• Home
  • Natalia Rubinstein
Natalia Rubinstein

Natalia Rubinstein
Instituto de Biociencias Biotecnologia y Biologia Traslacional (iB3), Faculty of Exact Science, University of Buenos, Argentina

Researcher CONICET, Molecular Metastasis Lab

About

40
Publications
4,762
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,172
Citations
Additional affiliations
December 2019 - August 2020
Instituto de Biociencias, Biotecnologia y Biologia Traslacional (iB3)-Universidad de Buenos Aires
Position
  • Researcher
Description
  • Group leader of Molecular Mechanism of Metastasis Lab. Foundational member of iB3.
January 2016 - November 2019
IFIBYNE-CONICET
Position
  • Researcher
Description
  • Group leader Molecular Mechanism of Metastasis lab since 2017 at FCEN-UBA
January 2012 - January 2014
University of Basel
Position
  • PostDoc Position

Publications

Publications (40)
Article
Pygopus 2 (Pygo2) is a co-activator of Wnt/β-catenin signaling that can bind bi- or trimethylated lysine 4 of histone-3 (H3K4me2/3) and participate in chromatin reading and writing. It remains unknown whether the Pygo2- H3K4me2/3 association has a functional relevance in breast cancer progression in vivo. To investigate the functional relevance of...
Article
Despite the existence of tumor-specific immune cells, most tumors have devised strategies to avoid immune attack. We demonstrate here that galectin-1 (Gal-1), a negative regulator of T cell activation and survival, plays a pivotal role in promoting escape from T cell-dependent immunity, thus conferring immune privilege to tumor cells. Blockade of i...
Article
Full-text available
Runx1 participation in epithelial mammary cells is still under review. Emerging data indicates that Runx1 could be relevant for breast tumor promotion. However, to date no studies have specifically evaluated the functional contribution of Runx1 to control gene expression in mammary epithelial tumor cells. It has been described that Runx1 activity i...
Article
Full-text available
R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell-enriched compartment of normal mouse mammary gland...
Preprint
Full-text available
The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from SARS-CoV-2 Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell system. RBD obtained from both yeast and mammalian cell...
Article
Full-text available
The receptor binding domain (RBD) of the Spike protein from SARS-CoV-2 is a promising candidate to develop effective COVID-19 vaccines since it can induce potent neutralizing antibodies. We have previously reported the highly efficient production of RBD in Pichia pastoris , which is structurally similar to the same protein produced in mammalian HEK...
Article
Full-text available
Canonical Wnt/β-catenin signaling is an established regulator of cellular state and its critical contributions to tumor initiation, malignant tumor progression and metastasis formation have been demonstrated in various cancer types. Here, we investigated how the binding of β-catenin to the transcriptional coactivators B-cell CLL/lymphoma 9 (Bcl9) a...
Article
During malignant progression, epithelial cancer cells dissolve their cell–cell adhesion and gain invasive features. By virtue of its dual function, β-catenin contributes to cadherin-mediated cell–cell adhesion, and it determines the transcriptional output of Wnt signaling: via its N terminus, it recruits the signaling coactivators Bcl9 and Pygopus,...
Preprint
Full-text available
We covalently coupled the RBD domain of SARS-CoV-2 produced in Pichia pastoris to a decameric carrier to produce a potent immunogen
Preprint
Since the discovery of SARS-CoV-2, several antigens have been proposed to be part of COVID-19 vaccines. The receptor binding domain (RBD) of Spike protein is one of the promising candidates to develop effective vaccines since it can induce potent neutralizing antibodies. We previously reported the production of RBD in Pichia pastoris and showed it...
Article
Full-text available
The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell syste...
Article
Full-text available
The yeast Pichia pastoris is a cost-effective and easily scalable system for recombinant protein production. In this work we compared the conformation of the receptor binding domain (RBD) from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike protein expressed in P. pastoris and in the well established HEK-293T mammalian cell syste...
Article
Full-text available
Angiotensin (Ang) II, the main effector peptide of the renin-angiotensin system, has been implicated in multiple aspects of cancer progression such as proliferation, migration, invasion, angiogenesis and metastasis. Ang-(1-7), is a biologically active heptapeptide, generated predominantly from AngII by the enzymatic activity of angiotensin converti...
Article
Full-text available
Kaposi’s sarcoma (KS), a multifocal vascular neoplasm linked to human herpesvirus-8 (HHV-8/KS-associated herpesvirus [KSHV]) infection, is the most common AIDS-associated malignancy. Clinical management of KS has proven to be challenging because of its prevalence in immunosuppressed patients and its unique vascular and inflammatory nature that is s...
Article
Full-text available
Mechanisms accounting for the protection of the fetal semi-allograft from maternal immune cells remain incompletely understood. In previous studies, we showed that galectin-1 (Gal1), an immunoregulatory glycan-binding protein, hierarchically triggers a cascade of tolerogenic events at the mouse fetomaternal interface. Here, we show that Gal1 confer...
Article
Glucocorticoids influence post-natal mammary gland development by sequentially controlling cell proliferation, differentiation, and apoptosis. In the mammary gland, it has been demonstrated that glucocorticoid treatment inhibits epithelial apoptosis in post-lactating glands. In this study, our first goal was to identify new glucocorticoid target ge...
Article
It has been reported that R‐spondin3 (Rspo3) is a common insertion site for the viral genome in mouse mammary tumor virus (MMTV) induced‐mammary tumors and that HC11 cells over‐expressing this protein become tumorigenic when transplanted into mice. In addition, we have found that Rspo‐3 over‐expression is associated with loss of hormone regulation...
Article
Full-text available
Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary...
Article
Full-text available
Tumors escape from immune surveillance by producing immunosuppressive cytokines and proapototic factors, including TGF-beta and galectin-1 (Gal-1). Since immunosuppressive mechanisms might act in concert to confer tumor-immune privilege, we investigated the potential cross talk between TGF-beta and Gal-1 in highly metastatic mammary adenocarcinoma...
Article
Full-text available
Recent evidence indicates that protein-glycan interactions play a critical role in different events associated with the physiology of T-cell responses including thymocyte maturation, T-cell activation, lymphocyte migration and T-cell apoptosis. Glycans decorating T-cell surface glycoproteins can modulate T-cell physiology by specifically interactin...
Article
Full-text available
Apoptosis of cytotoxic T lymphocytes by herpes simplex virus type-1 (HSV-1) has been reported to be a relevant mechanism of viral immune evasion. Galectin-1 (Gal-1), an endogenous lectin involved in T-cell apoptosis, has recently gained considerable attention as a novel mechanism of tumor-immune evasion. Here we investigated whether infection of ce...
Article
Galectin-1 (Gal-1), a member of a family of highly conserved carbohydrate-binding proteins, has been reported to be a potent immunosuppressive and anti-inflammatory factor. It has been proposed that the presence of galectin-1 in organs such as the eye, the placenta, reproductive organs (testis, ovaries) and also in tumours might confer a status of...
Article
Recent evidence has implicated galectins and their carbohydrate ligands as novel regulators of T-cell homeostasis. Galectin-1 (Gal-1), a member of this family, inhibits clonal expansion, induces apoptosis of antigen-primed T lymphocytes and suppresses the development of T-cell-mediated autoimmune diseases in vivo. Because the beta-galactoside-bindi...
Article
Inflammation involves the sequential activation of signalling pathways leading to the production of both pro-inflammatory and anti-inflammatory mediators. Galectins constitute a family of structurally related beta-galactoside-binding proteins, which are defined by their affinity for poly-N-acetyllactosamine-enriched glycoconjugates and sequence sim...
Article
Galectins are a large family of structurally related beta-galactoside-binding proteins that play a pivotal role in the control of cell differentiation, proliferation, activation and apoptosis of many different cell types including immune cells. By crosslinking specific glycoconjugates, different members of the galectin family behave as pro-inflamma...
Article
Uncontrolled T-cell activation plays a critical role in the pathogenesis of inflammatory bowel diseases. Therefore, pharmacologic strategies directed to restore the normal responsiveness of the immune system by deleting inappropriately activated T cells could be efficacious in the treatment of these pathologic conditions. Galectin-1 is an endogenou...
Article
Galectin-1, a highly conserved beta-galactoside-binding protein, induces apoptosis of activated T cells and suppresses the development of autoimmunity and chronic inflammation. To gain insight regarding the potential role of galectin-1 as a novel mechanism of immune privilege, we investigated expression and ultrastructural localization of galectin-...
Article
Galectins are members of a highly conserved family of beta-galactoside-binding animal lectins. Presently, more than 14 members have been identified and additional homologues are likely to be discovered. Given their conservation throughout animal evolution, it is not surprising that they could play key roles in innate and adaptive immune responses,...
Article
Full-text available
Galectin-1, a beta-galactoside-binding protein expressed at sites of T-cell activation and immune privilege, has shown specific immunosuppressive properties. Because of the implications of this protein in T-cell tolerance and its potential use to avoid graft rejection, we investigated the immunosuppressive effects of galectin-1 in the course of the...
Article
Full-text available
Over the last decade, we have witnessed an explosion of information regarding the function of glycoconjugates, carbohydrate-binding proteins, and the elucidation of the sugar code. This progress has yielded not only important insights into fundamental areas of glycobiology but has also influenced other fields such as immunology and molecular medici...
Article
Galectin-1, a β-galactoside-binding protein expressed at sites of T-cell activation and immune privilege, has shown specific immunosuppressive properties. Because of the implications of this protein in T-cell tolerance and its potential use to avoid graft rejection, we investigated the immunosuppressive effects of galectin-1 in the course of the hu...
Article
Apoptosis of enterocytes is a feature that characterises the development of lesions in coeliac disease (CD). However, the intracellular pathways that lead to apoptosis of enterocytes have not been completely clarified. Bak is a member of the Bcl-2 family of proteins that acts as an endogenous promoter of apoptosis in normal enterocytes. However, it...
Article
We have demonstrated that a single low dose of cyclophosphamide has an antimetastatic effect on lymphoma (L-TACB)-bearing rats by modulating the host immune response. Galectin-1, a member of the galectin family with specificity for beta-galactosides, has potent immunomodulatory properties by regulating cell-matrix interactions and T-cell apoptosis....
Article
Galectins have emerged as a new family of closely related carbohydrate-binding proteins, which exert their functions by virtue of their ability to decipher glycocodes on complex glycoconjugates. They have been implicated in different immunological processes, such as lymphocyte adhesion, cytokine production, cell growth regulation, apoptosis and cen...
Article
Full-text available
Resumen Las galectinas constituyen una familia de proteínas extremadamente conservadas a través de la evolución. En función de su propiedad de descifrar glicocódigos específicos, estas proteínas han sido involucradas en un amplio espectro de eventos biológicos. Recientes avances han demostrado que estas proteínas juegan un rol fundamental en proces...

Questions

Questions (3)
Question
Do you advice to buy it?
Question
I would like to transfect them.
Question
I am trying to eliminate a gene on the mice mammary gland using also MMTV-PymT tumor mice line.

Projects

Projects (4)
Project
This project aims to conceptualize the subsystem of soy accumulation in Argentina through a socio-ecological systems approach, based on the integration of contributions from the social sciences (social and economic dimensions) as well as exact and natural sciences (environmental, ecological and biomedical dimensions, plus an axis that crosses the project transversally and that is the use of applied mathematics, specifically of computational modeling, simulation and physical information tools). For this, three specific objectives are proposed. The first objective is to analyze the main components of the system and their interactions as well as to perform an analysis of socio-ecological dynamics to identify the occurrence of socio-ecological traps based on the emergence of new technologies (gilded traps). The socio-territorial transformations that occurred from the transformations of the soy subsystem will be studied for this, investigating the processes of dialogue, negotiation and conflict around the use and appropriation of the territory and natural resources. Likewise, the impact of the soy subsystem will be evaluated in relation to changes in land use and the loss of natural capital, identifying the ecosystem services affected, as well as externalities that have a negative impact on its sustainability. The second objective is to identify the hierarchical relations of economic planning among the main actors of the soy subsystem, through a diagnosis of the main variables that affect the rate of profit of the different economic units (committed capital, conditions of access to credit, market position, innovation capacity and others). The third objective, on the other hand, tries to analyze if there are significant differences in the number of cases of cancer detected in populations close to areas of herbicide spraying compared to villages far from these areas, based on the use of data from rural populations of the province of Santa Fe. In a complementary way, the impact of different herbicides and formulations on cell viability and behavior will be studied through cellular and animal models, based on the use of fluorescent reporters and molecular markers for the activation of different stress, mitogenic, cell death and autophagy pathways in cultured cell lines and through experimental designs that allow the effect of these compounds on the consolidation, persistence and reconsolidation of memory in the crab model to be evaluated. The study of the soy accumulation subsystem from the interdisciplinary perspective proposed in this project will help to identify and suggest resolutions to tensions and incompatibilities present in the short, medium and long terms, between a) farming decisions of agricultural capital companies (which are based on maximization of their profit rates), b) the conservation and recovery of natural assets; c) the conservation and improvement of the population's health.
Project
Triple negative breast cancer (TNBC) is a type of cancer associated with early recurrence and low survival rate due to its high rate of metastasis. It does not express hormone receptors (estrogen and progesterone) and has lost the expression of the HER2/Neu gene. TNBC is associated with epithelial-mesenchymal transition (EMT), a process involved in the generation of more invasive cell phenotypes to promote metastasis, and that could be involved in the generation of chemotherapy resistance in breast tumors. Treatment options are limited by the lack of a specific therapeutic target, with standard chemotherapy being the only option available. In the search for prognostic markers in TNBC, it has been reported, among others, that the expression of the transcription factor Runx1 correlates with a worse prognosis in this group of patients. Although its functional biological relevance has not yet been elucidated, increasing evidence has demonstrated the potential involvement of this protein in the fate of normal and tumor mammary epithelial cells. Additionally, Runx1 was described to be mutated in breast tumors positive for hormone receptors but not in TNBC. It was shown that loss of Runx1 expression promotes EMT proposing this protein as a tumor suppressor factor in estrogen receptor positive human breast cancer lines. However, mice presenting Runx1 conditional knock-out in breast did not generate tumors, installing the need for more and deeper research to evaluate the participation of this transcription factor in the different subtypes of breast cancer. On the other hand, the protein kinase Akt (known as PKB) is also involved in the differentiation of breast tumors and in the acquisition of resistance to antitumor therapy. Deregulation of this pathway is associated with a wide variety of types of human cancer. Akt is indeed an attractive therapeutic target for cancer treatment and several specific Akt inhibitors have been found, some of which are being used in clinical trials. Interestingly, data published in immune lineage describe a cross-talk between Akt and Runx1 in which Runx1 regulates the Akt pathway. However, it has also been described that Akt1 is a Runx2 kinase. Finding an efficient therapy for TNBC patients is an unmet medical need and highlights the urgency of finding new prognostic markers and / or specific therapies. The general objective of our work is to study the functional interaction between Runx1 and Akt in the context of TNBC, as well as to establish whether the Akt pathway regulates the activity of this transcription factor and how it does so. We then established the following specific objectives (SO): SO1: Develop and study a network of protein-protein interactions that link Runx1 to the Akt pathway in silico. SO2: Evaluate the levels of expression, phosphorylation (activation), and localization of Akt and its substrates in cells with different levels of Runx1 activity. SO3: Evaluate the expression and activity of Runx1 in cells with different levels of Akt activity. SO4: Evaluate the role of Akt in TNBC-related processes: EMT and chemotherapy resistance.
Project
Framed under the same working hypothesis and objective of the previous project, this plan proposes the following specific objectives (SO): SO1: Evaluate, in different mammary tumor lines, the subcellular localization of Akt1 mutants which cannot be post-translationally modified in critical residues. SO2: Evaluate the phosphorylation pattern of Akt substrates in cells that express these mutants. SO3: Evaluate the effect of the overexpression of these mutants in apoptosis, proliferation, migration, epithelial-mesenchymal transition and resistance to antitumor drugs in each cell line analyzed in SO1. SO4: Evaluate, for cases where differences have been observed, if the same results are observed using Akt2 and Akt3 mutants or if there is specificity of isoforms.