Researcher

    Massimiliano Paganelli , M.D. , Ph.D.

    m.paganelli@umontreal.ca
    Massimiliano Paganelli
    Research Axis
    Metabolic and Cardiovascular Health Axis
    Research Theme
    Pediatric gastro-intestinal and liver diseases
    Address
    CHUSJ - Centre de Recherche

    Phone
    514 345-4931 #4278

    Fax
    514 345-4999

    Title

    • Assistant Professor, Department of Pediatrics, Université de Montréal (2015)
    • Pediatric Gastroenterologist/Hepatologist, CHU Sainte-Justine (2015)

    Education

    • Fellowship in pediatric gastroenterology, CHU Sainte-Justine, Université de Montréal, 2012-2014 
    • PhD in hepatology and cell therapy, Université catholique de Louvain, Brussels, Belgium, 2009-2012 
    • Fellowship in pediatric hepatology, Cliniques Saint-Luc, Université catholique de Louvain, Brussels, 2008-2010 
    • Residency in pediatrics, University of Rome «La Sapienza», Rome, Italy, 2005-2010 
    • Fellowship in pediatric hepatology, Université de Naples «Federico II», Naples, Italy, 2004-2005 
    • MD, University of Rome «La Sapienza», Rome, Italy, 1998-2004

    Career Summary

    Massimiliano Paganelli did his medical studies at the University of Rome “La Sapienza”. He started caring for children with liver diseases in 2005 during his first fellowship in pediatric hepatology at the University of Naples “Federico II”. During his training in pediatrics at “La Sapienza” university, Dr Paganelli cultivated such an interest in gastrointestinal and liver diseases of children with an intense clinical and research activity in one of the leading specialized department in Europe.  He then moved to Brussels for 18 months of subspecialty training in hepatology and liver transplantation at Cliniques Saint-Luc in Brussels (a pioneer center for pediatric liver transplantation). In Brussels, Dr Paganelli started focusing on liver cell transplantation and cell therapy for liver diseases. He did a PhD in pediatric hepatology and cell therapy at the Université catholique de Louvain, working on in vitro differentiation of stem cells to hepatocytes, in vitro disease modeling with stem cells-derived hepatocytes, cell therapy for inborn errors of liver metabolism. His researches led to several prizes, presentations at international meetings and scientific publications. Subsequently Dr Paganelli refined his clinical training with a fellowship in pediatric gastroenterology and nutrition at CHU Sainte-Justine, where he was recruited to continue his clinical activity as pediatric gastroenterologist/hepatologist (with a special focus on liver transplantation) and carry on his research on the use of stem cells for the treatment of liver diseases.

    Research Interests

    Dr Paganelli’s research aims at treating liver diseases by the means of cellular therapy. His lab generates induced pluripotent stem (iPS) cells from the blood of patients with liver diseases in order to achieve the following objectives:

    1. In vitro differentiation to hepatocyte-like cells and establishment of cellular models of the different diseases. Such models are used to study the pathophysiology of the disease, try new treatments, and assess the effect of known drugs in order to predict in vivo response (personalized medicine).
    2. Genome editing by CRISPR/Cas9 technology to correct the disease-causing mutation (for inborn errors of liver metabolism), with subsequent expansion of the corrected population, differentiation to hepatocyte-like cells and transplantation. Such an approach aims at restoring the deficient function eliminating the need for liver transplantation.
    3. Generation of liver organoids with tridimensional structure and function comparable to the human liver. Such liver buds will be created from corrected iPS obtained from patients with metabolic liver disease. Once their creation protocol and culture conditions improved and their safety proven, liver organoids might be transplanted to patients to replace their diseased liver.

    The projects currently ongoing in the lab imply the study of iPS cells-to-hepatocyte differentiation process, the creation and validation of an in vitro model of hereditary tyrosinemia type I, the correction of the disease-causing mutation in such a model, the assessment of the efficacy and safety of the transplantation of hepatocytes derived form corrected iPS cells in a tyrosinemia mouse model.

    Dr Paganelli takes part in several clinical studies on liver diseases he is confronted with in the daily practice, with a special interest for liver transplantation, neonatal cholestasis and chronic hepatitis B. 

    Research Topics

    1. Generation of iPS cells from the blood of patients with liver disease.
    2. Differentiation of stem cells from several origins to hepatocytes, and assessment of the differentiation quality.
    3. Creation of in vitro models of several liver diseases using stem cells-derived hepatocytes.
    4. Cell transplantation in several mouse models of liver diseases.
    5. Generation of liver organoids with iPS cells obtained from patients with liver disease.
    6. Clinical research on neonatal cholestasis, chronic hepatitis B and liver transplantation. 

    Awards and Distinctions

    • Clinical fellowship, Departement of Pediatrics, Université de Montréal (2012-2013) 
    • Doctoral fellowship, IREC, Université catholique de Louvain (2011-2012) 
    • Grant for a scientific stay, Fonds National de la Recherche Scientifique Belge (2009-2010) 
    • «Charlotte Anderson» Young Investigator 2009, European Society for Pediatric Gastroenterology, Hepatology and Nutrition - ESPGHAN (2009)
    • Research fellowship, Departement of Pediatrics, University of Rome «La Sapienza» (2005)

    Publications

    1. Paganelli M, Stephenne X, Sokal EM.Chronic hepatitis B in children and adolescents. J Hepatol 2012;57:885-896.
    2. Paganelli M, Dallmeier K, Nyabi O, Scheers I, Kabamba B, Neyts J, Goubau P, Najimi M, Sokal EM. Differentiated umbilical cord matrix stem cells as a new in vitro model to study early events during HBV infection. Hepatology 2013;57:59-69.
    3. Sokal E*, Paganelli M*, Wirth S, Vajro P, Lacaille F, Kelly D, Mieli-Vergani G. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines. J Hepatol 2013;59:814-829.
    4. Scheers I, Lombard C, Paganelli M, Campard D, Najimi M, Gala JL, Decottignies A, Sokal E. Human umbilical cord matrix stem cells maintain multilineage differentiation abilities and do not transform during long-term culture. PLoS One 2013;8(8):e71374.
    5. Paganelli M, Nyabi O, Brice S, Evraerts J, El Malmi I, Heremans Y, Dollé L, Benton C, Buc-Calderon P, van Grunsven L, Heimberg H, Campard D, Sokal E, Najimi M. Down regulation of Sox9 expression associates with hepatogenic differentiation of human liver mesenchymal stem/progenitor cells. Stem Cells Dev 2014;23(12):1377-1391.
    6. Paganelli M, Beaunoyer M, Samson Y, Dal Soglio D, Dubois J, Lallier M, Alvarez F. A child with unresectable biliary rhabdomyosarcoma: 48-month disease-free survival after liver transplantation. Pediatr Transplant 2014;18(5):e146-51.
    7. Paganelli M, Alvarez F, Halac U. Use of hemospray for non-variceal esophageal bleeding in an infant. J Hepatol 2014;61:712-713.
    8. Paganelli M, Patey N, Bass LM, Alvarez F. Anti-CD20 treatment for giant cell hepatitis with autoimmune hemolytic anemia. Pediatrics 2014;134(4):e1206-10.
 

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