Research
I have worked in the field of complement research for the past twenty-five years. My expertise encompasses the role of complement in non-infectious pathologies, such as ischemia-reperfusion injury and traumatic brain injury, as well as infectious diseases, like bacterial pneumonia, Neisseria infection, and various parasitic diseases. For the past 15 years I have also been involved in projects aimed at the therapeutic inhibition of the lectin pathway of complement, thus benefiting patients suffering from atypical HUS or transplant-associated microangiopathies. My current research interests include:
- The role of complement activation in the pathogenesis of Covid-19
- Activation and regulation of the complement system
- Therapeutic inhibition of the complement system
- Complement evasion by pathogens
- The role of complement in the pathogenesis of ischemia and neurodegenerative disease
- Interaction between the complement and coagulation systems
Publications
Selected publications
Mercurio D, Oggioni M, Fumagalli S, Lynch NJ, Roscher S, Minuta D, Perego C, Ippati S, Wallis R, Schwaeble WJ, De Simoni MG. Targeted deletions of complement lectin pathway genes improve outcome in traumatic brain injury, with MASP-2 playing a major role. Acta Neuropathol Commun. 2020. 8:174.
Haleem KS, Ali YM, Yesilkaya H, Kohler T, Hammerschmidt S, Andrew PW, Schwaeble WJ, Lynch NJ. The Pneumococcal Surface Proteins PspA and PspC Sequester Host C4-Binding Protein To Inactivate Complement C4b on the Bacterial Surface. Infect Immun. 2019. 87: e00742-18.
Yaseen S, Demopulos G, Dudler T, Yabuki M, Wood CL, Cummings WJ, Tjoelker LW, Fujita T, Sacks S, Garred P, Andrew P, Sim RB, Lachmann PJ, Wallis R, Lynch N, Schwaeble WJ. Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2. FASEB J. 2017. 31:2210-2219.
Ribeiro CH, Lynch NJ, Stover CM, Ali YM, Valck C, Noya-Leal F, Schwaeble WJ, Ferreira A. Deficiency in mannose-binding lectin-associated serine protease-2 does not increase susceptibility to Trypanosoma cruzi infection. Am J Trop Med Hyg. 2015. 92:320-4.
Asgari E, Farrar CA, Lynch N, Ali YM, Roscher S, Stover C, Zhou W, Schwaeble WJ, Sacks SH. Mannan-binding lectin-associated serine protease 2 is critical for the development of renal ischemia reperfusion injury and mediates tissue injury in the absence of complement C4. FASEB J. 2014. 28:3996-4003.
Ali YM, Hayat A, Saeed BM, Haleem KS, Alshamrani S, Kenawy HI, Ferreira VP, Saggu G, Buchberger A, Lachmann PJ, Sim RB, Goundis D, Andrew PW, Lynch NJ, Schwaeble WJ. Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection. Proc Natl Acad Sci U S A. 2014. 111:5301-6.
Ali YM, Lynch NJ, Haleem KS, Fujita T, Endo Y, Hansen S, Holmskov U, Takahashi K, Stahl GL, Dudler T, Girija UV, Wallis R, Kadioglu A, Stover CM, Andrew PW, Schwaeble WJ. The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection. PLoS Pathog. 2012. 8:e1002793.
Schwaeble WJ, Lynch NJ, Clark JE, Marber M, Samani NJ, Ali YM, Dudler T, Parent B, Lhotta K, Wallis R, Farrar CA, Sacks S, Lee H, Zhang M, Iwaki D, Takahashi M, Fujita T, Tedford CE, Stover CM. Targeting of mannan-binding lectin-associated serine protease-2 confers protection from myocardial and gastrointestinal ischemia/reperfusion injury. Proc Natl Acad Sci U S A. 2011. 108:7523-8.
El Aswad BDW, Doenhoff MJ, El Hadidi AS, Schwaeble WJ, Lynch NJ. Use of recombinant calreticulin and cercarial transformation fluid (CTF) in the serodiagnosis of Schistosoma mansoni. Immunobiology. 2011. 216:379-85.
Schwaeble WJ, Ali YM, Lynch NJ, Wallis W. Complement in Infections. In: Immunology of Infectious Diseases. Kaufmann SHE, Rouse BT, and Sacks DL, eds. 2010. ASM Press, Washington DC.
Wallis R, Lynch NJ. Biochemistry and genetics of the collectins. In: Collagen-related lectins in innate immunity. Kilpatrick, D, ed. 2007. Research Signpost, Kerala, India.
Wallis R, Lynch NJ, Roscher S, Reid KB, Schwaeble WJ. Decoupling of carbohydrate binding and MASP-2 autoactivation in a variant MBL associated with immunodeficiency. J Immunol. 2005. 175:6846-51.
Lynch NJ, Khan S, Sandrini SM, Stover CM, Marston D, Presanis JS, Schwaeble WJ. Characterisation of the Lectin Pathway of Complement in Gallus gallus: Absence of MASP-1 in Birds. J Immunol. 2005. 174:4998-5006.
Lynch NJ, Roscher S, Hartung T, Morath S, Matsushita M, Maennel DN, Kuraya M, Fujita T, Schwaeble WJ. L-ficolin specifically binds to lipoteichoic acid, a cell wall constituent of Gram-positive bacteria, and activates the lectin pathway of complement. J Immunol. 2004. 172:1198-202.
Lynch NJ, Willis CL, Nolan CC, Roscher S, Fowler MJ, Weihe E, Ray DE, Schwaeble WJ. Microglial activation and increased synthesis of complement component C1q precedes blood-brain barrier dysfunction in rats. Mol Immunol. 2004. 40:709-16.
Wagner S, Lynch NJ, Walter W, Schwaeble WJ, Loos M. Differential expression of the murine mannose-binding lectins A and C in lymphoid and nonlymphoid organs and tissues. J Immunol. 2003. 170:1462-5.
Vinci G, Lynch NJ, Duponchel C, Lebastard TM, Milon G, Stover C, Schwaeble W, Tosi M. In vivo biosynthesis of endogenous and of human C1 inhibitor in transgenic mice: tissue distribution and colocalization of their expression. J Immunol. 2002. 169:5948-54.
Lynch NJ, Schneider H, Sim RB, Bickel U, Schwaeble WJ. In vivo pharmacokinetics of calreticulin S-domain, an inhibitor of the classical complement pathway. Int Immunopharmacol. 2002. 2:415-22.
Hampe J, Lynch NJ, Daniels S, Bridger S, Macpherson AJ, Stokkers P, Forbes A, Lennard-Jones JE, Mathew CG, Curran ME, Schreiber S. Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease. Gut. 2001. 48:191-7.
Hampe J, Shaw SH, Saiz R, Leysens N, Lantermann A, Mascheretti S, Lynch NJ, MacPherson AJ, Bridger S, van Deventer S, Stokkers P, Morin P, Mirza MM, Forbes A, Lennard-Jones JE, Mathew CG, Curran ME, Schreiber S. Linkage of inflammatory bowel disease to human chromosome 6p. Am J Hum Genet. 1999. 65:1647-55.
Lausen M, Lynch N, Schlosser A, Tornoe I, Saekmose SG, Teisner B, Willis AC, Crouch E, Schwaeble W, Holmskov U. Microfibril-associated protein 4 is present in lung washings and binds to the collagen region of lung surfactant protein D. J Biol Chem. 1999. 274:32234-40.
Stuart GR, Lynch NJ, Day AJ, Schwaeble WJ, Sim RB. The C1q and collectin binding site within C1q receptor (cell surface calreticulin). Immunopharmacology. 1997. 38:73-80.
Lynch NJ, Reid KB, van den Berg RH, Daha MR, Leigh LA, Ghebrehiwet B, Lim WB, Schwaeble WJ. Characterisation of the rat and mouse homologues of gC1qBP, a 33 kDa glycoprotein that binds to the globular 'heads' of C1q. FEBS Lett. 1997. 418:111-4.
