Maria Roncarolo

Maria Grazia Roncarolo, MD, George D. Smith Professor, Department of Pediatrics, Division of Stem Cell and Regenerative Medicine; Professor, Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University School of Medicine

Research Description: A major focus of Dr. Roncarolo’s research has been investigating the mechanisms underlying the pathology of genetic and acquired auto-immune diseases such as Wiskott Aldrich Syndrome (WAS), the IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy X-linked), inflammatory bowel diseases, celiac disease and type 1 diabetes. She discovered that patients with WASP deficiency have a defect in the immunological synapse and an impaired differentiation of CD25+FOXP3+ T regulatory cells. She led the studies on IPEX patients showing defective regulatory and effector functions in patients with different FOXP3 mutations. She demonstrated that treatment with rapamycin and IL-10 restores tolerance in preclinical models of type 1 diabetes and pancreatic islet transplantation by inducing expansion of CD25+FOXP3+ regulatory cells in the tissue and promoting differentiation of T regulatory type 1 (Tr1) cells in the spleen. She established a preclinical in vivo gene therapy protocol using hepatocyte lentiviral vector targeted deliver of insulin peptides, to protect and reverse type 1 diabetes. She showed that cell therapy with polyclonal or antigen specific Tr1 cells prevents pancreatic islet rejection, and her current focus is on studies to achieve long-term normoglycemia and immunological tolerance in type 1 diabetes.

Selected relevant publications (Stanford DRC members in BOLD):

  1. Sato Y, Passerini L, Piening BD, Uyeda MJ, Goodwin M, Gregori S, Snyder MP, Bertaina A, Roncarolo MG, Bacchetta R. Human-engineered Treg-like cells suppress FOXP3-deficient T cells but preserve adaptive immune responses in vivo. Clin Transl Immunology. 2020 Nov 25;9(11):e1214. doi: 10.1002/cti2.1214. PMID: 33304583; PMCID: PMC7688376. 

  2. Russo F, Citro A, Squeri G, Sanvito F, Monti P, Gregori S, Roncarolo MG, Annoni A. InsB9-23 Gene Transfer to Hepatocyte-Based Combined Therapy Abrogates Recurrence of Type 1 Diabetes After Islet Transplantation. Diabetes. 2021 Jan;70(1):171-181. doi: 10.2337/db19-1249. PMID: 33122392. 

  3. Wiebking V, Lee CM, Mostrel N, Lahiri P, Bak R, Bao G, Roncarolo MG, Bertaina A, Porteus MH. Genome editing of donor-derived T-cells to generate allogenic chimeric antigen receptor-modified T cells: Optimizing αβ T cell-depleted haploidentical hematopoietic stem cell transplantation. Haematologica. 2020 Apr 2:haematol.2019.233882. doi: 10.3324/haematol.2019.233882. PMID: 32241852.