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38
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Introduction
Current institution
Current position
- ACCREDITED RESEARCHER (R3A)
Additional affiliations
February 2019 - December 2022
Publications
Publications (38)
Despite being in the same pathway, mutations of KRAS and BRAF in colorectal carcinomas (CRCs) determine distinct progression courses. ZEB1 induces an epithelial-to-mesenchymal transition (EMT) and is associated with worse progression in most carcinomas. Using samples from patients with CRC, mouse models of KrasG12D and BrafV600E CRC, and a Zeb1-def...
The induction of major histocompatibility complex (MHC) class II proteins by interferon gamma (IFN-γ) in macrophages play an important role during immune responses. Here we explore the signaling pathways involved in the induction by IFN-γ of the MHC II transactivator (CIIta) required for MHC II transcriptional activation. Cyclophilin A (CypA) is re...
Objective:
Understand the role of ZEB1 in the tumour initiation and progression beyond inducing an epithelial-to-mesenchymal transition.
Design:
Expression of the transcription factor ZEB1 associates with a worse prognosis in most cancers, including colorectal carcinomas (CRCs). The study uses survival analysis, in vivo mouse transgenic and xeno...
The canonical Wnt pathway (TCF4/β-catenin) has important roles during normal differentiation and in disease. Some Wnt functions depend on signaling gradients requiring the pathway to be tightly regulated. A key Wnt target is the transcription factor ZEB1 whose expression by cancer cells promotes tumor invasiveness by repressing the expression of ep...
Ras mutations are frequent in cancer cells where they drive proliferation and resistance to apoptosis. However in primary cells, mutant Ras instead can cause oncogene-induced senescence, a tumor suppressor function linked to repression of the polycomb factor Bmi1, which normally regulates cell cycle inhibitory cyclin dependent kinase inhibitors (cd...
It is thought that genomic instability precipitated by Rb1 pathway loss rapidly triggers additional cancer gene mutations, accounting for rapid tumour onset following Rb1 mutation. However, recent whole-genome sequencing of retinoblastomas demonstrated little genomic instability, but instead suggested rapid epigenetic activation of cancer genes. Th...
Mantle cell lymphoma (MCL) is a B-cell malignancy characterized by a poor response to treatment and prognosis. Constitutive activation of different signaling pathways in subsets of MCLs, through genetic and/or nongenetic alterations, endows tumor cells with enhanced proliferation and reduced apoptosis. The canonical Wnt pathway (β-catenin/TCF-LEF),...
Rb1 restricts cell cycle progression and it imposes cell contact inhibition to suppress tumor outgrowth. It also triggers oncogene-induced senescence to block Ras mutation. Loss of the Rb1 pathway, which is a hallmark of cancer cells, then provides a permissive environment for Ras mutation, and Ras is sufficient for invasive tumor formation in Rb1...
Skeletal muscle development is orchestrated by the myogenic regulatory factor MyoD, whose activity is blocked in myoblasts
by proteins preventing its nuclear translocation and/or binding to G/C-centered E-boxes in target genes. Recent evidence indicates
that muscle gene expression is also regulated at the cis level by differential affinity for DNA...
Purpose:
Carcinoma cells enhance their invasive capacity through dedifferentiation and dissolution of intercellular adhesions. A key activator of this process is the ZEB1 transcription factor, which is induced in invading cancer cells by canonical Wnt signaling (β-catenin/TCF4). Tumor invasiveness also entails proteolytic remodeling of the peritum...
Cancer is a complex multistep process involving genetic and epigenetic changes that eventually result in the activation of oncogenic pathways and/or inactivation of tumor suppressor signals. During cancer progression, cancer cells acquire a number of hallmarks that promote tumor growth and invasion. A crucial mechanism by which carcinoma cells enha...
The immune system is the responsible for body integrity and prevention
of external invasion. On one side, nanoparticles are no triggers that
the immune system is prepared to detect, on the other side it is known
that foreign bodies, not only bacteria, viruses and parasites, but also
inorganic matter, can cause various pathologies such as silicosis,...
In most carcinomas, invasion of malignant cells into surrounding tissues involves their molecular reprogramming as part of an epithelial-to-mesenchymal transition (EMT). Mutation of the APC gene in most colorectal carcinomas (CRCs) contributes to the nuclear translocation of the oncoprotein β-catenin that upon binding to T-cell and lymphoid enhance...
The ZEB family of transcription factors regulates key factors during embryonic development and cell differentiation but their role in cancer biology has only more recently begun to be recognized. Early evidence showed that ZEB proteins induce an epithelial-to-mesenchymal transition linking their expression with increased aggressiveness and metastas...
E2F1-3 proteins appear to have distinct roles in progenitor cells and in differentiating cells undergoing cell cycle exit. However, the function of these proteins in paradigms of terminal differentiation that involve continued cell division has not been examined. Using compound E2F1/E2F2-deficient mice, we have examined the effects of E2F1 and E2F2...
Loss of E-cadherin is a key initial step in the transdifferentiation of epithelial cells to a mesenchymal phenotype, which occurs when tumor epithelial cells invade into surrounding tissues. Expression of the nuclear factor ZEB1 induces an epithelial-to-mesenchymal transition and confers a metastatic phenotype on carcinomas by repressing the E-cadh...
BCL6 is essential for normal antibody responses and is highly expressed in germinal centre B-cells. Constitutive expression due to chromosomal translocations or mutations of cis-acting regulatory elements contributes to diffuse large B-cell lymphoma. BCL6 expression is therefore tightly regulated in a lineage- and developmental-stage-specific manne...
Murine bone marrow macrophages were able to recognize gold nanoparticle peptide conjugates, while peptides or nanoparticles alone were not recognized. Consequently, in the presence of conjugates, macrophage proliferation was stopped and pro-inflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6, as well as nitric oxide synthase (NOS2) were in...
MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in innate immunity. This phosphatase inactivates ERK1/2, which are involved in two opposite functional activities of the macrophage, namely proliferation and activation. Here we found that although macrophage proliferation and activation induce MKP-1 with different kineti...
Macrophages that react against pathogenic organisms can also be activated with artificial nanometric units consisting of gold nanoparticles (Au NPs) with a peptide coating. Using bone marrow-derived macrophages, here we show that these cells have the capacity to recognize Au NPs once conjugated to two biomedically relevant peptides, the amyloid gro...
Macrophages have the capacity to proliferate in response to specific growth factors, such as macrophage-colony stimulating factor (M-CSF). In the presence of several cytokines and activating factors, macrophages undergo growth arrest, become activated, and participate in the development of an immune response. We have previously observed that activa...
Earlier work has shown that the transcription factor C/EBPα induced a transdifferentiation of committed lymphoid precursors into macrophages in a process requiring endogenous PU.1. Here we have examined the effects of PU.1 and C/EBPα on fibroblasts, a cell type distantly related to blood cells and akin to myoblasts, adipocytes, osteoblasts, and cho...
Macrophages perform essential functions in the infection and resolution of inflammation. IFN-gamma is the main endogenous macrophage Th1 type activator. The classical IFN-gamma signaling pathway involves activation of Stat-1. However, IFN-gamma has also the capability to activate members of the MAPK family. In primary bone marrow-derived macrophage...
In this work, we study the role of phosphorylation as a regulatory mechanism for the interaction between the E3 ubiquitin ligase ItchWW3 domain and two PPxY motifs of one of its targets, the Epstein-Barr virus latent membrane protein 2A. Whereas ligand phosphorylation only diminishes binding, domain phosphorylation at residue T30 abrogates it. We s...
Macrophages proliferate in the presence of their growth factor, macrophage colony-stimulating factor (M-CSF), in a process
that is dependent on early and short ERK activation. Lipopolysaccharide (LPS) induces macrophage activation, stops proliferation,
and delays ERK phosphorylation, thereby triggering an inflammatory response. Proliferating or act...
Voltage-dependent K(+) (Kv) channels are involved in the immune response. Kv1.3 is highly expressed in activated macrophages and T-effector memory cells of autoimmune disease patients. Macrophages are actively involved in T-cell activation by cytokine production and antigen presentation. However, unlike T-cells, macrophages express Kv1.5, which is...
The immunosuppressor sanglifehrin A (SfA) is a member of a family of immunophilin cyclophilin A-binding molecules and does not inhibit calcineurin activity. Sanglifehrin A inhibits M-CSF-dependent macrophage proliferation by arresting the G1 phase of the cell cycle but does not affect cell viability. This immunosuppressor exerts its action on proli...
Macrophages are key regulators of immune responses. In the absence of an activating signal, murine bone marrow-derived macrophages undergo proliferation in response to their specific growth factor, namely M-CSF. The addition of bacterial LPS results in macrophage growth arrest and their engagement in a proinflammatory response. Although participati...
Collaboration between the immunological and hormonal systems in females is crucial for basic cellular and molecular processes responsible for successful reproduction. The aim of this study was to evaluate the effect of estradiol and progesterone on the proliferation of bone marrow derived macrophages of BALB/c (H-2d) mice. Applying an in vitro mode...
Mouse bone marrow-derived macrophages proliferate in the presence of macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor, or IL-3, but undergo apoptosis in their absence. Inhibition of extracellular signal-regulated kinases (ERK)-1/2 blocks growth factor-dependent proliferation but not survival, indicating...
Voltage-dependent K+ channels (VDPC) are expressed in most mammalian cells and involved in the proliferation and activation of lymphocytes. However, the role of VDPC in macrophage responses is not well established. This study was undertaken to characterize VDPC in macrophages and determine their physiological role during proliferation and activatio...
Calcineurin is constitutively expressed in bone marrow-derived macrophages. However, macrophage response to macrophage colony-stimulating factor (M-CSF) was not impaired by the use of either calcineurin inhibitors (W-13, chlorpromazine and trifluoperazine), calcium chelators (BAPTA-AM) or Ca2+ channel antagonists (verapamil, nifedipine and diltiaze...
