Idoia Blanco Luquin

• PhD
• PostDoc Position at Navarrabiomed

Recent studies show that patients with Alzheimer’s disease (AD) harbor specific methylation marks in the brain that, if accessible, could be used as epigenetic biomarkers. Liquid biopsy enables the study of circulating cell-free DNA (cfDNA) fragments originated from dead cells, including neurons affected by neurodegenerative processes. Here, we iso...

Background : Recent studies show that Alzheimer’s disease (AD) patients harbor specific methylation marks in the brain. However, accessing this epigenetic information “locked in the brain” while patients are alive is challenging. Liquid biopsy technique enables the study of circulating cell-free DNA (cfDNA) fragments originated from cells that have...

In recent years, new DNA methylation variants have been reported in genes biologically relevant to Alzheimer’s disease (AD) in human brain tissue. However, this AD-specific epigenetic information remains brain-locked and unreachable during patients’ lifetimes. In a previous methylome performed in the hippocampus of 26 AD patients and 12 controls, w...

Background: Neuroinflammation, and specifically microglia, plays an important but not-yet well-understood role in the pathophysiology of amyotrophic lateral sclerosis (ALS), constituting a potential therapeutic target for the disease. Recent studies have described the involvement of different microglial transcriptional patterns throughout neurodege...

Background and Objective There is an urgent need to identify novel non-invasive biomarkers for Alzheimer's disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogene...

Background and objectives: there is growing evidence of the contribution of neuroinflammation, and in particular microglia, in the pathogenesis of amyotrophic lateral sclerosis (ALS). TREM2 gene plays a crucial role in shaping microglia in neurodegenerative conditions. To deepen the understanding of TREM2 in ALS and investigate the performance of...

Alzheimer’s disease (AD) is the most common cause of age-related dementia. Amyloid precursor protein (APP) is the precursor of Aβ peptides, and its role in AD has been widely investigated. Recently, it has been reported that a circular RNA (circRNA) originated from APP gene can serve as a template for Aβ synthesis, postulating it as an alternative...

Background: This work investigated the diagnostic accuracy of a blood-based DNA methylation marker panel as a non-invasive tool to identify Alzheimer's disease (AD) patients. Methods: Blood DNA methylation levels at 46 CpG sites (21 genes selected after a comprehensive literature search) were measured in 80 patients with probable AD dementia and 10...

Genetic variants in TREM2, a microglia-related gene, are well-known risk factors for Alzheimer’s disease (AD). Here, we report that TREM2 originates from circular RNAs (circRNAs), a novel class of non-coding RNAs characterized by a covalent and stable closed-loop structure. First, divergent primers were designed to amplify circRNAs by RT-PCR, which...

In view of the proven link between adult hippocampal neurogenesis (AHN) and learning and memory impairment, we generated a straightforward adult neurogenesis in vitro model to recapitulate DNA methylation marks in the context of Alzheimer’s disease (AD). Neural progenitor cells (NPCs) were differentiated for 29 days and Aβ peptide 1–42 was added. m...

The HOMER1 gene is involved in synaptic plasticity, learning and memory. Recent studies show that circular RNA derived from HOMER1 (circHOMER1) expression is altered in some Alzheimer’s disease (AD) brain regions. In addition, HOMER1 messenger (mRNA) levels have been associated with β-Amyloid (Aβ) deposits in brain cortical regions. Our aim was to...

Circular RNAs (circRNAs) are a novel class of noncoding RNAs characterized by a covalent and stable closed loop structure. circRNAs are enriched in neural tissues, particularly at synapses, where they are involved in synaptic plasticity. Alzheimer's disease (AD) is considered a synaptopathy since neurodegeneration causes loss or dysfunction of syna...

Adult neurogenesis was one of the most important discoveries of the last century, helping us to better understand brain function. Researchers recently discovered that microglia play an important role in this process. However, various questions remain concerning where, at what stage, and what types of microglia participate. In this review, we demons...

Background: The discovery of novel biomarkers of stroke etiology would be most helpful in management of acute ischemic stroke patients. Recently, circular RNAs (circRNAs) have been proposed as candidate biomarkers of neurological conditions due to its high stability. circRNAs function as sponges, sequestering miRNAs and are involved in most releva...

Background In the field of precision medicine, liquid biopsy has been developed as a non‐invasive blood test to isolate circulating cell‐free DNA (cfDNA). Although liquid biopsy has gained much attention in oncology as a diagnostic tool, the role of liquid biopsy to aid diagnosis in neurodegenerative diseases remains unclear. Here, we investigated...

Cancer cells acquire resistance to cytotoxic therapies targeting major survival pathways by adapting their metabolism. The AKT pathway is a major regulator of human pancreatic adenocarcinoma progression and a key pharmacological target. The mechanisms of adaptation to long-term silencing of AKT isoforms of human and mouse pancreatic adenocarcinoma...

The discovery of new biomarkers would be very valuable to improve the detection of early Alzheimer’s disease (AD). DNA methylation marks may serve as epigenetic biomarkers of early AD. Here we identified epigenetic marks that are present in the human hippocampus from the earliest stages of AD. A previous methylome dataset of the human AD hippocampu...

Mindfulness and meditation techniques have proven successful for the reduction of stress and improvement in general health. In addition, meditation is linked to longevity and longer telomere length, a proposed biomarker of human aging. Interestingly, DNA methylation changes have been described at specific subtelomeric regions in long-term meditator...

Background: The role of the microglia-related gene triggering receptor expressed in myeloid cells 2 (TREM2) in primary tauopathies, such as progressive supranuclear palsy (PSP), still remains unclear. Objectives: The objective of this study was to profile overall and transcript-specific TREM2 expression levels in the substantia nigra (SN) of PSP...

Background: Drawing the epigenome landscape of Alzheimer's disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays. Result...

Aim: To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells. Background: While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen b...

Lamins are fibrillary proteins that are crucial in maintaining nuclear shape and function. Recently, B-type lamin dysfunction has been linked to tauopathies. However, the role of A-type lamin in neurodegeneration is still obscure. Here, we examined A-type and B-type lamin expression levels by RT-qPCR in Alzheimer’s disease (AD) patients and control...

Background: Whole-exome sequencing has revealed a rare missense variant in PLD3 gene (rs145999145) to be associated with late onset Alzheimer's disease (AD). Nevertheless, the association remains controversial and little is known about the role of PLD3 in AD. Interestingly, PLD3 encodes a phospholipase that may be involved in amyloid precursor pro...

Introduction Cervical cancer (CC) is the fourth most common cancer among women worldwide, with around 50% of mortality. Therefore, new prognostic biomarkers are necessary to improve its poor outcome. Micro-RNAs (miRs) are small non-coding RNAs, mainly associated with gene expression silencing, and deregulated in cancer. Our aim was to identify miRs...

While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. Here we tested the potential synergi...

Noninvasive tests to diagnose and monitor the progression of neurodegenerative disorders have been a challenge for decades. The aim of this study was to explore the feasibility of applying liquid biopsy procedures to patients with a neurodegenerative disease such as amyotrophic lateral sclerosis (ALS). We isolated plasma cell‐free DNA (cfDNA) in 20...

Immunotherapy has radically transformed the management of metastatic malignant melanoma. Ipilimumab, a CTLA-4-targeted monoclonal antibody, was the first immunotherapeutic drug to reach a survival benefit compared with traditional chemotherapy. PD-1 targeted therapies, pembrolizumab and nivolumab, have demonstrated, in recent clinical trials, to be...

The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplas...

Background Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein involved in cell-cell adhesion and metastasis. Its role in cancer is controversial because it has been described as being upregulated in colorectal cancer, whereas it is downregulated in metastatic melanoma. However, its status in breast cancer (BC) is unknown. The purpose...

We analysed the promoter methylation status of five genes, involved in adhesion (EPB41L3, TSLC-1), apoptosis (RASSF1, RASSF2) or angiogenesis (TSP-1), in intraoperative sentinel lymph node (SLN) biopsy samples from patients with breast cancer, that had been processed by the one-step nucleic acid amplification (OSNA) technique. SLN resection is perf...

Immunotherapies are achieving clinical success for the treatment of many cancers. However, it has taken a long time to exploit the potential of the immune system for the treatment of human cancers. We cannot forget that this has been the consequence of very extensive work in basic research in preclinical models and in human patients. Thus, it is ra...

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that are defined by their myeloid origin, immature state and ability to potently suppress T cell responses. They regulate immune responses and the population significantly increases in the tumor microenvironment of patients with glioma and other malignant tumors. For t...

Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are...

Since the beginning of the 20th century, biomedical scientists have tried to take advantage of the natural anti-cancer activities of the immune system. However, all the scientific and medical efforts dedicated to this have not resulted in the expected success. In fact, classical antineoplastic treatments such as surgery, radio and chemotherapy are...

Cervical cancer is the third most common cancer in women worldwide. The hypermethylation of P16, TSLC-1 and TSP-1 genes was analyzed in squamous cell carcinomas (SCC), cervical intraepithelial lesions (CIN) and adenocarcinomas (ADC) of the uterine cervix (total 181 lesions). Additionally human papillomavirus (HPV) type, EPB41L3, RASSF1 and RASSF2 h...

Myeloid-derived suppressor cells (MDSCs) differentiate from bone marrow precursors, expand in cancer-bearing hosts and accelerate tumor progression. MDSCs have become attractive therapeutic targets, as their elimination strongly enhances anti-neoplastic treatments. Here, immature myeloid dendritic cells (DCs), MDSCs modeling tumor-infiltrating subs...

Breast cancer is a heterogeneous disease that can be subdivided into clinical, histopathological and molecular subtypes (luminal Alike , luminal B-like/HER2-negative, luminal B-like/HER2-positive, HER2-positive, and triple-negative). The study of new molecular factors is essential to obtain further insights into the mechanisms involved in the tumor...

Hypermethylation of tumor suppressor genes is one of the hallmarks in the progression of brain tumors. Our objectives were to analyze the presence of the hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, and to establish their association with the pat...

Myeloid-derived suppressor cells (MDSCs) exhibit potent immunosuppressive activities in cancer. MDSCs infiltrate tumors and strongly inhibit cancer-specific cytotoxic T cells. Their mechanism of differentiation and identification of MDSC-specific therapeutic targets are major areas of interest. We have devised a highly efficient and rapid method to...

Efficacious anti-tumour vaccines need to strongly stimulate cancer-specific effector T cells and counteract the activity of tumour-infiltrating immunosuppressive cells. We hypothesised that combining cytokine expression with PD-L1 silencing could potentiate anti-cancer immune responses of lentivector vaccines. Thus, we engineered a collection of le...

Since dendritic cells operate as professional antigen-presenting cells (APCs) and hence are capable of jumpstarting the immune system, they have been exploited to develop a variety of immunotherapeutic regimens against cancer. In the few past years, myeloid-derived suppressor cells (MDSCs) have been shown to mediate robust immunosuppressive functio...

Since dendritic cells operate as professional antigen-presenting cells (APCs) and hence are capable of jumpstarting the immune system, they have been exploited to develop a variety of immunotherapeutic regimens against cancer. In the few past years, myeloid-derived suppressor cells (MDSCs) have been shown to mediate robust immunosuppressive functio...

Since the first human gene therapy clinical trials were proven successful in 2000, human gene therapy has witnessed setbacks as well as encouraging progress. While these first clinical trials were performed with a γ-retrovirus vector to correct X-linked severe combined immunodeficiency (SCID-X1) in children, others since then have applied similar o...

Our work over the past eight years has focused on the use of HIV-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (DCs) to control their functions in immune modulation. DCs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including T, B and NK cells. Their ge...

To determine the effect of retinoic acid (RA) in neuroblastoma we treated RA sensitive neuroblastoma cell lines with 9-cis RA or ATRA for 9 days, or for 5 days followed by absence of RA for another 4 days. Both isomers induced apoptosis and reduced cell density as a result of cell differentiation and/or apoptosis. Flow cytometry revealed that 9-cis...

Neuroblastoma is a malignant embryonal childhood tumor of the peripheral nervous system, which often shows poor clinical prognosis. p53 mutations are rare at diagnosis of neuroblastoma but may be acquired at relapse, as well as chemoresistance. We have previously detected a mutation in exon 5 of the p53 gene (codon 135; Cys to Phe) in the SK-N-FI n...