Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3
Events by this organizer
march
03mar12:3013:30FBR: Marta Cascante
Event Details
Speaker: Marta Cascante Institution: Dept of Biochemistry and Molecular Biomedicine-Institute of Biomedicine (IBUB) University of Barcelona , Spain Place: Jerónimo Forteza CIPF conference room Abstract: Metabolic phenotyping from
Event Details
Speaker: Marta Cascante
Institution: Dept of Biochemistry and Molecular Biomedicine-Institute of Biomedicine (IBUB) University of Barcelona , Spain
Place: Jerónimo Forteza CIPF conference room
Abstract:
Metabolic phenotyping from cells to tumor biopsies: towards the design of personalized therapies
Colorectal cancer (CRC) is the second leading cancer in mortality, with the vast majority of its deaths attributable to distant metastasis. Even though genetic alterations drive cancer initiation, few genetic changes are identified during the metastatic process and epigenetic or metabolic changes have emerged as hallmarks of metastasis. Current standard-of-care for metastatic colorectal cancer (mCRC) patients includes chemotherapy such as FOLFOX and anti-angiogenic or anti-EGFR in microsatellite stable (MSS). Immunotherapy only has been successful for microsatellite instable (MSI) tumors. The efficacy of chemotherapy in CRC is limited by the emergence of chemoresistance, which remarks the need of new tools for patient selection for specific therapies and for the design of new combined therapies to overcome chemoresistance. Since metabolic reprogramming is known to be an important hallmark of cancer, tumor metabolic metabolism is considered a sensitive target in the design of combined therapies.
Here I will present our recent results characterizing metabolic adaptations of mCRC and on tools towards a metabolic classification of tumours that contribute to the identification of patient subsets more suitable for optimally tailored combined therapies.
First, I will show the workflow that we developed to integrate multiple layers of -omics data and characterize putative drug targets to impair metabolic adaptations that sustain CRC metastatic potential. Using this workflow, we built genome-scale metabolic flux models (GSMMs)Marta that allowed us to predicted and validated cystine uptake and folate metabolism as potential targets against mCRC.
Second, I will present our work in progress towards the identification of immunometabolic distinctive phenotypes conserved across diverse tumour types and the potential that offers the metabolic stratification of tumours in the design of patient-tailored combined therapies.
Finally, I will discuss the possibilities that offer GSMMs to complement integrated physiology towards the identification of metabolic key players in metabolic diseases and to inform the design of new combined therapies.
Time
(Friday) 12:30 - 13:30
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
10mar12:0013:00SEMINAR: Camilla Pegoraro / Francesca de Angelis
Event Details
12:00 – 12:30 Camilla Pegoraro Novel polypeptide-based drug delivery systems for precise mitochondria targeting In today’s pharmaceutical era, many emerging therapies rely on releasing therapeutics at a subcellular
Event Details
12:00 – 12:30 Camilla Pegoraro
Novel polypeptide-based drug delivery systems for precise mitochondria targeting
In today’s pharmaceutical era, many emerging therapies rely on releasing therapeutics at a subcellular level. Given the role of mitochondrial dysfunctions in diseases such as cancer, there is a particular focus on developing systems targeting mitochondria specifically. However, it is challenging to deliver therapies to this organelle due to its compartmentalized and difficult-to-penetrate membranes, as well as the need to bypass the cell membrane and ensure cytosolic delivery. Polypeptide-based systems offer a promising solution for delivering therapeutics in a controlled and targeted manner.
In this context, within my Ph.D. thesis being performed as part of the Marie Curie International Training Network (ITN) Biomolmacs, we have designed, synthesized and characterized two different polyornithine (PLO)-based systems with a high propensity for mitochondria. In the first platform, a complex system based on PLO and TPP was designed to ensure cytosolic release after endocytosis and mitochondria targeting. In the second design, PLO-based diblock copolymers were developed to target the mitochondria after direct cell membrane permeation. Internalization studies by confocal fluorescence microscopy and extensive studies with model membrane systems (GUVs and SUVs) were applied to confirm the mitochondria affinity. To test the effectiveness of the diblock copolymer carrier, we covalently linked two drugs that target mitochondria, lonidamine and α-tocopherol succinate (TOS), and evaluated their activity by analyzing the mitochondria membrane potential with the JC-1 assay and measuring the mitochondria respiration using Seahorse Analytics. Moreover, the mitochondria targeting vector was covalently coupled to a molecular motor to test the hybrid system’s effectiveness in enhancing membrane permeation. In conclusion, we designed, characterized and extensively tested in vitro novel mitochondria-targeted platforms and their derivatives with promising features as a subcellular cancer therapy.
12:30 – 13:00 Francesca de Angelis
HAPLN1 is a driver for peritoneal carcinomatosis in PDAC
Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Despite the cancer cell intrinsic features, a key regulator of metastasis is the microenvironment that tumor cells are facing during their metastatic journey. Here, we show that a protein of the extracellular matrix, HAPLN1, which crosslinks Hyaluronan (HA) and proteoglycan, is associated with worse overall patient survival. Its presence in the extracellular matrix enhances tumor cell plasticity and PDAC metastasis in the peritoneal cavity. Mechanistically, we observed that HAPLN1 promotes upregulation of Hyaluronan (HA) production, facilitating EMT, stemness, invasion and immunomodulation. As such, we identified HAPLN1 as a prognostic marker and as a driver for peritoneal metastasis in PDAC.
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
Event Details
«The new reality of the Mediterranean: accelerating impacts of climate change” Speaker: Samira Khodayar Pardo Institution: Head of the Meteorology and Climatology Department of the Mediterranean Center for Environmental Studies (CEAM),
Event Details
«The new reality of the Mediterranean: accelerating impacts of climate change”
Speaker: Samira Khodayar Pardo
Institution: Head of the Meteorology and Climatology Department of the Mediterranean Center for Environmental Studies (CEAM), Valencia, Spain, and Distinguished Researcher of Excellence (CIDEGENT-GVA)
Place: CIPF conference room
The Mediterranean basin is a hot spot for climate change warming up to 1.5 times faster than the rest of the world with the Mediterranean Sea warming three times more than the oceans (MedECC 2020). A consensus exists about the magnification of extreme phenomena in the area under climate change (IPCC 2021). In fact, several types of risks currently affect and will continue affecting the region severely, from more frequent extreme weather events such as heat waves, droughts, or floods, to increasing sea surface temperature and coastal erosion due to rising sea levels. The impacts affect the region’s ecosystems, economic activities, and, ultimately, human health. In addition, the effects also spread like “cascades” that generate multiple impacts in all socioeconomic sectors. Current change and future scenarios consistently point to significant and increasing risks during the coming decades in most impact domains such as water and energy resources, ecosystems, agriculture and food, fishery, health, and human security.
The impacts of climate change have accelerated on the Mediterranean coast of the Iberian Peninsula in the last decades. In this presentation, we will discuss this acceleration based on observations of the notorious and progressive rise in atmospheric and sea surface temperature and the generalized reduction of mean accumulated precipitation in the region. In this context, the magnification of extreme weather phenomena in the region will be described in detail focusing on the spatio-temporal evolution of terrestrial and marine heat waves, as well as extreme precipitation in the autumn period.
Time
(Friday) 12:30 - 13:30
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
april
Event Details
Thesis Title: Funciones del factor de inicio de la traducción eucariota 5A2 en el cáncer de pulmón Author: Arantxa Martínez Férriz PhD. Supervisors: Rosa Farràs Rivera, Dr. Ramón Serrano Salom Summary:
Event Details
Thesis Title: Funciones del factor de inicio de la traducción eucariota 5A2 en el cáncer de pulmón
Author: Arantxa Martínez Férriz
PhD. Supervisors: Rosa Farràs Rivera, Dr. Ramón Serrano Salom
Summary:
El factor de iniciación eucariota 5A (eIF-5A), un factor de traducción esencial, es activado postraduccionalmente por la poliamina espermidina. Dos genes humanos codifican eIF-5A, eIF5- A1 cuya expresión es constitutiva, y eIF5-A2 que se encuentra frecuentemente sobreexpresado en tumores humanos. incluyendo el cáncer de pulmón no microcítico (CPNM). Recientemente se ha correlacionado la sobreexpresión de eIF5A2 con la transición epitelio-mesenquimal (EMT) y la metástasis. eIF-5A2 se considera una diana terapéutica muy atractiva en el cáncer dado que su expresión se asocia con cáncer, y los ratones knock-out para eIF-5A2 son viables y tienen un desarrollo normal. Sin embargo, la regulación de eIF-5A2, su activación y su papel funcional como factor de traducción en células cancerosas aún no se conoce bien. El presente trabajo de tesis doctoral tiene como objetivo caracterizar el papel patológico de eIF5A2 en el desarrollo del CPNM. Para ello, hemos estudiado el papel de eIF5A2 en la proliferación, motilidad e invasión celular. Así mismo, se ha estudiado el efecto de su inhibición farmacológica en líneas celulares de CPNM. Los resultados obtenidos sugieren la existencia de una regulación entre las isoformas eIF5A1 y eIF5A2 para compensar la expresión de ambos homólogos. Además, nuestros datos apuntan a una coordinación temporal y posicional entre las vías TGFβ1 y eIF5A2 para impulsar la traducción de proteínas necesarias para la organización del citoesqueleto y la adquisición de características de motilidad propias de células invasivas. Por tanto, eIF5A2 podría ser empleado como un biomarcador de mal pronóstico en CPNM y su inhibición farmacológica podría emplearse como una posible herramienta terapéutica en aquellos casos en los que eIF5A2 se encuentre sobreexpresado.
Time
(Wednesday) 11:00 - 14:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
21apr12:0013:00SEMINAR: Paula Doria / Javier González Fernández
Event Details
12:00 – 12:30 Paula Doria 12:30 – 13:00 Javier González Fernández
Event Details
12:00 – 12:30 Paula Doria
12:30 – 13:00 Javier González Fernández
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
28apr12:3013:30FBR: Amanda Sferruzzi-Perri
Event Details
Speaker: Amanda Sferruzzi-Perri Institution: Physiology, Development and Neuroscience Department, Centre for Trophoblast Research, University of Cambridge. United Kingdom. Place: CIPF conference room Abstract:
Event Details
Speaker: Amanda Sferruzzi-Perri
Institution: Physiology, Development and Neuroscience Department, Centre for Trophoblast Research, University of Cambridge. United Kingdom.
Place: CIPF conference room
Abstract:
Time
(Friday) 12:30 - 13:30
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
may
Event Details
Speaker: Prof. Jochen Prehn Institution: Centre for Systems Medicine Dublin, Ireland Place: Salón de Actos Jerónimo Forteza CIPF TITLE: Bugs, Fungi and Cells in Cells – the weird side of colorectal
Event Details
Speaker: Prof. Jochen Prehn
Institution: Centre for Systems Medicine Dublin, Ireland
Place: Salón de Actos Jerónimo Forteza CIPF
TITLE: Bugs, Fungi and Cells in Cells – the weird side of colorectal cancer and tumour progression
Abstract: My talk will focus on two new aspects of cancer biology and tumour progression in the setting of colorectal cancer: the role of the microbiome and the role of cell dynamics and formation of cell-in-cell structures.
Entosis is a form of non-phagocytic cell-in-cell (CIC) interaction where a living cell enters into another. Tumours show evidence of entosis, however factors controlling entosis remain to be elucidated. I will present data showing that death receptor activation is a potent induces of entosis in colon cancer cells. Induction of entosis and apoptosis by an activation of death receptors by ligands such as TRAIL occurred simultaneously and required the presence of caspase-8. Analysis of colorectal cancer tumours showed a significant association between expression levels of TRAIL and CICs. Notably, the presence of CICs in the invasive front regions of colorectal tumors was significantly correlated with adverse patient prognosis.
Dysbiosis of the microbiome has also been implicated in colorectal cancer (CRC) development, progression and response to therapy. Fusobacterium nucleatum (Fn), a commensal Gram-negative anaerobe from the Fusobacteriales order, is an onco-bacterium in CRC as a causal relationship between Fn prevalence and CRC pathogenesis, progression and treatment response has been reported in vivo. We showed that Fn/Fusobacteriales prevalence is associated with immune involvement (decrease in macrophages M1 and increase in macrophages M2) and activation of specific signalling programs (inflammation, DNA damage, WNT, metastasis, proliferation, cell cycle) in the host tumours, and is prognostic in particular in mesenchymal CRC tumors. We also systematically investigated alterations in the bacteriome and mycobiome of CRC patients in tumours and matched adjacent mucosa resulting in the identification of microbiome-based subtypes associated with host clinico-pathological and molecular characteristics. Tumours and adjacent mucosa samples were classified into 4 microbial subtypes, termed C1 to C4, based on the bacteriome and mycobiome composition. Microbial subtypes were associated with distinct tumour and patient phenotypes including T stage, tumour location, history of colon polyps and other malignancies, age, lymphovascular invasion and p53 status and disease-free survival.
Time
(Friday) 12:30 - 13:30
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
19may12:0013:00SEMINAR: Gergana Mincheva / Irene Soler
Event Details
12:00 – 12:30 Gergana Mincheva 12:30 – 13:00 Irene Soler
Event Details
12:00 – 12:30 Gergana Mincheva
12:30 – 13:00 Irene Soler
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
26may12:0013:00SEMINAR: Milagros Buffa / María Ibáñez
Event Details
12:00 – 12:30 Milagros Buffa 12:30 – 13:00 María Ibáñez
Event Details
12:00 – 12:30 Milagros Buffa
12:30 – 13:00 María Ibáñez
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
june
09jun12:0013:00SEMINAR: María Ángeles Juanes / Marcos Agustina Hernández
Event Details
12:00 – 12:30 María Ángeles Juanes 12:30 – 13:00 Marcos Agustina Hernández
Event Details
12:00 – 12:30 María Ángeles Juanes
12:30 – 13:00 Marcos Agustina Hernández
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
30jun12:0013:00SEMINAR: Paula Hernández Calderón / Luke Noon
Event Details
12:00 – 12:30 Paula Hernández Calderón 12:30 – 13:00 Luke Noon
Event Details
12:00 – 12:30 Paula Hernández Calderón
12:30 – 13:00 Luke Noon
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain