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Title: Gene regulatory mechanisms underlying the emergence of novel neuronal functions

Autor: Andrea Millán Trejo

Unidad de Neurobiología del Desarrollo. IBV, CSIC

Speaker: Álvaro Rada Iglesias

«Synthetic engineering of enhancer landscapes provides novel insights into long-range gene regulation».
Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC). Universidad de Cantabria/CSIC

V Jornadas sobre Gestión de la Oncología de Precisión de la Comunidad Valenciana Estrategia del cáncer en la Comunidad Valencia en 2025

12:00 – 12:30 – Vicente Felipo
Mechanisms leading to cognitive and motor impairment in hyperammonemia and hepatic encephalopathy. Therapeutic implications.

Abstract: The main objectives of our group are to identify the mechanisms by which liver diseases lead to cognitive and motor impairment in patients with minimal hepatic encephalopathy (MHE) and design and assess in rat models new treatments for MHE.
We have been working on these objectives for many years. In this seminar, I will summarize some of our key studies in the last years both in cirrhotic patients with MHE and in rat models of hyperammonemia and MHE.
Some questions that we are studying are:
Which peripheral alterations are responsible for induction of MHE in cirrhotic patients?
How these peripheral alterations are transmitted to the brain?
How this induces neuroinflammation?
How neuroinflammation impairs neurotransmission?
How impaired neurotransmission leads to cognitive and motor impairment?
We have shown that: a) MHE appearance in patients is due to a pro-inflammatory shift in peripheral inflammation; b) hyperammonemia induces inflammation and neuroinflammation, which lead to cognitive and motor impairment. c) peripheral inflammation induces neuroinflammation, increasing inflammatory factors in cerebellum and hippocampus that alter glutamate and GABA neurotransmission, membrane expression of glutamate and GABA receptors and transporters and extracellular levels of these neurotransmitters. This leads to cognitive and motor impairment. d) plasma extracellular vesicles (EV) from hyperammonemic rats, injected to control rats, induce neuroinflammation and cognitive and motor impairment, supporting that EV play a key role in the transmission of peripheral alterations to the brain and in cognitive and motor impairment.
We have been able to reverse cognitive and motor impairment in rats with hyperammonemia and MHE with different treatments acting on targets identified in the mechanistic studies.

12:30 – 13:00 – Amina Benaicha
TITLE

Abstract: 

Speaker: Patricia Centeno
CRUK Scotland Institute
Postdoctoral Fellow–R18 

Decoding Tumour Permissiveness in the Skin: From Keratinocytes to Melanocytes

Abstract: The skin undergoes continuous renewal, relying on stem and progenitor cells to maintain its barrier function. Over time, multiple oncogenic mutations accumulate, yet the skin often tolerates them without progressing to malignancy. The mechanisms underlying this selective tolerance across different cellular populations remain poorly understood.

In this talk, I will explore how MAPK pathway activation rewires the transcriptional network to generate permissive or non-permissive microenvironments for tumour initiation. First, I will talk about cutaneous squamous cell carcinoma (cSCC), a cancer derived from the keratinocytes. Using genetically engineered mouse models, we investigated the aetiology of rapidly developing cSCC observed in melanoma patients treated with BRAF inhibitors.

Our studies reveal distinct tumour-primed and tumourresistant keratinocyte populations and identify the pioneer  ranscription factor SOX2 as a key regulator of this differential response.

In the second part, I will shift focus to melanoma, arising from melanocytes, which co-inhabit the epidermis with keratinocytes. I will present unpublished data regarding melanocyte-keratinocyte crosstalk during  melanoma onset.

Preliminary data suggest that neurotrophic signalling and axon guidance pathways contribute to a neuron-like mode of communication that facilitates melanoma initiation. These results open new avenues of research at the interface of neuro and cancer sciences.

Title: Development of relevant preclinical models and polypeptide-based combination therapies for advanced prostate cancer

Autor: Antoni Serrano Marti

Abstract: Prostate cancer (PCa) often progresses from localized disease to castration-resistant form (CRPC) within five years in 20% of cases due to the reactivation of androgen receptor (AR) expression. CRPC development includes transitions from prostatic intraepithelial neoplasia to metastatic CRPC (mCRPC), with 65-75% of mCRPC cases leading to bone metastases, which complicates prognosis and treatment. Early-stage PCa treatment primarily employs prostatectomy and radiotherapy (RT); however, advanced forms lack effective treatments, with CRPC remaining highly lethal. Poly(ADP-ribose) polymerase inhibitors (PARPi) represent a promising targeted therapy for CRPC, particularly for patients with homologous recombination repair (HRR) deficiencies (e.g., BRCA1/BRCA2 mutations); however, clinical challenges (e.g., resistance mechanisms and side effects) hinder their efficacy. Combination therapies involving traditional treatment approaches (RT, abiraterone acetate (Abi), or docetaxel (Dtx)) combined with PARPi offer improved outcomes by driving synthetic lethality in HR-deficient cells. Despite their potential, combination therapy-based approaches face issues such as toxicity, antagonistic interactions and resistances. Nanomedicine offers solutions to some of these challenges, providing controlled drug delivery through passive and active targeting, improving bioavailability, and reducing side effects.

This research focuses on developing and characterizing a bone metastatic PCa model and evaluating the effects of nanomedicine-based therapies; furthermore, we evaluated the effects of PARPi-based combination therapies in vitro in 2D and 3D models and ultimately in vivo to optimize therapeutic outcomes in advanced PCa.

We established and characterized a bone metastatic PCa model, successfully applying this model to develop and evaluate nanomedicine-based therapeutics and combination therapies. We established and characterized novel 3D PCa models, from more straightforward (homospheroids) to more complex (heterospheroids), with the latter better mimicking tumor-stroma interactions. The 3D in vitro models and in vivo platforms effectively recapitulated TME complexity and PCa heterogeneity, providing valuable insights into therapeutic responses and resistance mechanisms. We synthesized and evaluated nanomedicinal forms of traditional therapeutics, demonstrating their potential to enhance drug delivery, reduce toxicity, and improve treatment efficacy. Furthermore, we investigated PARPi-based combination therapy with RT and Abi, highlighting synergistic effects.

Our integrated approach of molecular, preclinical, and therapeutic innovations offers promising approaches for optimizing advanced PCa treatment. We hope the routine use of these advanced models, which mirror the TME and PCa heterogeneity, will improve the development pipeline for nanomedicines and combination therapies, accelerating their clinical translation and enhancing patient outcomes.

Title: Obtaining and characterising consensus transcriptional profiles for understanding the progression and severity of spinal cord injury.

Autor: Rubén Grillo Risco
Directors: Victoria Moreno Manzano, Marta R Hidalgo García, Francisco García García

Abstract: Spinal cord injury (SCI) is a devastating condition that leads to motor, sensory, and autonomic dysfunction. Current therapeutic options remain limited,
emphasizing the need for a comprehensive understanding of the underlying SCI-associated molecular mechanisms. This study characterized distinct SCI
phases and severities at the gene and functional levels, focusing on biomarker gene identification. Our approach involved a systematic review, individual
transcriptomic analysis, gene meta-analysis, and functional characterization. We compiled a total of fourteen studies with 273 samples, leading to the
identification of severity- and phase-specific biomarker genes that allow the precise classification of transcriptomic profiles. We investigated the potential
transferability of severity-specific biomarkers and identified a twelve-gene signature that predicted injury prognosis from human blood samples. We
also report the development of MetaSCI-app – an interactive web application designed for researchers – that allows the exploration and visualization of all
generated results (https://metasci-cbl.shinyapps.io/metaSCI). Overall, we present a transcriptomic reference and provide a comprehensive framework for assessing
SCI considering severity and time perspectives, all integrated into a user-friendly tool.

12:00 – 12:30 – Anna Labernadie
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12:30 – 13:00 – Salvador Meseguer
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