The main focus of Dr. Santamaria’s scientific career has been to try to understand the immunogenetics and immunopathogenesis of autoimmune disorders, with a particular focus on type 1 diabetes, to try to find targets for therapeutic intervention.
Early efforts focused on the relationship between genetic susceptibility and resistance to autoimmunity and T-cell tolerance. This work culminated in the discovery of a new therapeutic platform for the treatment of chronic inflammatory disorders based on nanomedicine. This therapeutic approach triggers the formation of extensive antigen- and disease-specific networks of regulatory T and β-cells that efficiently suppress the progression of several different autoimmune disorders without compromising systemic immunity.
Current efforts focus on dissecting the mechanisms that sustain and regulate these regulatory cellular networks, the developmental origin(s) of their cellular components and the molecules that control cell-to-cell communication within the networks. Mice humanized with peripheral blood mononuclear cells from patients are used to select candidate nanomedicines for clinical development. Ultimately, Santamaria’s goal is to bring this new technology to the clinic.
Industry Expertise (3)
Areas of Expertise (4)
University of Barcelona: MD, Medicine 1983
University of Barcelona: PhD, Medicine 1987
- Group Leader : Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS) Barcelona Spain
- Founder : Parvis Therapeutics
Media Appearances (1)
Calgary researchers working on new way to treat autoimmune diseases
CBC Calgary online
Dr. Pere Santamaria said they've found a class of drugs that selectively targets cells that cause autoimmune diseases like Type I diabetes and multiple scleroisis without impairing a patient's immune system.
Regulatory T cells hold promise as targets for therapeutic intervention in autoimmunity, but approaches capable of expanding antigen-specific regulatory T cells in vivo are currently not available. Here we show that systemic delivery of nanoparticles coated with autoimmune-disease-relevant peptides bound to major histocompatibility complex class II (pMHCII) molecules triggers the generation and expansion of antigen-specific regulatory CD4+ T cell type 1 (TR1)-like cells in different mouse models, including mice humanized with lymphocytes from patients, leading to resolution of established autoimmune phenomena.
Blunting autoreactivity without compromising immunity remains an elusive goal in the treatment of autoimmunity. We show that progression to autoimmune diabetes results in the conversion of naive low-avidity autoreactive CD8+ T cells into memory-like autoregulatory cells that can be expanded in vivo with nanoparticles coated with disease-relevant peptide-major histocompatibility complexes (pMHC-NP).
Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2).
Antigen therapy may hold great promise for the prevention of autoimmunity; however, most clinical trials have failed, suggesting that the principles guiding the choice of treatment remain ill defined. Here, we examine the antidiabetogenic properties of altered peptide ligands of CD8+ T cells recognizing an epitope of islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP206–214), a prevalent population of autoreactive T cells in autoimmune diabetes.
For unknown reasons, autoimmune diseases such as type 1 diabetes develop after prolonged periods of inflammation of mononuclear cells in target tissues1. Here we show that progression of pancreatic islet inflammation to overt diabetes in nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7)2 in the context of H-2K d class I molecules of the major histocompatibility complex (MHC).