ubiquitin E3 ligases and receptor ubiquitination have emerged as a critical means of regulating receptor cell surface expression.

 

Our laboratory studies:

 

(i) mechanisms used by viruses to evade immune recognition, particularly the MHC class I antigen presentation pathway

(ii) the role of ubiquitin in the regulation of cell surface receptors, including the use of siRNA screens to identify the key enzymes of the ubiquitination pathway regulating these receptors.

(iii) the use of quantitative proteomics (SILAC) to identify cell surface receptors downregulated by intracellular pathogens.

(iv) components of the endosomal sorting machinery used by internalised, ubiquitinated cell surface receptors.

 

Key Publications

Thomas, M, Boname, JM, Field, S, Nejentsev, S, Salio, M, Cerundolo, V, Wills M, Lehner PJ. (2008). Downregulation of NKG2D and NKp80 ligands by Kaposi’s sarcoma-associated herpesvirus K5 protects against NK cell cytotoxicity Proc Natl Acad Sci 105:1656–61

Floto, RA, MacAry, PA, Boname, JM, Mien, TS, Kampmann, B, Hair, JR, Huey, OS, Houben, EN, Pieters, J, Day, C, Oehlmann, W, Singh, Smith, KGC and Lehner, PJ (2006), “Dendritic Cell Stimulation by Mycobacterial HSP70 is Mediated Through CCR5”, Science 314:454–8

Duncan, LM, Piper, S, Dodd, RB, Saville, MK, Sanderson, CM, Luzio JP and Lehner PJ (2006) Lysine-63 Linked Ubiquitination Is Required For Endolysosomal Degradation of Class I Molecules EMBO Journal 25:1635–1645