Education

Biography

Research Interest

Dr. Santamaria’s research focuses on the pathogenesis, immunogenetics and treatment of autoimmune disease.

Professional Activities:

Appointments and Positions:

Other Experience and Professional Memberships 

• Member, American Association for the Advancement of Science
• Member, American Association of Immunologists
• Member, Canadian Diabetes Association
• Member, Canadian Society for Immunology

Honors:

Publications

• Santamaria P, Nackleh R, Sutherland D, Barbosa J. Characterization of T lymphocytes infiltrating a human pancreas allograft affected by isletitis and recurrent diabetes.  Diabetes 41:53-61, 1992.
• Santamaria P, Boyce-Jacino M, Lindstrom A, Barbosa J, Faras A, Rich S. Class II HLA typing: direct sequencing of DRB, DQB and DQA genes.  Hum Immunol 33:69-81, 1992.
• Santamaria P, Lindstrom AL, Boyce-Jacino MT, Myster SH, Barbosa JJ, Faras AJ, Rich SS. HLA class I sequence-based typing.  Hum Immunol 37:39-50, 1993.
• Santamaria P, Utsugi T, Park P-J, Averill N, Kawazu S, Yoon J-W Beta cell-cytotoxic CD8+ T cells from non-obese diabetic mice use highly homologous T cell receptor a-chain CDR3 sequences.  J Immunol 154:2494-2503, 1995.
• Utsugi T, Yoon J-W, Park B-J, Imamura M, Averill N, Kawazu S, Santamaria P. MHC class I-restricted infiltration and destruction of pancreatic islets by NOD-mouse-derived beta cell-cytotoxic CD8+ T cell clones in vivo. Diabetes 45:1121-1131, 1996.
• Verdaguer J, Yoon J-W, Anderson B, Averill N, Utsugi T, Park B-J, Santamaria P. Acceleration of spontaneous diabetes in TCR-b-transgenic NOD mice by beta cell-cytotoxic CD8+ T cells expressing identical endogenous TCR-a chains. J Immunol 157:4726-4736, 1996.
• Schmidt D, Verdaguer J, Averill N, Santamaria P.  A mechanism for the MHC-linked resistance to autoimmunity.  J Exp Med 186:1059-1075, 1997.
• Verdaguer J, Schmidt D, Amrani A, Anderson B, Averill N, Santamaria P. Spontaneous autoimmune diabetes in monoclonal T-cell NOD Mice.  J Exp Med 186:1663-1676, 1997.
• Schmidt D, Amrani A, Verdaguer J, Bou S, Santamaria P. Autoantigen-independent deletion of diabetogenic thymocytes by protective MHC class II molecules. J Immunol, 162:4627-4636, 1999.
• Anderson B, Park B-J, Amrani A, Verdaguer J, Bou S, Santamaria P. Prevalent CD8+ T-cell response to a single peptide/Kd complex in autoimmune diabetes.  Proc Natl Acad Sci USA. 96:9311-9316, 1999.
• Amrani A, Verdaguer J, Thiessen S, Bou S, Santamaria P. IL-1α IL-1β and IFN-γ mark beta cells for Fas-dependent destruction by diabetogenic CD4+ T-lymphocytes. J Clin Invest, 105:459-468, 2000.
• Amrani A, Verdaguer J, Serra P, Tafuro S, Tan R, Santamaria P. Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature, 406:739-742, 2000.
• Amrani A, Serra P, Yamanouchi J, Trudeau J, Tan R, Elliott J, Santamaria, P. Expansion of the antigenic repertoire of a single T cell receptor upon T-cell activation, J Immunol 167:655-666, 2001.
• Liblau RS, Wong FS, Mars LT, Santamaria P. Autoreactive CD8+ T-cells in organ-specific autoimmunity: emerging targets for therapeutic intervention. Immunity, 17:1-6, 2002.
• Amrani A, Serra P, Yamanouchi J, Han B, Thiessen S, Verdaguer J, Santamaria P. CD154-dependent activation of diabetogenic CD4+ T-cells dissociated from APC activation. Immunity, 16: 719-732, 2002.
• Winer S, Tsui H, Lau A, Song A, Li X, Cheung RK, Sampson A, Afifiyan F, Elford A, Jackowski G, Becker DJ, Santamaria P, Ohashi P, Dosch HM. Autoimmune islet destruction in spontaneous type 1 diabetes is not beta-cell exclusive. Nat Med 9:198-205, 2003.
• Serra P, Amrani A, Han B, Yamanouchi J, Thiessen S, Santamaria P. RAG-dependent peripheral T cell receptor diversification in CD8+ T-lymphocytes. Proc Natl Acad Sci USA, 99:15566-15571, 2002.
• Trudeau JD, Kelly-Smith C, Verchere B, Finegood DT, Santamaria P, Tan, R. Autoreactive T cells in peripheral blood predict development of type 1 diabetes. J Clin Invest, 111:217-223, 2003.
• Lieberman SM, AM Evans, B Han, T Takaki, Y Vinnitskaya, JA Caldwell, DV Serreze, J Shabanowitz, DF Hunt, SG Nathenson, P Santamaria, T DiLorenzo. Identification of the novel  cell antigen targeted by a prevalent population of pathogenic CD8+ T cells in autoimmune diabetes.  Proc Natl Acad Sci USA, 100: 8384-8388, 2003.
• Serra P, Amrani A, Yamanouchi J,  Han, B, Thiessen S, Utsugi T, Verdaguer P, Santamaria P. CD40 ligation releases immature dendritic cells from the control of regulatory CD4+CD25+ T-cells. Immunity, 19:877-889, 2003.
• Yamanouchi J, Verdaguer J, Han B-H, Amrani A, Serra P, Santamaria P. Cross-priming of diabetogenic T-cells dissociated from CTL-induced shedding of beta cell autoantigens. J Immunol, 171:6900-6909, 2003.
• Ogasawara K, Hamerman JA, Ehrlich LR, Bour-Jordan H, Santamaria P, Bluestone JA, Lanier LL. NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity, 20:757-767, 2004.
• Moore, A., J. Grimm, B. Han, P. Santamaria. Tracking the recruitment of diabetogenic CD8+ T-cells to the pancreas in real time. Diabetes 53: 1459-1466, 2004.
• Han B, Serra P, Amrani A, Yamanouchi J, Marée AF, Edelstein-Keshet L, Santamaria P. Prevention of diabetes by manipulation of anti-IGRP autoimmunity: high efficiency of a low affinity altered peptide ligand. Nat Med, 11:645-652, 2005.
• Han B, Serra P, Yamanouchi J, Amrani A, Elliott JF, Dickie P, Dilorenzo TP, Santamaria P. Developmental control of CD8+ T-cell avidity maturation in autoimmune diabetes. J Clin Invest, 115:1879-1887, 2005.
• Tang Q, Adams JY, Tooley AJ, Bi M, Fife BT, Serra P, Santamaria P, Locksley RM, Krummel MF, Bluestone JA.  Visualizing regulatory T cell control of autoimmune response in non-obese diabetic mice. Nat Immunol, 7: 83-92, 2006.
• Maree AF, Santamaria P, Keshet LE. Modeling competition among autoreactive CD8+ T-cells in autoimmune diabetes: implications for antigen-specific therapy. Int Immunol, 18: 1067-77, 2006.
• Razavi R, Chan Y, Afifiyan FN, Liu X-J, Wan X, Yantha J, Tsui H, Tang L, Tsai S, Santamaria P, Driver JP, Serreze D, Salter MW, H-M Dosch. TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes. Cell, 127: 1123-35, 2006.
• Walter U, Santamaria P. CD8+ T-cells in autoimmunity. Curr Opin Immunol, 17: 624-631, 2006.
• Yamanouchi J, Rainbow D, Serra P, Howlett S, Hunter K, Garner VE, Gonzalez-Munoz A, Clark J, Veijola R, Cubbon R, Chen SL, Rosa R, Cumiskey AM, Serreze DV, Gregory S, Rogers J, Lyons PA, Healy B, Smink LJ, Todd JA, Peterson LB, Wicker LS, Santamaria P. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet, 39:329-337, 2007.
• Lennon GP, Bettini M, Burton AR, Vincent E, Arnold PY, Santamaria P, Vignali DA. T cell islet accumulation in type 1 diabetes is a tightly regulated, cell-autonomous event. Immunity, 31:643-653, 2009.
• Tailor P, Tsai S, Shameli A, Serra P, Wang J, Robbins S, Nagata M, Szymczak-Workman A-L, Vignali DAA, Santamaria P. The proline-rich sequence of CD3ε as an amplifier of low-avidity TCR signaling. J Immunol, 181: 243-255, 2008.
• Tsai S, Shameli A, Santamaria P. CD8+ T-cells in autoimmune diabetes. Adv Immunol 100:79-124, 2008.
• Wang J, Wicker L, Santamaria P. IL-2 and its high-affinity receptor: genetic control of immunoregulation and autoimmunity. Sem Immunol 21: 363-371, 2009.
• Yamanouchi J, Puertas MC, Verdaguer J, Lyons PA, Rainbow DB, Chamberlain G, Hunter KM, Peterson LB, Wicker LS, Santamaria P. Idd9.1 locus controls the suppressive activity of FoxP3+CD4+CD25+ regulatory T-cells. Diabetes, 59:272-281, 2010.
• Tsai S, Shameli A, Yamanouchi J, Clemente-Casares X, Wang J, Serra P, Yang Y, Medarova Z, Moore A, Santamaria P. Reversal of autoimmunity by boosting memory-like autoregulatory T-cells. Immunity, 32:568-580, 2010.
• Santamaria P. The long and winding road to understanding and conquering type 1 diabetes. Immunity 32:437-445, 2010.
• Khadra A, Tsai S, Santamaria P*, Edelstein-Keshet L*. On how monospecific memory-like autoregulatory CD8+ T cells can blunt diabetogenic autoimmunity: a computational approach. J Immunol, 185:5962-5972, 2010.
• Wang J, Tsai S, Shameli A, Yamanouchi J, Alkemade G, Santamaria P. In situ recognition of autoantigen as an essential gatekeeper in autoimmune CD8+ T cell inflammation. Proc Natl Acad Sci USA, 107:9317-22, 2010.
• Shameli A, Clemente-Casares X, Wang J, Santamaria P. Development of memory-like autoregulatory CD8+ T cells is CD4+ T cell-dependent. J Immunol, 187:2859-2866, 2011.
• Tsai S, Clemente-Casares X, Santamaria P. CD8(+) Tregs in autoimmunity: learning "self"-control from experience. Cell Mol Life Sci, 68:3781-3795, 2011.
• Tsai S, Clemente-Casares X, Santamaria P. Nanovaccines for the treatment of autoimmunity: a ‘one size’ fits all approach? J Mol Med, 89: 733-742, 2011.
• Wang J, Tsai S, Tailor P, Santamaria P. Autoantigen recognition is required for recruitment of IGRP206-214-autoreactive CD8+ T-cells but is dispensable for tolerance. J Immunol, 189: 2975-2984, 2012.
• Clemente-Casares X, Tsai S, Huang C, Santamaria P.  Antigen-specific therapeutic approaches in type 1 diabetes. In: Type 1 Diabetes. JA Bluestone, MA Atkinson, PR Arvan Editors. Cold Spring Harb Perspect Med. pages 241-263, 2012
• Cooke A, Santamaria P, Editors. Immunology and treatment of type 1 diabetes. The Rev Diabet Stud 9 (4), 2013
• Alkemade GM, Clemente-Casares X, Yu Z, Xu BY, Wang J, Tsai S, Wright JR Jr, Roep BO, Santamaria P. Local Autoantigen Expression as Essential Gatekeeper of Memory T-cell Recruitment to Islet Grafts in Diabetic Hosts. Diabetes, 62:905-911, 2013.
• Shameli A, Yamanouchi J, Tsai S, Yang Y, Clemente-Casares X, Moore A, Serra P, Santamaria P. IL-2 promotes the function of memory-like autoregulatory CD8(+) T cells but suppresses their development via FoxP3(+) Treg cells. Eur J Immunol. 43: 394-403, 2013.
• Tsai S and Santamaria P  MHC Class II Polymorphisms, Autoreactive T-Cells, and Autoimmunity. In: Antigen Presenting Cell Biology. Santambrogio L editor. Front Immunol, 4: 321, 2013.
• Tsai S, Serra P, Clemente-Casares X, Yamanouchi J, Thiessen S, Slattery RM, Elliott JF, Santamaria P. Antidiabetogenic MHC class II promotes the differentiation of MHC-promiscuous autoreactive T cells into FOXP3+ regulatory T cells. Proc Natl Acad Sci USA, 110: 3471-3476, 2013.
• Sugarman J, Tsai S, Santamaria P, Khadra A. Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy. Immunol & Cell Biol, 91: 350-359, 2013.
• Tsai S, Serra P, Clemente-Casares X, Slattery RM, Santamaria P. Dendritic Cell-Dependent In Vivo Generation of Autoregulatory T Cells by Antidiabetogenic MHC Class II. J Immunol, 191: 70-82, 2013.
• Mukherjee G, Geliebter A, Babad J, Santamaria P, Serreze DV, Freeman GJ, Tarbell KV, Sharpe A, Dilorenzo TP. DEC-205-mediated antigen targeting to steady-state dendritic cells induces deletion of diabetogenic CD8+ T cells independently of PD-1 and PD-L1. Int Immunol, 25: 651-660, 2013.
• Ziegler AI, Le Page MA, Maxwell MJ, Stolp J, Guo H, Jayasimhan A, Hibbs ML, Santamaria P, Miller JF, Plebanski M, Silveira PA, Slattery RM. The CD19 signalling molecule is elevated in NOD mice and controls type 1 diabetes development. Diabetologia,  56:2659-2668, 2013.
• Clemente-Casares X, Santamaria P. Nanomedicine in autoimmunity. Immunol Lett, 158:167-174, 2014.
• Toselli C, Hyslop CM, Hughes M, Natale DR, Santamaria P, Huang C. Contribution of a Non-β-Cell Source to β-Cell Mass during Pregnancy. PLOS One 9(6):e100398, 2014.
• Wang J, Nanjundappa R, Shameli A, Clemente-Casares X, Yamanouchi J, Elliott J, Slattery R, Serra P, Santamaria P. The cross-priming capacity and direct presentation potential of an autoantigen are separable and inversely related properties. J Immunol, 193: 3296-3307, 2014.
• Garabatos N, Blanco J, Fandos C, Lopez E, Santamaria P, Ruiz A, Perez-Vidakovics ML, Benveniste P, Galkin O, Zuñiga-Pflucker JC, Serra P. A monoclonal antibody against the extracellular domain of mouse and human epithelial V-like antigen 1 reveals a restricted expression pattern among CD4- CD8- thymocytes. Monoclon Antib Immunodiagn Immunother, 33: 305-311, 2014.
• Babad J, Mukherjee G, Follenzi A, Ali R, Roep BO, Shultz LD, Santamaria P, Yang OO, Goldstein H, Greiner DL, DiLorenzo TP. Generation of β cell-specific Human Cytotoxic T Cells by Lentiviral Transduction and Their Survival in Immunodeficient HLA-transgenic Mice. Clin Exp Immunol. 2014 (in press)