Clinical studies


Alagille syndrome

Alagille syndrome (ALGS) is a multisystem autosomal dominant disorder characterized by bile duct paucity and associated syndromic features. The syndromic features are classically defined by the presence of three of five major clinical criteria: cholestatic liver disease, cardiac disease, ocular abnormalities (typically posterior embryotoxon), skeletal abnormalities (most commonly butterfly vertebrae), and characteristic facial features. We have described vascular and renal anomalies as additional disease-defining clinical features.

ALGS is a rare condition and affects between 1:30,000 to 1:70,000 individuals. ALGS is caused by mutations in one of two genes; the Notch signalling Pathway ligand JAGGED1 (in 94 per cent of patients) or the notch receptor, NOTCH2 (in 1 to 2 per cent of patients). The liver disease ranges from mild to very severe with extensive liver damage necessitating liver transplantation.

We are actively conducting clinical and translational studies of patients with Alagille syndrome.

In 2018, we launched the Global ALagille Alliance Study (GALA) in partnership with the Alagille Syndrome Alliance (ALGSA). The GALA study is a global initiative to create an international research database of clinical, genetic, and laboratory data in children and young adults with Alagille syndrome (ALGS). By pooling together available datasets, we will increase our understanding of ALGS and identify this patient population’s unique challenges and needs. The GALA Study consists of more than 100 physicians, scientists, and research coordinators from 35 countries worldwide. The Hospital for Sick Children and the University of Toronto are leading this international multi-centre study. The GALA study is generously supported by the ALGSA, The SickKids Foundation, Mirum Pharmaceuticals, Inc, and Albireo Pharma, Inc.

If you are interested in participating as a site, please don’t hesitate to contact the GALA Data Coordinating Centre at for more information.


Cholestatic liver diseases

Cholestatsis is a condition in which bile is not formed normally in the liver, or its flow from the liver to the intestine is impaired. We are a part of the Childhood Liver Disease Research Network (ChiLDReN), a National Institute of Diabetes and Digestive and Kidney Diseases-(NIDDK) supported consortium for the study and care of children with cholestatic disorders (including Alagille syndrome). ChiLDReN consists of 14 Clinical Centers in the US and Canada. We are the only Canadian site. The goal of ChiLDReN is to understand the causes of liver disease and to discover new approaches to the diagnosis and treatment of liver diseases in infants, children and young adults with cholestasis, and those who undergo liver transplantation. ChiLDReN is currently studying the following diseases:

  • Alagille syndrome
  • Alpha-1-antitrypsin deficiency
  • Bile acid synthesis and metabolism defects
  • Biliary atresia
  • Cystic fibrosis liver disease
  • Idiopathic neonatal hepatitis
  • Mitochondrial hepatopathies
  • Progressive familial intrahepatic cholestasis

We run both natural history and clinical therapy trial ChiLDReN studies at SickKids. For more information on all active ChiLDReN studies, please visit the ChiLDReN website.


Frailty is a syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems and causing vulnerability to adverse outcomes.1 Frailty is a validated measure of debilitation in the elderly, which is correlated with significant morbidity and mortality. Adult data reveal that frailty measures elements of morbidity in patients awaiting liver transplantation that are not captured in laboratory evaluations or current organ allocation scoring systems. In collaboration with Dr. Vicky Ng, we have adapted the five elements of the adult Fried frailty phenotype in children utilizing validated paediatric tools.

We have completed a pilot feasibility project to assess frailty in children and have now extended this study to a multi-site collaboration of 16 North American transplant centres, with SickKids as the lead site.

Basic research

Stem cell studies of bile duct disorders; “Biliary Disease in a Dish

In the laboratory, we study rare forms of inherited biliary disease and these studies are fundamental to understanding biliary disease mechanisms that have generalizability to other more common and complex bile duct diseases.

The liver is comprised of two cell types which arise from bipotential cells called hepatoblasts. The first, hepatocytes, account for more than 95 per cent of the cell mass, and have long been characterized and established as playing pivotal roles in physiological processes ranging from detoxification to energy storage. Cholangiocytes, which line the intrahepatic biliary tree, account for only a small fraction of the total liver. Our understanding of cholangiocyte biology and their role in biliary disease is relatively limited due to the difficulty in purifying them from tissue samples and a lack of appropriate culture conditions. This had made assessment of biliary disease, which accounts for more than half of all liver transplants in children, incredibly challenging. To date, very few treatment options outside of transplantation exist to meet this disease burden.

In collaboration with colleagues at the McEwen Regenerative Medicine Centre, we have devised a strategy to generate pure populations of cholangiocytes from both iPS and embryonic stem cells. This process takes roughly 40 days, and has opened a conducive avenue for full characterization of cholangiocyte physiology in vitro. Additionally, with the use of 3D culture, we are able to generate “cholangiod” cysts and tubules which better reflect the in vivo environment.

Using our protocol we aim to better understand both normal cholangiocyte function and contribution to a wide variety of previously enigmatic biliary disease mechanisms.


Dr. Binita Kamath

Dr. Binita Kamath was educated at Cambridge University in England and trained at several London hospitals, including Kings College Hospital. She moved to the Children’s Hospital of Philadelphia in 2000 and completed her fellowship in GI, Hepatology and Nutrition. She joined the faculty in 2006 and developed a strong interest in cholestatic liver disease, specifically Alagille syndrome. She joined the faculty at The Hospital for Sick Children (SickKids) in 2009 as a Hepatologist and Clinician-Investigator continuing to work on biliary diseases and utilizing stem cell biology to develop disease models.

Shannon Vandriel

Program Manager

Fiorella Murillo Perez

Research Associate

Desiree Vaz - Clinical research project assistant

Desiree Vaz

Clinical Research Project Assistant

Megha Manoj

Clinical Research Project Assistant

Tharsiga Gunasegaran Clinical Research Project Assistant

Tharsiga Gunasegaran

Clinical Research Project Assistant

Zune Ahmad

Zune Ahmad

Clinical Research Project Assistant

Diana Islam, Lab Manager

Diana Islam, PhD

Lab Research Project Manager

Robel Yosief, M.Sc.

Research Technologist

Rita Kumari, PhD

Postdoctoral Fellow

Qijun Zhang

Graduate Student PhD (Visiting)

Selected publications

  1. Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.
    Hansen BE, Vandriel SM, Vig P, Garner W, Mogul DB, Loomes KM, Piccoli DA, Rand EB, Jankowska I, Czubkowski P, Gliwicz-Miedzińska D, Gonzales EM, Jacquemin E, Bouligand J, D’Antiga L, Nicastro E, Arnell H, Fischler B, Sokal É, Demaret T, Siew S, Stormon M, Karpen SJ, Romero R, Ebel NH, Feinstein JA, Roberts AJ, Evans HM, Sundaram SS, Chaidez A, Hardikar W, Shankar S, Fischer RT, Lacaille F, Debray D, Lin HC, Jensen MK, Jaramillo C, Karthikeyan P, Indolfi G, Verkade HJ, Larson-Nath C, Quiros-Tejeira RE, Valentino PL, Rogalidou M, Dezsőfi A, Squires JE, Schwarz K, Calvo PL, Bernabeu JQ, Zizzo AN, Nebbia G, Bulut P, Santos-Silva E, Fawaz R, Nastasio S, Karnsakul W, Tamara ML, Busoms CM, Kelly D, Sandahl TD, Jimenez-Rivera C, Banales JM, Mujawar Q, Li LT, She H, Wang JS, Kim KM, Oh SH, Sanchez MC, Cavalieri ML, Lee WS, Hajinicolaou C, Lertudomphonwanit C, Waisbourd-Zinman O, Arikan C, Alam S, Carvalho E, Melere M, Eshun J, Önal Z, Desai DM, Wiecek S, Pinto RB, Wolters VM, Garcia J, Beretta M, Kerkar N, Brecelj J, Rock N, Lurz E, Blondet N, Shah U, Thompson RJ, Kamath BM, and The Global ALagille Alliance (GALA) Study Group.
    Manuscript Accepted by Hepatology. 
  2. Global ALagille Alliance (GALA) Study Group. Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome: Results from The GALA Study. 
    Vandriel SM, Li LT, She H, Wang JS, Gilbert MA, Jankowska I, Czubkowski P, Gliwicz-Miedzińska D, Gonzales EM, Jacquemin E, Bouligand J, Spinner NB, Loomes KM, Piccoli DA, D’Antiga L, Nicastro E, Sokal É, Demaret T, Ebel NH, Feinstein JA, Fawaz R, Nastasio S, Lacaille F, Debray D, Arnell H, Fischler B, Siew S, Stormon M, Karpen SJ, Romero R, Kim KM, Baek WY, Hardikar W, Shankar S, Roberts AJ, Evans HM, Jensen MK, Kavan M, Sundaram SS, Chaidez A, Karthikeyan P, Sanchez MC, Cavalieri ML, Verkade HJ, Lee WS, Squires JE, Hajinicolaou C, Lertudomphonwanit C, Fischer RT, Larson-Nath C, Mozer-Glassberg Y, Arikan C, Lin HC, Quintero Bernabeu J, Alam S, Kelly D, Carvalho E, Ferreira CT, Indolfi G, Quiros-Tejeira RE, Bulut P, Calvo PL, Önal Z, Valentino PL, Desai DM, Eshun J, Rogalidou M, Dezsőfi A, Wiecek S, Nebbia G, Borges Pinto R, Wolters VM, Tamara ML, Zizzo AN, Garcia J, Schwarz K, Beretta M, Sandahl TD, Jimenez-Rivera C, Kerkar N, Brecelj J, Mujawar Q, Rock N, Busoms CM, Karnsakul W, Lurz E, Santos-Silva E, Blondet N, Bujanda L, Shah U, Thompson RJ, Hansen BE, Kamath BM
    2022 Aug 29.
  3. Outcomes of Childhood Cholestasis in Alagille Syndrome: Results of a Multicenter Observational Study.
    Kamath BM, Ye W, Goodrich NP, Loomes KM, Romero R, Heubi JE, Leung DH, Spinner NB, Piccoli DA, Alonso EM, Guthery SL, Karpen SJ, Mack CL, Molleston JP, Murray KF, Rosenthal P, Squires JE, Teckman J, Wang KS, Thompson R, Magee JC, Sokol RJ; Childhood Liver Disease Research Network (ChiLDReN).
    Hepatology Communications. 2020 January 22.
  4. Systematic Review: the Epidemiology, Natural History and Burden of Alagille Syndrome.
    Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N.
    Journal of Pediatric Gastroenterology and Nutrition. 2018 Aug;67(2):148-156.
  5. Frailty in Children with Liver Disease: A Prospective Multicenter Study.
    Lurz E, Quammie C, Englesbe M, Alonso EM, Lin HC, Hsu EK, Furuya KN, Gupta NA, Venkat VL, Daniel JF, Leonis MA, Miloh T, Telega GW, Yap J, Menendez J, Book LS, Himes RW, Sundaram SS, Parekh R, Sonnenday C, Bucuvalas J, Ng VL*, Kamath BM* (* denotes equal contribution).
    Journal of Pediatrics. 2018 Mar;194:109-115.
  6. Cholangiocytes derived from induced pluripotent stem cells for disease modeling.
    Ghanekar A, Kamath BM.
    Current Opinion in Gastroenterology. (2016) May;32(3):210-215.
  7. Early life predictive markers of liver disease outcome in an International Multicentre Cohort of children with Alagille syndrome.
    Mouzaki M, Bass LM, Sokol RJ, Piccoli DA, Quammie C, Loomes KM, Heubi JE, Hertel PM, Scheenstra R, Furuya K, Kutsch E, Spinner NB, Robbins KN, Venkat V, Rosenthal P, Beyene J, Baker A, Kamath BM.
    Liver Int.
     (2016) May;36(5):755-760.
  8. Directed Differentiation of Functional Cholangiocytes from Human Pluripotent Stem Cells.
    Ogawa M, Ogawa S, Bear C, Ahmadi S, Chin S, Li B, Grompe M, Keller G*, Kamath BM*, Ghanekar A* (*denotes equal contribution).
    Nature Biotechnology. (2015) 33: pp853-861.
  9. Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome.
    Kamath BM, Chen Z, Romero R, Fredericks EM, Alonso EM, Arnon R, Heubi J, Hertel PM, Karpen SJ, Loomes KM, Murray KF, Rosenthal P, Schwarz KB, Subbarao G, Teckman JH, Turmelle YP, Wang KS, Sherker AH, Sokol RJ, Magee JC; Childhood Liver Disease Research Network (ChiLDReN).
    Journal of Pediatrics. (2015) Aug;167(2):390-396.


Thanks to the following agencies for their generous support!

Childhood Liver Disease Research Network logo


Canadian Liver Foundation logo

Canadian Liver Foundation

Alagille Syndrome Alliance logo

Alagille Syndrome Alliance

Mirum Pharmaceuticals Logo

Mirum Pharmaceuticals

Albireo Pharmaceuticals logo

Albireo Pharmaceuticals

SickKids Foundation logo

SickKids Foundation


For administrative or clinical inquiries

Kamila McClean-Samuel
Administrative Assistant

Gastroenterology, Hepatology and Nutrition
Black Wing, Room 8263
555 University Avenue
Toronto, ON M5G 1X8

416-813-6176 ext: 224845

For research inquiries

Diana Islam, PhD
Lab Research Project Manager

Developmental & Stem Cell Biology Program
SickKids Research Institute
Peter Gilgan Centre for Research and Learning
686 Bay Street,
Room 16.9400, Aisle S
Toronto, ON M5G 0A4