Maria Grazia Roncarolo, MD, Professor, Departments of Pediatrics and Medicine, Stanford University School of Medicine
Research Description: A main 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. N. Gagliani, S. Gregori, T. Jofra, A. Valle, A. Stabilini, D.M. Rothstein, M. Atkinson, M.G. Roncarolo, and M. Battaglia (2011). Rapamycin combined with anti-CD45RB mAb and IL-10 or with G-CSF induces tolerance in a stringent mouse model of islet transplantation. PLoS One 6: e 28434.
2. H. Rodriguez, W.E. Russell, D. Schatz, D. Wherrett, D.M. Wilson, J.P. Krischer, J.S. Skyler, and Type 1 Diabetes TrialNet Abatacept Study Group (including M.G. Roncarolo) (2011). Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. The Lancet 378: 412-419.
3. D.K. Wherrett, B. Bundy, D.J. Becker, L.A. DiMeglio, S.E. Gitelman, R. Goland, P.A. Gottlieb, C.J. Greenbaum, K.C. Herold, J.B. Marks, …, J.P. Palmer, P. Raskin, H. Rodriguez, D. Schatz, D.M. Wilson, J.P. Krischer, J.S. Skyler, and Type 1 Diabetes TrialNet GAD Study Group (including M.G. Roncarolo) (2011). Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. The Lancet 378: 319-327.
4. L. Yu, D.C. Boulware, C.A. Beam, J.C. Hutton, J.M. Wenzlau, C.J. Greenbaum, P.J. Bingley, J.P. Krischer, J.M. Sosenko, J.S. Skyler, G.S. Eisenbarth, J.M. Mahon and Type 1 Diabetes TrialNet Study Group (including M.G. Roncarolo) (2012). Zinc transporter-8 autoantibodies improve prediction of type 1 diabetes in relatives positive for the standard biochemical autoantibodies. Diabetes Care 35: 1213-1218.
5. N. Gagliani, T. Jofra, A. Valle, A. Stabilini, C. Morsiani, S. Gregori, S. Deng, D.M. Rothstein, M. Atkinson, M. Kamanaka, R.A. Flavell, M.G. Roncarolo, and M. Battaglia (2013). Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. Am J Transplant 13: 1963-1975.
6. M. Akbarpour, K.S. Goudy, A. Cantore, F. Russo, F. Sanvito, L. Naldini, A. Annoni, M.G. Roncarolo (2015). Insulin B chain 9-23 gene transfer to hepatocytes protects from type 1 diabetes by inducing Ag-specific FoxP3+ Tregs. Sci Transl Med. 2015 May 27;7(289):289ra81.