About Sickkids
About SickKids

Christoph Licht, MD

The Hospital for Sick Children
Staff Physician
Nephrology

Research Institute
Senior Associate Scientist
Cell Biology

University of Toronto
Associate Professor
Department of Paediatrics

Associate Member
Institute of Medical Sciences (cross appointed)

Associate Member
Laboratory Medicine and Pathobiology (cross appointed)


Phone: 416-813-7654 ext. 202058
Fax: 416-813-6271
e-mail: christoph.licht@sickkids.ca

Brief Biography

Dr. Christoph Licht accepted a position as Assistant Professor at the University of Toronto in 2006 and joined the Division of Nephrology at The Hospital for Sick Children as a staff physician and the SickKids Research Institute as an Associate Scientist. In addition, he was appointed Associate Member of the Institute of Medical Science Graduate Faculty at the University of Toronto.

Dr Licht’s research focuses on complement-mediated renal diseases such as atypical haemolytic-uremic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN). The nature of his research is translational and includes clinical and basic research. He established an international registry as well as clinical tests allowing for a comprehensive genetic and biochemical work-up of patients with complement-mediated renal diseases. In addition, Dr Licht established a research program focusing on the interface of complement and coagulation in platelets in HUS.

In collaboration with Dr. Walter Kahr, a SickKids haematologist, he works on the morphological and functional characterization of the components of the complement system, especially complement Factor H (CFH), in platelets. These results may ultimately change our understanding of the pathophysiology of aHUS and may allow for the development of new treatment strategies not only for aHUS but also other, clot related diseases.

Dr. Licht is member of the “European Pediatric Research Group for HUS” and associate member of the “European Working Party for the Genetics of Complement-Mediated Diseases”.

Clinical Care Activities

  • Staff physician in the Division of Nephrology (The Hospital for Sick Children)
  • Associate staff physician in the Division of Nephrology (University Health Network, Toronto General Hospital)
  • Registry for complement-mediated renal diseases in children
  • PI Canada for Alexion sponsored aHUS treatment trial with Eculizumab

Research Interests

My research has translational character and is mainly focused on complement-mediated renal diseases, i.e. atypical haemolytic-uremic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN).

  • We identified a novel mutation in the regulatory domain of complement Factor H (CFH) resulting in the loss of CFH co-factor activity causes MPGN type II (dense deposit disease, DDD) [Licht al, Kidney Int 2006].
  • We demonstrated that a defect in CFH related proteins 1 and 3 (CFHR1/3) results in aHUS [Zipfel et al, PLoS Genetics 2007].
  • We defined a new aHUS sub-group termed DEAP HUS (deficiency of CFHR proteins and CFH autoantibody positive), which is characterized by the presence of CFH autoantibodies in patients with CFHR1/3 deficiency [Jozsi and Licht et al, Blood 2008].

Furthermore, I am interested in chronic proteinuric kidney diseases (e.g. Alport syndrome).

Research Activities

My current research focuses on the interface of the coagulation and complement system. In particular, I am interested in the role of CFH in the regulation of platelet function in aHUS. We hypothesize a novel scenario for the progression of aHUS in children, in which a breakdown in CFH-mediated inhibition of the alternative complement pathway on the surface of platelets directly triggers their activation. We will examine this hypothesis via experiments involving material from normal donors and children with aHUS to:

  1. determine platelet uptake, release and cellular localization of CFH and map its interactions with other platelet proteins
  2. determine the role of CFH in complement-mediated platelet activation
  3. establish the relevance of platelet-CFH interactions to the pathophysiology of aHUS in children.

Our results will contribute to a better understanding of aHUS, establishing the basis for the development of improved methods for monitoring disease progression, assessing the efficacy of existing treatments and evaluating new, less risky and more effective treatments.

Our group has extensive experience both in the treatment of children with aHUS, and in basic research concerning the complement system, blood coagulation, and platelets. Techniques currently used in my laboratory include platelet preparation, coagulation assays, immunofluorescence staining and imaging by spinning disk confocal laser microscopy, and protein analysis using immunoblotting. In addition, access to numerous state of the art core facilities includes DNA sequencing, mass-spectrometry, and flow cytometry.

Future Research Interests

  • Pathogenesis and treatment of complement-mediated renal diseases
  • Role of complement in chronic proteinuric kidney diseases (e.g. Alport syndrome)

External Funding

Heart and Stroke Foundation of Ontario (HSFO)
Funding Period: July 1, 2009 – June 30, 2012 (3 years)
Co-Investigator: Dr. Walter H. A. Kahr
Title: Atypical Hemolytic Uremic Syndrome: A New Pathological Role for Complement and Coagulation Control in Platelets.

Publications

(PA) Principal Author; (SRI) Senior Responsible Investigator; (CPA) Co-Principal Author; (C) Collaborator

 El-Hout Y, Licht C, Pippi Salle JL, Ngan BY, Bagli DJ, Lorenzo AJ, Farhat WA:  Hypertension in children with poorly functioning unilateral kidneys: predictors of resolution after nephrectomy.  BJU Int., 2010: 106: 9: 1376-80.  C

Wine E, Shen-Tu G, Gareau MG, Goldberg HA, Licht C, Ngan BY, Sorensen ES, Greenaway J, Sodek J, Zohar R, Sherman PM: Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.  Am. J. Pathol., 2010: 177: 3: 1320-32.  C

Zipfel PF, Mache C, Müller D, Licht C, Wigger M, Skerka C; for the European DEAP-HUS Study Group: DEAP-HUS: Deficiency of CFHR plasma proteins and autoantibody-positive form of hemolytic uremic syndrome.  Pediatr. Nephrol., 2010: 25: 10: 2009-19.  C

Chaturvedi S, Licht C, Langlois V:  Hemolytic uremic syndrome caused by Bordetella pertussis infection.  Pediatr. Nephrol., 2010: 25: 1361-4.  C

De S, Waters AM, Segal AO, Trautmann A, Harvey EA, Licht C:  Severe atypical HUS caused by CFH S1191L – case presentation and review of treatment options.  Pediatr. Nephrol., 2010: 25: 1: 97-104.  SRI

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: 114: 20: 4538-45.  PA

Habbig S, Mihatsch MJ, Heinen S, Beck B, Emmel M, Skerka C, Kirschfink M, Hoppe B,Zipfel PF, Licht C: C3 deposition glomerulopathy due to a functional Factor H defect. Kidney Int., 2009: 75: 11: 1230-4. SRI

 Józsi M*, Licht C*, Strobel S, Zipfel SLH, Richter H, Heinen S, Zipfel PF, Skerka C: Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood, 2008: 111: 3: 1512-4. CPA

Zipfel PF, Edey M, Heinen S, Józsi M, Richter H, Misselwitz J, Hoppe B, Routledge D, Strain L,Hughes AE, Goodship JA, Licht C, Goodship THJ, Skerka C: Deletion of complement Factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. PLoS Genet., 2007: 3: 3: e41: 387-92. C

Licht C*, Heinen S*, Józsi M, Löschmann I, Saunders RE, Perkins SJ, Waldherr R, Skerka C, Kirschfink M, Hoppe B, Zipfel PF: Deletion of Lys224 in regulatory domain 4 of Factor H reveals a novel pathomechanism for dense deposit disease (MPGN II). Kidney Int., 2006: 70: 1: 42-50. PA