eyal grunebaum
Eyal GrunebaumMD
Associate Professor

Contact Info

T. (416) 813-8625
F. (416) 813-8624

Location

The Hospital for Sick Children
555 University Avenue
Toronto
ON, M5G1X8

Research Interests

Adaptive Immunity, Regulatory T-cells

Accepting

Grad Students Must First Apply Through Department

Appointments

Donald & Audrey Campbell Chair of Immunology
Associate Professor of Paediatrics, University of Toronto
Head, Division of Immunology and Allergy at SickKids
Director, Pediatric Clinical Immunology and Allergy Training Program at SickKids
  • Diagnosis and management of primary immune defects
  • Stem cell development into T lineage.
  • Immune dysegulation
  • Inherited purine defects
  • Cell, protein and gene therapy
  • Enzyme replacement

Primary immune deficiency diseases (PIDD) can lead to increased susceptibility to infections, immune dysregulation and malignancy. As a clinician scientist directly managing such patients, my research focuses on improving the understanding, diagnosis and treatment of these conditions.

Research/Teaching

Research Synopsis:

1. Immune dysregulation

My lab is studying the role of specific T cells subpopulations in regulating immune responses during severe allergic reactions, autoimmunity and exaggerated inflammation such as that observed among patients with Omenn’s syndrome [1,2] or following cell and organ transplantations.

2. Hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantations (HSCT) have been used to treat many patients suffering from severe PIDD. We demonstrated that HSCT using HLA-matched unrelated donors result in better survival and immune reconstitution than HSCT using haplo-identical parents [3,4]. Currently my lab is investigating the best preparation for HSCT (myeloablative versus non-myeloablative chemotherapy), stem cell source (bone marrow versus umbilical cord blood) and management of graft-versus host disease, which is still the main cause for morbidity and mortality after HSCT for PIDD [5,6].

3. Inherited purine defects

Inherited defects in the purine enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) account for >25% of all profound T cells deficiencies [7,8]. We have recently demonstrated that ADA- and PNP- deficiency also cause neurological, pulmonary, hepatic and bone abnormalities in children [9, 10, 11, 12]. Using relevant ADA- and PNP- deficient animal models as well as induced pleuri-potent stem cells from patients, my lab has been able to better characterize the mechanisms contributing to the multi-organ damage. Understanding the pathogenesis of these conditions has allowed us to better appreciate the effects of HSCT [13], enzyme replacement [14, 15] and gene therapy [16, 17, 18] for ADA and PNP deficiency. Indeed, recognizing the limitation of current management options and the need to correct the neurological defects led my lab to develop novel treatments that deliver the missing purine enzymes into cells and across the blood brain barrier [19, 20, 21, 22], a strategy that my lab continues to explore.

Publications and Awards

Recent Publications

  1. Grunebaum E, Bates A, Roifman CM. Omenn syndrome is associated with mutations in DNA ligase IV. J Allergy Clin Immunol. 2008 Dec;122(6):1219-20.
  2. Roifman CM, Zhang J, Atkinson A, Grunebaum E, Mandel K. Adenosine deaminase deficiency can present with features of Omenn syndrome. J Allergy Clin Immunol. 2008;121(4):1056-8.
  3. Grunebaum E, Mazzolari E, Porta F, Dallera D, Atkinson A, Reid B, Notarangelo LD, Roifman CM. Bone marrow transplantation for severe combined immune deficiency. JAMA. 2006 Feb 1;295(5):508-18.
  4. Marcus N, Takada H, Law J, Cowan MJ, Gil J, Regueiro JR, Plaza Lopez de Sabando D, Lopez-Granados E, Dalal J, Friedrich W, Manfred H, Hanson IC, Grunebaum E, Shearer WT, Roifman CM. Hematopoietic stem cell transplantation for CD3δ deficiency. J Allergy Clin Immunol. 2011 Nov;128(5):1050-7.
  5. Somech R, Kavadas FD, Atkinson A, Grunebaum E, Roifman CM. High-dose methylprednisolone is effective in the management of acute graft-versus-host disease in severe combined immune deficiency. J Allergy Clin Immunol. 2008 Dec;122(6):1215-6.
  6. Bulley SR, Benson L, Grunebaum E, Roifman CM. Cardiac chamber hypertrophy following hematopoietic stem cell transplantation for primary immunodeficiency. Biol Blood Marrow Transplant. 2008 Feb;14(2):229-35.
  7. Grunebaum E, Cohen A, Roifman CM. Recent advances in understanding and managing adenosine deaminase and purine nucleoside phosphorylase deficiencies. Curr Opin Allergy Clin Immunol. 2013 Dec;13(6):630-8.
  8. Somech R, Lev A, Grisaru-Soen G, Shiran SI, Simon AJ, Grunebaum E. Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency. Immunol Res. 2013 May;56(1):150-4.
  9. Nofech-Mozes Y, Blaser SI, Kobayashi J, Grunebaum E, Roifman CM. Neurologic abnormalities in patients with adenosine deaminase deficiency. Pediatr Neurol. 2007 Sep;37(3):218-21.
  10. Grunebaum E, Cutz E, Roifman CM. Pulmonary alveolar proteinosis in patients with adenosine deaminase deficiency. J Allergy Clin Immunol. 2012 Jun;129(6):1588-93.
  11. Somech R, Lai YH, Grunebaum E, Le Saux N, Cutz E, Roifman CM. Polyethylene glycol-modified adenosine deaminase improved lung disease but not liver disease in partial adenosine deaminase deficiency. J Allergy Clin Immunol. 2009;124(4):848-50.
  12. Manson D, Diamond L, Oudjhane K, Hussain FB, Roifman C, Grunebaum E. Characteristic scapular and rib changes on chest radiographs of children with ADA-deficiency SCIDS in the first year of life. Pediatr Radiol. 2013 Mar;43(5):589-92.
  13. Hassan A, Booth C, Brightwell A, Allwood Z, Veys P, Rao K, Hönig M, Friedrich W, Gennery A, Slatter M, Bredius R, Finocchi A, Cancrini C, Aiuti A, Porta F, Lanfranchi A, Ridella M, Steward C, Filipovich A, Marsh R, Bordon V, Al-Muhsen S, Al-Mousa H, Alsum Z, Al-Dhekri H, Al Ghonaium A, Speckmann C, Fischer A, Mahlaoui N, Nichols KE, Grunebaum E, Al Zahrani D, Roifman CM, Boelens J, Davies EG, Cavazzana-Calvo M, Notarangelo L, Gaspar HB; Inborn Errors Working Party of the European Group for Blood and Marrow Transplantation and European Society for Immunodeficiency. Outcome of hematopoietic stem cell transplantation for adenosine deaminase-deficient severe combined immunodeficiency. Blood. 2012 25;120(17):3615-24;
  14. Husain M, Grunebaum E, Naqvi A, Atkinson A, Ngan BY, Aiuti A, Roifman CM. Burkitt's lymphoma in a patient with adenosine deaminase deficiency-severe combined immunodeficiency treated with polyethylene glycol-adenosine deaminase. J Pediatr. 2007 Jul;151(1):93-5.
  15. Dhanju R, Min W, Ackerley C, Cimpean L, Palaniyar N, Roifman CM, Grunebaum E. Pulmonary alveolar proteinosis in adenosine deaminase-deficient mice. J Allergy Clin Immunol. 2014 Jan 15.
  16. Grunebaum E, Chung CT, Dadi H, Kim P, Brigida I, Ferrua F, Cicalese MP, Aiuti A, Roifman CM. Purine metabolism, immune reconstitution, and abdominal adipose tumor after gene therapy for adenosine deaminase deficiency. J Allergy Clin Immunol. 2011 Jun;127(6):1417-9.e3.
  17. 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. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency. Blood. 2009 Oct 8;114(15):3216-26.
  18. Liao P, Toro A, Min W, Lee S, Roifman CM, Grunebaum E. Lentivirus gene therapy for purine nucleoside phosphorylase deficiency. J Gene Med. 2008;10(12):1282-93.
  19. Toro A, Paiva M, Ackerley C, Grunebaum E. Intracellular delivery of purine nucleoside phosphorylase (PNP) fused to protein transduction domain corrects PNP deficiency in vitro. Cell Immunol. 2006 Apr;240(2):107-15.
  20. Toro A, Grunebaum E. TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice. J Clin Invest. 2006 Oct;116(10):2717-26.
  21. Papinazath T, Min W, Sujiththa S, Cohen A, Ackerley C, Roifman CM, Grunebaum E. Effects of purine nucleoside phosphorylase deficiency on thymocyte development. J Allergy Clin Immunol. 2011 Oct;128(4):854-863.
  22. Mansouri A, Min W, Cole CJ, Josselyn SA, Henderson JT, van Eede M, Henkelman RM, Ackerley C, Grunebaum E, Roifman CM. Cerebellar abnormalities in purine nucleoside phosphorylase deficient mice. Neurobiol Dis. 2012 Aug;47(2):201-9.
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