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About Sickkids
About SickKids

Eyal Grunebaum, MD

The Hospital for Sick Children
Staff Physician
Blood and Marrow Transplant Program

Director Paediatric Clinical Immunology & Allergy Residency Program
Immunology & Allergy

Head
Immunology & Allergy

Research Institute
Senior Scientist
Developmental & Stem Cell Biology

University of Toronto
Associate Professor
Department of Paediatrics

Associate Member
Institute for Medical Sciences

Chair Positions

The Canadian Society of Allergy and Clinical Immunology
Immunology section, 2006 - 2008

The Hospital for Sick Children
Animal Care Committee, 2012


Phone: 416-813-7654 ext 201320
Fax: 416-813-8624
e-mail: eyal.grunebaum@sickkids.ca

Brief Biography

  • Staff in the Division of Immunology/Allergy & Bone Marrow Transplantation
    The Hospital for Sick Children
    Toronto, Canada. 2002.
  • Fellowship in Allergy and Clinical Immunology
    The Hospital for Sick Children.
    Toronto, Canada. 1998-2001.
  • Masters in Paediatrics
    Sackler Faculty of Medicine
    Tel-Aviv University. 1998.
  • Paediatric Residency
    Hasharon Hospital and Schneider Children Medical Center.
    Israel. 1992 - 1998.
  • M.D. Hadassah Medical School, Hebrew University
    Jerusalem, Israel. 1988.
  • B.Sc. Hadassah Medical School, Hebrew University
    Jerusalem, Israel. 1983.

Clinical Care Activities

  • Diagnosis and treatment of patients suffering from primary immunodeficiency diseases, including patients with hypo-gammaglobulinemia, common variable immunodeficiency and DiGeorge syndrome
  • Management of patients undergoing bone marrow transplantation for primary immunodeficiency or hematology/oncology diseases.
  • Long-term follow up and treatment of patients with primary immune deficiencies who received hematopoietic stem cell transplantation

Research Interests

  • Using murine models and human induced pluripotent stem cells of immune deficiency, including Purine Nucleoside Phosphorylase and Adenosine Deaminase deficiency to better understand normal immune, lung and brain development.
  • Investigating various immune and non-immune abnormalities associated with inherited adenosine deaminase and purine nucleoside phosphorylase defects.
  • Studying the effect of supplementing missing enzymes by exogenous means.  My research is focused on the ability of short peptides, called "Protein-Transduction Domain" to efficiently deliver PNP and ADA into the cells and across the blood-brain barrier of PNP and ADA deficient mice. 
  • Evaluating the ability of Lenti-virus based vectors that contain PNP to integrate into murine hematopoietic stem cells derived from the PNP-deficient mice.

Research Activities

My research is related to the diagnosis and treatment of individuals born with a defect in their immune system. They are susceptible to significant infections which may be lethal. In severe cases, children could survive only if they were kept in a “bubble” or if they received new immune cells through a bone marrow transplant from a genetically identical brother or sister. Recently we showed that stem cell transplantation from other sources is also successful, although further improvement is required.

Utilizing the ability of viruses to enter cells and introduce genes into the human genome, researchers were able to replace some of the abnormal genes that cause defects in the immune system. Similarly, I am developing gene therapy for an immunodeficiency disease called purine nucleoside phosphorylase (PNP) deficiency. I am also studying factors that influence hematopoietic stem cells differentiation into T-lymphocytes which are crucial for successful cells or gene therapy in PNP deficiency, other forms of immune deficiency and several genetic diseases including those that affect the lungs, blood and malignancies.

Another field I am investigating is the ability to deliver missing proteins into human cells such as the thymus, liver and brain. My lab has shown that repeated injections of PNP enzyme attached to a protein transduction domain correct the abnormalities of PNP-deficient mice. We hope that this research may pave the way for delivering other enzymes, antibiotics and medications into cells and tissues that previously were difficult to access.

Future Research Interests

  • Identify factors that affect hematopoietic and lymphoid development.
  • Optimize conditions for successful gene therapy.
  • Establish safe and efficient gene therapy in children.

External Funding

  • 2012-2014:  An open label, single arm, historically controlled multi-center phase III study to evaluate the safety, efficacy, and pharmacokinetics.  GreenCross.
  • 2012-2015:  PNP deficiency - a multicenter study.  Jeffrey Modell Foundation.
  • 2011-2012:  Contribution of T-cell dysregulation to the development of food allergy.  Development of an animal model.
  • 2012-2014:  T-cell dysregulation in allergy.  SickKids Foundation.

Publications

For a complete list of publications, please see PubMed

Manson D, Diamond L, Oudjhane K, Hussain FB, Roifman C, Grunebaum E. (2013) Characteristic scapular and rib changes on chest radiographs of children with ADA deficiency SCIDS in the first year of life. Pediatric Radiology. 43(5):589-92.

Hassan A, Booth C, Brightwell A, Allwood Z, Veys P, Rao K, Gennery A, Slatter M, Bredius R, Finocchi A, Cancrini C, Aiuti A, Porta F, Ridella M, Steward C, Filipovich A, Marsh R, Bordon V, Almuhsen S, Al-Mousa H, Alsum Z, Al-Dekri H, Al Ghonaium A  Speckmann C, Fischer A, Mahlaoui N, Nichols KE, Grunebaum E, Al Zaharani D, Roifman CM, Honig M, Friedrich W, Boelens J, Davies EG, Cavazzana-Calvo M, Notarangelo L, Gaspar BH. (2012) Outcome of Haematopoietic Stem Cell Transplantation for Adenosine Deaminase Deficient Severe Combined Immunodeficiency. Blood 120(17):3615-15.

Roifman CM, Somech R, Kavadas F, Pires L, Nahum A, Dalal I, Grunebaum E. (2012) Defining combined immunodeficiency. Journal of Allergy Clinical Immunology 130 (1): 177-83. 

Mansouri A, Min W, Cole CJ, Josselyn SA, Henderson JT, vanEede M, Henkelman RM, Ackerley C, Grunebaum E, Roifman CM. (2012) Cerebellar abnormalities in purine nucleoside phosphorylase deficient mice. (2012) Neurobiology of Disease 47(2): 201- 9.   

Grunebaum E, Cutz E, Roifman CM. (2012) Pulmonary alveolar proteinosis in patients with adenosine deaminase deficiency. Journal of Allergy and Clinical Immunology. Journal of Allergy and Clinical immunology 29:1588-93.

Papinazath T, Min W, Suntharalingam S, Cohen A, Roifman CM, Grunebaum E. (2011) Effects of purine nucleoside posphorylase deficiency on thrymocyte development. Journal of Allergy and Clinical Immunology 128(4):854-863.

Grunebaum E, Chung CTS, DadiH , Kim P, Brigida I, Ferrua F, Cicalese MP, Aiuti A, Roifman CM. (2011) Purine metabolism, immune reconstitution and abdominal adipose tumor after gene therapy for adenosine deaminase deficiency. Journal of Allergy and Clinical Immunology 127(6):1417-9. 

Al-Sukaiti N, Reid B, Lavi S, Al-Zaharani D, Atkinson A, Roifman CM, Grunebaum E. (2010) Safety and efficacy of MMR vaccine in patients with  DiGeorge syndrome. Journal of Allergy and Clinical Immunology 126(4):868-9.

Yu Y, Arora A, Min W, Roifman CM, Grunebaum E. (2009) EdU incorporation is an alternative non-radioactive assay to [(3)H]thymidine uptake for in vitro measurement of mice T-cell proliferations.  Journal of Immunological Methods 350(1-2):29-35.

Sauer AV, Mrak E, Hernandez RJ, Zacchi E, Cavani F, Casiraghi M, Grunebaum E, Roifman CM, Cervi MC, Ambrosi A, Carlucci F, Roncarolo MG, Villa A, Rubinacci A, Aiuti A. (2009) Adenosine deaminase deficiency results in a bone phenotype characterized by RANKL/OPG imbalance and osteoblasts insufficiency.  Blood 114(15):3216-26.

Liao P, Toro A, Min W, Lee S, Roifman CM, Grunebaum E. (2008) Lentivirus gene therapy for purine nucleoside phosphorylase deficiency. Journal of Gene Medicine 10(12):1282-93.  

Grunebaum E, Bates A, Roifman CM. (2008) Omenn syndrome is associated with mutations in DNA ligase IV. Journal of Allergy and Clinical Immunology 122(6):1219-20.

Roifman CM, Somech R, Grunebaum E. (2008 Matched unrelated bone marrow transplant for T+ combined immunodeficiency. Bone Marrow Transplant 41(11):947-52.

Nofech-Mozes Y, Blaser SI, Kobayashi J, Grunebaum E, Roifman CM. (2007) Neurologic abnormalities in patients with adenosine deaminase deficiency. Pediatric Neurology 37:218-21.

Toro A, Grunebaum E. (2006) TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice. Journal of Clinical Investigation 116(10):2717-26.

Toro A, Paiva M, Ackerley C, Grunebaum E. (2006) Intracellular delivery of purine nucleoside phosphorylase (PNP) fused to protein transduction domain corrects PNP deficiency in vitro. Cellular Immunology 240(2):107-15.

Grunebaum E, Sharfe N, Roifman CM. (2006) Human T cell immunodeficiency: when signal transduction goes wrong. Immunologic Research 35(1-2):117-26.

Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B, Notarangelo LD, Roifman CM. (2006) Bone marrow transplant from matched unrelated donors in severe combined immune deficiency. Journal of American Medical Association. 295:508-518.