RETOS-COLABORACION Project (2014-2017)
National Plan of Scientific and Technological Research, and Innovation (2013-2016)
Project supported by the Ministry of Economy and Competitiveness, National Plan for Scientific and technological Research, and Innovation, 2014-2016, addressing the Society Challenges in the National Plan for Scientific and technological Research, and Innovation frame (RTC-2014-2415-1) and by the European Union through the Regional Development European Fund (FEDER).
Project Title
GPBP activity profiling in plasma to ensure the clinical development of GPBP inhibitor drug candidates [RTC-2014-2415-1]
Project Abstract
GPBP [Goodpasture antigen-binding protein] is a protein with at least three main activities through a cycle, namely: protein kinase (cytoplasm and eventually core), chaperone (endoplasmic reticulum) and cytokine inflammatory (extracellular compartment). Our recent results have shown that GPBP hyperactivity cycle underlies in the pathogenesis of many disorders including: autoimmunity and inflammation (Goodpasture's disease, immune complex glomerulonephritis and rheumatoid arthritis), cancer and more recently in diabetes type 2. Previous granted projects (IPT and IPT-2010-045-2011-1527) have obtained a prototype to detect GPBP in plasma for diagnosis in patients with rheumatoid arthritis, and GPBP inhibitors of both its intracellular kinase activity (SME-T12) and blocking their extracellular activity of GPBP (mAb-N26) that have proven effective in preclinical studies to treat lung cancer and renal lupus, respectively.
To develop the clinical phases of GPBP inhibitors, robust biomarkers are required to detect patients with disorders GPBP dependent, so it intends to carry out pre-clinical and clinical studies aimed to define a proteomic and metabolomic fingerprint in plasma.
The main objectives are: 1) Plasma Profiling in animal models with GPBP cycle hyperactivity. 2) Plasma profiling in patients with GPBP cycle hyperactivity disorders dependent. 3) Crystallization of GPBP-T12 complex. 4) Complete the pre-regulatory pre-clinical stages of T12 for lung cancer and N26 for renal lupus.
INNPACTO Project (2011-2014)
National Plan of Scientific Research, Development and Technological Innovation (2008-2011)
Project supported by the Ministry of Economy and Competitiveness, National Plan for Scientific Research, Development and Technological Innovation, 2008-2011, sub-program INNPACTO 2011 (IPT-2011-1527-010000) and by the European Union through the Regional Development European Fund (FEDER).
Project Title
Development of a diagnostic test and drug candidates based on GPBP Technology [IPT-2011-1527-010000]
Project Abstract
GPBP [Goodpasture antigen-binding protein] regulates the assembly of quaternary structures complex, a previously unrecognized biological role that has implications for normal development and performance of different tissues and organs. GPBP are involved in several pathogenies: glomerulonephritis from autoimmune disorders (Goodpasture's disease, IgA nephropathy, renal lupus), rheumatoid arthritis and chemoresistance in cancer, previously non-related disorders which have a unknown origin without a specific treatment.
The main project objectives are : 1) Validation of a GPBP detection prototype for clinical use in autoimmunity (Goodpasture disease , IgA nephropathy , renal lupus and rheumatoid arthritis) and cancer; 2) Development of drug candidates from Q2 peptidomimetic for treating chemoresistant cancer and monoclonal antibodies for treatment of autoimmune diseases (Goodpasture's disease, IgA nephropathy, renal lupus and rheumatoid arthritis).
Prometheus Project (2009-2013)
Prometheus Program
Prometheus Program aims to identify, support and empower R&D groups of excellence of the Comunitat Valenciana. Project supported by the Conselleria d’ Educació, formació i ocupació de la Generalitat Valenciana.
Project Title
The role of GPBP in glomerular basement membrane collagen organization and in the pathogenesis of immune glomerulonephritis.
Project Abstract
GPBP [Goodpasture antigen-binding protein] is a nonconventional Ser / Thr kinase that phosphorylates the noncollagenous-1 (NC1) domain of the α3 chain of type IV collagen [α3 (IV) NC1]. The α3(IV)NC1 domain diversifies its structure and multiple conformations (conformers) of this domain assemble into the collagen network of basement membranes.
The evidence indicates that GPBP is a constituent of the cellular machinery that catalyzes structural diversification and assembly of the α3(IV)NC1 domain in the glomerular basement membrane (GBM).
Recent studies indicate that an increase in glomerular expression of GPBP is associated with the formation and assembly of aberrant conformers, GBM dissociation and autoantibody production, suggesting that the Goodpasture's autoimmune response is a legitimate reaction of the immune system against the aberrant conformations of the domain α3(IV)NC1 that disrupt GBM collagen network.
The main objectives of our research include: 1) Determine the mechanism of action of GPBP in structural diversification and assembly of the α3(IV)NC1 domain, 2) Characterize the structural changes that activate the immune system in Goodpasture's disease and immunecomplex deposit formation in IgA nephropathy, 3) Strengthen our pathogenic model and propose GPBP as biomarker and therapeutic target in immune glomerulonephritis.
Prometheus Project Phase II (2014-2017)
Prometheus Program
Prometeo Program Phase II to support international projection and knowledge transfer of the R&D excellence groups of the Comunitat Valenciana who joined the Prometheus Program in 2009 and 2010. Project supported by the Conselleria d’ Educació, Cultura i Esports de la Generalitat Valenciana.
TÃtulo del Proyecto
GPBP (Goodpasture antigen-binding protein) activity profiling in plasma and GPBP-T12 complex structure resolution to ensure the clinical development of T12, the first GPBP inhibitor drug candidate.[PROMETEOII/2014/048]
TRACE Project (2010-2013)
TRACE Subprogram (2008-2011)
Scientific Research focus on knowledge transfer to companies (TRACE). Project supported by the Ministry of Science and Innovation, National Plan for Scientific Research, Development and Technological Innovation, 2008-2011.
Project Title
Determination of GPBP the serum levels in patients with nephritis. [TRA2009-0026]
Project Abstract
The cells produce two isoforms of GPBP of 77- and 91-kDa generated by alternative initiation of the mRNA translation. 91-kDa GPBP binds to cell membranes and regulates the secretion of the 77-kDa isoform to the extracellular compartment. GPBP plasma levels of 77-kDa (circulating GPBP) are upregulated in Goodpasture patients and IgA nephropathy in mice models, suggesting that GPBP is a biomarker for antibody-mediated glomerulonephritis. The project aims at developing strategies for monitoring these glomerulonephritis based on the determination of GPBP levels in plasma (serum) using a prototype of detection and the assessment of its clinical utility in nephrology patients that would define GPBP as a new biomarker for early detection and monitoring of this disease. For this, two complementary approaches will be made: 1) measuring levels of GPBP in nearly one hundred thousand samples of a serum bank of nephrology patients; and 2) monitoring the levels of GPBP in nephrology patients from Hospitals of reference.
