Christoph Licht

Director, Dialysis and Apheresis Program

Senior Scientist, Cell Biology Program

Dr. Christoph Licht is an international expert for complement-mediated kidney diseases. His work has advanced the understanding of the pathogenesis and management of aHUS and C3G. His lab has made major contributions to the understanding of the consequences of complement activation on platelets, neutrophils and endothelial cells, and has established a series of functional assays allowing for the testing of complement activation in patients with (suspected) complement-mediated diseases.

Dr. Licht also has a long-standing interest in chronic proteinuric kidney disease (such as in Alport Syndrome). He established one of the first registries of children with Alport Syndrome and demonstrated the treatment benefit of RAAS blockade in this cohort. He published international treatment guidelines for children with Alport Syndrome. He also demonstrated a central role for ET-1/ETBR as well as complement in the progression of chronic proteinuric kidney disease.

Research

Dr. Licht’s research has translational character and is focused on complement-mediated renal diseases, i.e. atypical haemolytic-uremic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN)/C3 Glomerulopathy (C3G). Besides exploring new complement-targeting treatments, his team investigates the cellular and molecular consequences of complement activation on endothelial and epithelial cells and their interactions with platelets and neutrophils.

They recently became interested in the presence and function of intracellular complement, in particular in skeletal muscle. The team investigates the role of complement in the pathogenesis of an expanding spectrum of complement-mediated diseases, including sickle cell disease, acute/chronic injury of neuronal tissue, and chronic proteinuric kidney disease. Most recently, they began investigating the role of complement in COVID-19 pathology, in particular the related injury of the vascular endothelium. 

Education

• 2011–2012: Certificate, Academic Certification in Paediatrics and Paediatric Nephrology, FRCP(C), Royal College of Physicians and Surgeons of Canada 
• 2008–2009: Certificate, Inaugural Certificate Program in Translational Medicine, Eureka Institute for Translational Medicine 
• 2006–2006: Certificate, Board Certification in Paediatric Nephrology, Düsseldorf, Germany 
• 2006–2006: Certificate, License in Paediatric and Paediatric Nephrology, College of Physicians and Surgeons of Ontario 
• 2005–2005: Post-doctorate, Habilitation, University of Cologne 
• 2002–2005: Post-doctorate, Clinical Fellowship - Fellow, Children's Hospital of the University of Cologne, Germany 
• 1999–2002: Post-doctorate, Post-doctoral Research Fellowship, University of Texas, Southwestern Medical Center at Dallas, Texas 
• 1998–1999: Post-doctorate, Clinical Fellowship - Fellow, Children's Hospital of the University of Cologne, Cologne, Germany 
• 1998–1998: Certificate, Board Certification in Paediatrics, Düsseldorf, Germany 
• 1992–1998: Post-doctorate, Postgraduate Training, Children's Hospital of the University of Cologne 
• 1992–1995: Certificate, Doctorate in Medicine (MD), Ruprecht Karls Universitat, Heidelberg 
• 1993–1993: Certificate, Certificate, Approbation as Physician, Stuttgart, Germany 
• 1983–1992: Certificate, Doctorate in Medicine (MD), Albert-Ludwigs Universität Freiburg

Employment

• 2018: Senior Scientist, Cell Biology Program, SickKids Research Institute
• 2017: Full Professor of Paediatrics, University of Toronto, Faculty of Medicine 
• 2011: Associate Professor Department of Paediatrics, Faculty of Medicine, University of Toronto 
• 2010: Associate Member Department of Laboratory Medicine & Pathobiology, School of Graduate Studies, Faculty of Medicine, University of Toronto 
• 2010: Director, Program for Dialysis and Apheresis Nephrology - Dialysis, The Hospital for Sick Children
• 2010: Director, Program for Dialysis & Apheresis, The Hospital for Sick Children 
• 2009: Associate Member Institute of Medical Science, School of Graduate Studies, Faculty of Medicine, University of Toronto 
• 2009: Associate Staff Physician, Division of Nephrology, University Health Network 
• 2007: Associate Staff Physician, Division of Emergency Medicine, The Hospital for Sick Children 
• 2006: Staff Physician, Division of Nephrology, The Hospital for Sick Children 
• 2014–2018: Senior Associate Scientist Program in Cell Biology, Research Institute, The Hospital for Sick Children 
• 2005–2017: Privatdozent (Lecturer) Department of Pediatrics, Faculty of Medicine, University of Cologne 
• 2006–2014: Associate Scientist Program in Cell Biology, Research Institute, The Hospital for Sick Children 
• 2006–2011: Assistant Professor Department of Paediatrics, Faculty of Medicine, University of Toronto 
• 2005–2006: Staff Physician, Division of Nephrology, Children's Hospital of the University of Cologne 

Recognitions

• 2014: CORD (Canadian Organization for Rare Disorders) Rarity Scientific Award (Nominated) Canadian Organization for Rare Disorders 
• 2012: Appointed Chair HUS International (previously European Pediatric Research Group for HUS) 
• 2012: Appointed Member Safety Board of the European Treatment Trial for Alport Syndrome 
• 2012: Appointed Member The Canadian Kidney Knowledge Translation and Generation Network (CANN-NET) 
• 2009: Appointed Member European DEAP-HUS Study Group 

Achievements

Served as international examiner for PhD defenses:

• 2019: University of Nijmegen, The Netherlands (Dr. Kioa L. Wijnsma) 
• 2019: University of Ghent, Belgium (Dr. Evelien Snauwaert) 
• 2020: University of Bristol, UK (Dr. Emily Bowen) 

Served as international reviewer for academic promotions: 

• University of Jordan – Promotion to full professor (Dr. Jumana Hanna Albaramki)
  

Served as invited reviewer for national and international grant agencies including: 

• CIHR project grants – regular CIA panel member (Canada) 
• Kidney Research UK (UK) 
• Medical Research Council - National Institute for Health Research (UK) 
• Rosetrees Trust (UK) 
• ERC-2020-COG (EU)
  

Served as reviewer for numerous top scientific journals: 

• Regular invitations 
• Journals including N Engl J Med: Blood; Kidney Int; J Am Soc Nephrol; Clin J Am Soc Nephrol; J Thromb Haemost
  

Served on scientific program committees for international conferences: 

• ASN 2014 
• IPNA 2019 
• ESPN 2020 
• ESPN 2021 (invited) 
• PAS/ASPN 2021 (invited)
  

Development of international clinical practice guidelines: 

• KDIGO – aHUS and C3G Goodship et al, Kidney Int 2017 
• IPNA / ESPN / HUSi – aHUS
  

Development of international guidelines for clinical trials in C3G: 

• NKF
  

Served as invited scientific expert on panels: 

• NKF – C3G Expert Opinion (online) 
• Global aHUS registry – aHUS and COVID-19 (webinar)
  

Invited guest professorship: 

• University of Ghent, Ghent, Belgium 

1. Riedl M, Schlam D, Noone D, Bruno V, Ortiz Sandoval, CG, Pluthero F, Kahr W, Bowman M, James P, Grinstein S, Licht C. Vascular endothelial cells evade complement-mediated membrane injury via Weibel-Palade body mobilization. J Thromb Haemost. 2020 (in print). Complement activation results in pore (MAC; C5b-9) formation on endothelial cells with subsequent immediate and massive Ca2+ influx. We demonstrate that endothelial cells are able to survive a complement attack via the secretion of von Willebrand factor: endothelial cells mobilize and fuse Weibel-Palade bodies to the cell membrane, thus patching the complement-mediated membrane defects.
   
2. Riedl M, Noone DG, Khan MA, Pluthero FG, Kahr WHA, Palaniyar N, Licht C. Complement activation induces neutrophil adhesion and neutrophil-platelet aggregate formation on vascular endothelial cells. Kidney Int Rep. 2016 Aug 31; 2(1):66-75. Manifestation of aHUS at disease onset or during flare ups most often follows an inflammatory / infectious insult. In an in vitro / ex vivo setting we for the first time demonstrate that PMNs adhere to endothelial cells in context of complement activation and provide a nidus for platelet aggregation – thus unraveling the mechanism of infection triggered aHUS manifestation. 
3. Noone D, Riedl M, Pluthero FG, Bowman M, Liszewski K, Lu L, Quan Y, Balgobin S, Schneppenheim RS, Ulrich B, James P, Atkinson P, Palaniyar N, Kahr W, Licht C. Von Willebrand Factor regulates complement on endothelial cells. Kidney Int. 2016 Jul; 90(1):123-134. Until recently TTP and aHUS were considered distinct entities with different pathomechanisms – ADAMTS13 defects in TTP, complement over activation in aHUS. We demonstrate for the first time a pathomechanistic link between TTP and aHUS: various complement proteins (including C3, C5 and C5b-9) can bind to vWF, and vWF acts as (negative) complement regulators.
   
4. Legendre C*, Licht C*, Muus P*, Greenbaum L, Babu S, Bedrosian C, Bingham C, Cohen D, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman R, Gaber A, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nurnberger J, Ogawa M, Remuzzi G, Ospedaliera OR, Richard T, Sberro-Soussan R, Severino B, Sheerin N, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab for the treatment of atypical hemolytic-uremic syndrome. N. Engl. J. Med. 2013 Jun 6; 368(23):2169-2181. (PA) *Equally contributing principal authors. We co-lead an international, multicentric trial demonstrating safety and efficacy of the complement (C5) blocker eculizumab in children with both acute and chronic aHUS.
   
5. Licht C, Pluthero FG, Li L, Christensen H, Habbig S, Hoppe B, Geary DF, Zipfel PF, Kahr WHA. Platelet-associated complement Factor H in normal individuals and patients with atypical HUS. Blood. 2009 Nov 12; 114(20):4538-4545. We demonstrate the presence and functional relevance of CFH in platelets: (i) platelets carry CFH; (ii) platelet CFH is not stored in one of the known platelet granules; (iii) platelets can uptake CFH, but platelet precursor megacaryocytes also produce CFH; (iv) CFH can be released from platelets; (v) platelets exposed to an inhibiting CFH autoantibody, become activated, a phenomenon, which can be prevented via supra-physiological doses of CFH.