Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3
Events by this organizer
may
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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
Event Details
Myelin regeneration: from gene therapy to energy metabolism Speaker: Dr. Vanja Tepavcevic Institution: Departamento de Neurociencias, Facultad de Medicina y Enfermería, Universidad del País Vasco. Leioa, Spain Place: CIPF conference room
Event Details
Myelin regeneration: from gene therapy to energy metabolism
Speaker: Dr. Vanja Tepavcevic
Institution: Departamento de Neurociencias, Facultad de Medicina y Enfermería, Universidad del País Vasco. Leioa, Spain
Place: CIPF conference room
Abstract: Multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS), is the leading cause of acquired neurological disability in young adults. Current treatments are immunomodulatory and provide temporary relief during relapses, but mostly lack an effect on disability progression, caused by axonal degeneration. Remyelination (myelin repair) of demyelinated axons reduces axonal degeneration in mice and patients, but this process eventually fails with disease progression. Thus, promoting remyelination in MS is a potential therapeutic strategy to prevent irreversible neurological deficits. So far, the search for pro-remyelinating agents has focused primarily on compounds that promote differentiation of oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the CNS, thus generation of new oligodendrocytes. Yet, clinical trials performed have shown modest functional benefits and scarce impact on the clinical outcome. In this talk, I will we argue that achieving clinical benefits in patients with MS will likely require complementary/alternative approaches to stimulate remyelination. I will present our recently published data on gene therapy as a therapeutically relevant strategy for stimulating OPC repopulation of demyelinating lesions that, as I will show, fails in the disease. Then, I will present our ongoing work based on the hypothesis that remyelination in MS fails due to metabolic deficit that prevents OPCs from synthesizing new myelin.
Time
(Friday) 12:00 - 13:00
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 Extracellular vesicles from mesenchymal stem cells reverse neuroinflammation and cognitive and motor impairment in rats with mild liver damage Cirrhotic patients may
Event Details
12:00 – 12:30 Gergana Mincheva
Extracellular vesicles from mesenchymal stem cells reverse neuroinflammation and cognitive and motor impairment in rats with mild liver damage
Cirrhotic patients may develop minimal hepatic encephalopathy (MHE), with mild cognitive impairment, psychomotor slowing and motor incoordination. Human mesenchymal stem cells derived extracellular vesicles (MSC-EVs) have been proposed as therapy for different diseases due to their immunomodulatory, anti-inflammatory and regenerative properties. The aim of this study was to assess if MSC-EVs reverse cognitive and motor impairment in rats with mild liver damage and identifying the underlying mechanisms. Mild liver damage was induced by intraperitoneal injection of CCl4 during four weeks. MSC-EVs were isolated from human adipose tissue-derived stem and were injected intravenously. We assessed cognitive and motor impairment with different behavioral tests, neuroinflammation and neurotransmission alterations were assessed by immunohistochemistry and Western Blot. MSC-EVs injected intravenously reduce neuroinflammation in hippocampus and cerebellum and reverse cognitive and motor impairment in rats with mid liver damage. This suggests that MSC-EVs are a promising therapy which could be used to improve MHE and the quality of life in cirrhotic patients.
12:30 – 13:00 Irene Soler
Unveiling transcriptomic sex differences of multiple sclerosis: an in silico atlas across cell types analysing scRNA-seq and snRNA-seq data
Multiple sclerosis (MS) is the leading cause of nontraumatic disability in young adults. Its major hallmark is myelin damage in the central nervous system, resulting in chronic neuroinflammation and neurodegeneration. Sex differences in the incidence, prevalence, disease progression, symptom variability, and response to treatment of MS have been reported. However, the molecular mechanisms underlying these differences remain poorly understood. The aim of this work is to exhaustively characterize sex bias in MS by cell type. To this end, we performed an in silico analysis of scRNA-seq and snRNA-seq data using the R programming language. First, we performed a systematic review in public repositories following the PRISMA guidelines. Three datasets were identified, each representing a different MS subtype. Then, we processed each selected dataset independently. After the annotation of the different cell types, all of them were fully characterized with the following analyses: differential gene expression, functional profiling, signaling pathways and cell-cell communication. In this seminar, we will focus on the secondary progressive MS subtype in nervous tissue, where the results obtained for astrocytes, microglia, neurons, oligodendrocytes, and oligodendrocyte precursor cells will be addressed
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
22may(may 22)19:0023(may 23)19:00Pint of Science 2023George Best Rock Club
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More Info: https://pintofscience.es/
Event Details
More Info: https://pintofscience.es/
Time
22 (Monday) 19:00 - 23 (Tuesday) 19:00
Location
George Best Rock Club
Carrer d'Alzira, 12
Organizer
Event Details
Thesis Title: Development of analytical procedures for the characterization of polypeptide-based nanoconjugates Author: Snežana Đorđević Supervisor: Prof. María J. Vicent Tutor: Prof. Ramon Martínez-Máñez Abstract: Due to the (poly)ionic and proteinic
Event Details
Thesis Title: Development of analytical procedures for the characterization of polypeptide-based nanoconjugates
Author: Snežana Đorđević
Supervisor: Prof. María J. Vicent
Tutor: Prof. Ramon Martínez-Máñez
Abstract:
Due to the (poly)ionic and proteinic nature of polypeptide-drug conjugates (PDCs), their translation “from bench to bedside” represents a complex and expensive undertaking, requiring reproducible and scalable polymerization techniques, the implementation of sophisticated analytical tools, exhaustive characterization steps, and the collection of detailed safety and efficacy data.
Classical techniques, such as liquid chromatography (LC) – UV/Vis and size exclusion chromatography (SEC) implemented in the quality control of PDCs during and after synthesis, cannot always support a qualitative and quantitative analysis of degradation products and metabolites. As an alternative, mass spectrometry (MS) and asymmetric flow field flow fractionation (AF4) have grown in influence on polypeptide and PDC characterization. The analysis of drug and degradation products/metabolites can take advantage of LC when coupled to MS. Meanwhile, AF4-mediated separation does not suffer from problems related to the interaction of the analyte with the column like in SEC; instead, AF4 applies a cross flow in an empty channel, which supports the “tailor-made” separation of molecules according to size and molecular weight.
The research included in this Ph.D. thesis focuses on developing new analytical procedures that will aid the selection of PDC candidates for further preclinical studies. We implemented an artificial intelligence tool (design of experiments) to develop analytical methods and optimize the synthesis of genipin-crosslinked PDCs. Moreover, we explored relatively new techniques, such as AF4 and mass spectrometry imaging, in developing novel single and combination PDCs and studying their biological fate in the search for efficient therapies for a range of diseases (advanced solid tumors, including triple negative breast, prostate, and pancreatic cancer, as well as spinal cord injury).
Time
(Wednesday) 11:30 - 13:30
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
Event Details
12:00 – 12:30 Milagros Buffa Targeting MCL-1 and BOK Interaction: Hit Compound Optimization and Mechanistic Insights for Cancer Therapy Finding new cancer therapies is critical to improve treatment
Event Details
12:00 – 12:30 Milagros Buffa
Targeting MCL-1 and BOK Interaction: Hit Compound Optimization and Mechanistic Insights for Cancer Therapy
Finding new cancer therapies is critical to improve treatment options and increasing patient survival. Dr. Mar Orzaez’s laboratory has discovered a hit compound for a new therapeutic target. In the outer mitochondrial membrane, induced myeloid leukemia cell differentiation protein (MCL1) and BCL2-related ovarian killer (BOK) interact through their transmembrane domains. Our hit compound, MBoIN 179, disrupts this interaction and releases BOK to induce cell death. To optimize the structure of our compound and learn more about its mechanism of action, we are performing several structural studies. Additionally, as a high overexpression of MCL-1 has been observed in lung tumours, we are performing functional experiments on 2D and 3D lung cancer models with our hit compound, to highlight the potential cell death effect of MBoIN 179.
Time
(Friday) 12:00 - 12:30
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
june
Event Details
Thesis Title: Pharmacological senolysis as a new therapeutic approach for the prevention of doxorubicin-induced cardiotoxicity Author: Araceli Lérida Viso PhD. Supervisors: Ramón Martínez Máñez, Dra. Alba García Fernández Summary: The
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Thesis Title: Pharmacological senolysis as a new therapeutic approach for the prevention of doxorubicin-induced cardiotoxicity
Author: Araceli Lérida Viso
PhD. Supervisors: Ramón Martínez Máñez, Dra. Alba García Fernández
Summary:
The present PhD thesis focuses on exploring the elimination of senescent cells (senolysis) in vitro and in vivo by administration of the senolytic drug, navitoclax, as a therapeutic option to prevent cardiotoxicity associated with antitumor treatment doxorubicin. Doxorubicin exposure severely affects the cardiac cell population in both mouse and human hearts by inducing premature senescence and navitoclax is one of the most potent and widely known senolytics in the field of cellular senescence, but its administration is associated with the occurrence of adverse effects, mainly thrombocytopenia.
In the first experimental section, we addressed the induction of senescence in an in vitro cardiomyocyte model and evaluated senolytic therapy as a therapeutic strategy. We also developed and characterized the nanoparticles targeting senescent cells and the navitoclax-based prodrug. The senolytic nanodevice is based on MSNs loaded with navitoclax and functionalized with a hexa-galacto-oligosaccharide (galactan). The prodrug is obtained after conjugation of navitoclax to an acetylated galactose molecule. In both cases, the mechanism of targeted therapy lies in the presence of the lysosomal enzyme ß-galactosidase, which is highly expressed in senescent cells. Upon entering the lysosome of senescent cells, the glycosidic bonds are hydrolyzed by the action of the enzyme, releasing the drug. The results show an increase in the therapeutic effect of the free drug.
Next, we developed a murine model of cardiotoxicity in which we demonstrated that systemic administration of doxorubicin induces the expression of markers of cardiotoxicity and senescence in the heart of treated mice and contributes to the deterioration of the cardiac function of the animals followed by echocardiography. In this preclinical model, the combined treatment of doxorubicin with the senolytic navitoclax, in the different formulations described above, leads to significant decrease in senescence and cardiotoxicity markers along with restoration of cardiac function. Similar results were observed with the three strategies mentioned: free drug, encapsulated drug, and prodrug formulation.
The scientific results presented in this thesis highlight the role of senescence in the progression of cardiotoxicity by doxorubicin administration and it is concluded that the senolytic systems evaluated here could be an important tool for the development of new therapeutic strategies in the field of prevention of therapy-associated side effects and represent an alternative to the limitations of current treatments.
Time
(Friday) 11:00 - 14:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain
Organizer
05jun10:0011:00Meet the Nobel Prize Dr. Joachim Frank
Event Details
Meet the Nobel Prize Speaker: Dr. Joachim Frank Place: Salón de Actos Jerónimo Forteza CIPF The Nobel Prize in Chemistry 2017 was awarded jointly to Jacques Dubochet, Joachim Frank and
Event Details
Meet the Nobel Prize
Speaker: Dr. Joachim Frank
Place: Salón de Actos Jerónimo Forteza CIPF
The Nobel Prize in Chemistry 2017 was awarded jointly to Jacques Dubochet, Joachim Frank and Richard Henderson “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”
Time
(Monday) 10:00 - 11:00
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
Organizer
july
07jul12:0013:00SEMINAR: María Ángeles Juanes / Maria Ibáñez Vives
Event Details
12:00 – 12:30 María Ángeles Juanes 12:30 – 13:00 María Ibáñez Vives
Event Details
12:00 – 12:30 María Ángeles Juanes
12:30 – 13:00 María Ibáñez Vives
Time
(Friday) 12:00 - 13:00
Location
Centro de Investigación Príncipe Felipe
Eduardo Primo Yúfera, 3 Valencia Spain