Maria Grazia Roncarolo lab

Maria Grazia Roncarolo's lab leads efforts to translate scientific discoveries in genetic diseases and regenerative medicine into novel patient therapies, including treatments based on stem cells and gene therapy.Dr. Roncarolo, a pediatric immunologist by training, spent her early career in Lyon, France, where she focused on severe inherited metabolic and immune diseases, including severe combined immunodeficiency (SCID), better known as “bubble boy disease.” Dr. Roncarolo was a key member of the team that carried out the first stem cell transplants given before birth to treat these genetic diseases.

While studying inherited immune diseases, Dr. Roncarolo discovered a new class of T cells. These cells, called T regulatory type 1 cells, help maintain immune-system homeostasis by, among other things, preventing autoimmune diseases and helping the immune-system tolerate transplanted cells and organs. Recently, she completed the first clinical trial using T regulatory type 1 cells to prevent severe graft-versus-host disease in leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.
Dr. Roncarolo worked for several years at DNAX Research Institute for Molecular and Cellular Biology in Palo Alto, where she contributed to the discovery of novel cytokines and she studied the role of cytokines in induction of tolerance and in promotion of stem cell growth and differentiation.
Dr. Roncarolo developed new gene-therapy approaches, which she pursued as director of the Telethon Institute for Cell and Gene Therapy at the San Raffaele Scientific Institute in Milan. She was the principal investigator leading the successful gene therapy trial for SCID patients lacking adenosine deaminase (ADA), a severe life-threatening disorder. The trial is now considered the gold standard for gene therapy in inherited immune diseases. Under her direction, the Institute has been seminal in showing the efficacy of gene therapy for other untreatable inherited metabolic diseases and primary immunodeficiencies. 
Dr. Roncarolo’s goal at Stanford is to build the teams and infrastructures to fast track stem cell and gene therapy to the clinic and to bring basic-science discoveries to patients. In addition, her laboratory continues to work on T regulatory cell-based treatments to induce tolerance after transplantation of allogeneic tissue stem cells. She recently published in Nature Medicine new biomarkers for T regulatory type 1 cells, which will be used to purify the cells and to track them in patients. She is also investigating genetic chronic inflammatory and autoimmune diseases due to impairment in T regulatory cell functions.

Professor of Pediatrics (Stem Cell Transplantation) and of Medicine (Blood and Marrow Transplantation)
(650) 498-0297


  • APVO210: A Bispecific Anti-CD86-IL-10 Fusion Protein (ADAPTIR (TM)) to Induce Antigen-Specific T Regulatory Type 1 Cells FRONTIERS IN IMMUNOLOGY Pellerin, L., Chen, P., Gregori, S., Hernandez-Hoyos, G., Bacchetta, R., Roncarolo, M. 2018; 9
  • Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety MOLECULAR THERAPY Cicalese, M., Ferrua, F., Castagnaro, L., Rolfe, K., De Boever, E., Reinhardt, R. R., Appleby, J., Roncarolo, M., Aiuti, A. 2018; 26 (3): 917–31


    Loss of adenosine deaminase activity leads to severe combined immunodeficiency (ADA-SCID); production and function of T, B, and natural killer (NK) cells are impaired. Gene therapy (GT) with an autologous CD34+-enriched cell fraction that contains CD34+ cells transduced with a retroviral vector encoding the human ADA cDNA sequence leads to immune reconstitution in most patients. Here, we report short- and medium-term safety analyses from 18 patients enrolled as part of single-arm, open-label studies or compassionate use programs. Survival was 100% with a median of 6.9 years follow-up (range, 2.3 to 13.4 years). Adverse events were mostly grade 1 or grade 2 and were reported by all 18 patients following GT. Thirty-nine serious adverse events (SAEs) were reported by 15 of 18 patients; no SAEs were considered related to GT. The most common adverse events reported post-GT include upper respiratory tract infection, gastroenteritis, rhinitis, bronchitis, oral candidiasis, cough, neutropenia, diarrhea, and pyrexia. Incidence rates for all of these events were highest during pre-treatment, treatment, and/or 3-month follow-up and then declined over medium-term follow-up. GT did not impact the incidence of neurologic/hearing impairments. No event indicative of leukemic transformation was reported.

    View details for DOI 10.1016/j.ymthe.2017.12.022

    View details for Web of Science ID 000427911800026

    View details for PubMedID 29433935

    View details for PubMedCentralID PMC5910668

  • Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Barzaghi, F., Hernandez, L., Neven, B., Ricci, S., Kucuk, Z., Bleesing, J. J., Nademi, Z., Slatter, M., Ulloa, E., Shcherbina, A., Roppelt, A., Worth, A., Silva, J., Aiuti, A., Murguia-Favela, L., Speckmann, C., Carneiro-Sampaio, M., Fernandes, J., Baris, S., Ozen, A., Karakoc-Aydiner, E., Kiykim, A., Schulz, A., Steinmann, S., Notarangelo, L., Gambineri, E., Lionetti, P., Shearer, W., Forbes, L. R., Martinez, C., Moshous, D., Blanche, S., Fisher, A., Ruemmele, F. M., Tissandier, C., Ouachee-Chardin, M., Rieux-Laucat, F., Cavazzana, M., Qasim, W., Lucarelli, B., Albert, M. H., Kobayashi, I., Alonso, L., De Heredia, C., Kanegane, H., Lawitschka, A., Seo, J., Gonzalez-Vicent, M., Diaz, M., Goyal, R., Sauer, M. G., Yesilipek, A., Kim, M., Yilmaz-Demirdag, Y., Bhatia, M., Khlevner, J., Padilla, E., Martino, S., Montin, D., Neth, O., Molinos-Quintana, A., Valverde-Fernandez, J., Broides, A., Pinsk, V., Ballauf, A., Haerynck, F., Bordon, V., Dhooge, C., Garcia-Lloret, M., Bredius, R. G., Kawak, K., Haddad, E., Seidel, M., Duckers, G., Pai, S., Dvorak, C. C., Ehl, S., Locatelli, F., Goldman, F., Gennery, A., Cowan, M. J., Roncarolo, M., Bacchetta, R., PIDTC, IEWP, European Soc Blood Marrow 2018; 141 (3): 1036-+


    Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS.Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.

    View details for DOI 10.1016/j.jaci.2017.10.041

    View details for Web of Science ID 000426974800024

    View details for PubMedID 29241729

  • Identity and Diversity of Human Peripheral Th and T Regulatory Cells Defined by Single-Cell Mass Cytometry JOURNAL OF IMMUNOLOGY Kunicki, M. A., Hernandez, L., Davis, K. L., Bacchetta, R., Roncarolo, M. 2018; 200 (1): 336–46


    Human CD3+CD4+ Th cells, FOXP3+ T regulatory (Treg) cells, and T regulatory type 1 (Tr1) cells are essential for ensuring peripheral immune response and tolerance, but the diversity of Th, Treg, and Tr1 cell subsets has not been fully characterized. Independent functional characterization of human Th1, Th2, Th17, T follicular helper (Tfh), Treg, and Tr1 cells has helped to define unique surface molecules, transcription factors, and signaling profiles for each subset. However, the adequacy of these markers to recapitulate the whole CD3+CD4+ T cell compartment remains questionable. In this study, we examined CD3+CD4+ T cell populations by single-cell mass cytometry. We characterize the CD3+CD4+ Th, Treg, and Tr1 cell populations simultaneously across 23 memory T cell-associated surface and intracellular molecules. High-dimensional analysis identified several new subsets, in addition to the already defined CD3+CD4+ Th, Treg, and Tr1 cell populations, for a total of 11 Th cell, 4 Treg, and 1 Tr1 cell subsets. Some of these subsets share markers previously thought to be selective for Treg, Th1, Th2, Th17, and Tfh cells, including CD194 (CCR4)+FOXP3+ Treg and CD183 (CXCR3)+T-bet+ Th17 cell subsets. Unsupervised clustering displayed a phenotypic organization of CD3+CD4+ T cells that confirmed their diversity but showed interrelation between the different subsets, including similarity between Th1-Th2-Tfh cell populations and Th17 cells, as well as similarity of Th2 cells with Treg cells. In conclusion, the use of single-cell mass cytometry provides a systems-level characterization of CD3+CD4+ T cells in healthy human blood, which represents an important baseline reference to investigate abnormalities of different subsets in immune-mediated pathologies.

    View details for DOI 10.4049/jimmunol.1701025

    View details for Web of Science ID 000418271200032

    View details for PubMedID 29180490

  • gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO molecular medicine Aiuti, A., Roncarolo, M. G., Naldini, L. 2017; 9 (6): 737-740

    View details for DOI 10.15252/emmm.201707573

    View details for PubMedID 28396566