Shulamit Sebban's research while affiliated with Hebrew University of Jerusalem and other places

Publications (26)

Article
Full-text available
Following fertilization, it is only at the 32-64-cell stage when a clear segregation between cells of the inner cell mass and trophectoderm is observed, suggesting a ‘T’-shaped model of specification. Here, we examine whether the acquisition of these two states in vitro, by nuclear reprogramming, share similar dynamics/trajectories. Using a compara...
Article
Full-text available
Vav1 is normally and exclusively expressed in the hematopoietic system where it functions as a specific GDP/GTP nucleotide exchange factor (GEF), firmly regulated by tyrosine phosphorylation. Mutations and overexpression of Vav1 in hematopoietic malignancies, and in human cancers of various histologic origins, are well documented. To reveal whether...
Preprint
Full-text available
Recent studies demonstrated that human trophoblast stem-like cells (hTS-like cells) can be derived from naïve embryonic stem cells or be induced from somatic cells by the pluripotency factors, OSKM. This raises two main questions; (i) whether human induced TSCs (hiTSCs) can be generated independently to pluripotent state or factors and (ii) what ar...
Preprint
Full-text available
Following fertilization, totipotent cells divide to generate two compartments in the early embryo: the inner cell mass (ICM) and trophectoderm (TE). It is only at the 32-64 -cell stage when a clear segregation between the two cell-types is observed, suggesting a ‘T’-shaped model of specification. Here, we examine whether the acquisition of these tw...
Article
Full-text available
In vitro assays for clustered DNA lesions will facilitate the analysis of the mechanisms underlying complex genome rearrangements such as chromothripsis, including the recruitment of repair factors to sites of DNA double‐strand breaks. We present a novel method generating localized DNA double‐strand breaks using UV‐irradiation with photomasks. The...
Article
Full-text available
To explore the contribution of Vav1, a hematopoietic signal transducer, to pancreatic ductal adenocarcinoma (PDAC) development, we generated transgenic mouse lines expressing, Vav1, K-Ras G12D , or both K-Ras G12D and Vav1 in pancreatic acinar cells. Co-expression of Vav1 and K-Ras G12D synergistically enhanced acinar-to-ductal metaplasia (ADM) for...
Preprint
In vitro assays for clustered DNA lesions will facilitate the analysis of the mechanisms underlying complex genome rearrangements such as chromothripsis, including the recruitment of repair factors to sites of DNA double-strand breaks. We present a novel method generating localized DNA double-strand breaks using UV-irradiation with photomasks. The...
Article
Full-text available
Following fertilization, totipotent cells undergo asymmetric cell divisions, resulting in three distinct cell types in the late pre-implantation blastocyst: epiblast (Epi), primitive endoderm (PrE), and trophectoderm (TE). Here, we aim to understand whether these three cell types can be induced from fibroblasts by one combination of transcription f...
Conference Paper
Full-text available
Introduction The overall 5 year survival rate of Pancreatic Ductal Adenocarcinoma (PDAC) is less than 5% and has remained stubbornly unchanged long time ago, despite the efforts in preclinical and clinical science. PDAC, the main form of pancreatic cancer, develops via acinar-ductal metaplasia (ADM) and neoplastic precursor lesions, such as pancrea...
Article
How the first cell fate decision of an embryo occurs is one of the most fascinating biological questions examined over the last few decades, with numerous in vivo models proposed and many factors tested for their role in the process. In this review, we will primarily focus on the mouse model and discuss the role that transcription factors play duri...
Article
The generation of induced pluripotent stem cells (iPSCs) and directly converted cells holds great promise in regenerative medicine. However, after in-depth studies of the murine system, we know that the current methodologies to produce these cells are not ideal and mostly yield cells of poor quality that might hold a risk in therapeutic application...
Article
Full-text available
Induced pluripotent stem cells (iPSCs) undergo extensive nuclear reprogramming and are generally indistinguishable from embryonic stem cells (ESCs) in their functional capacity and transcriptome and DNA methylation profiles. However, direct conversion of cells from one lineage to another often yields incompletely reprogrammed, functionally compromi...
Article
Full-text available
Vav1 is a signal transducer that functions as a scaffold protein and a regulator of cytoskeleton organization in the hematopoietic system, where it is exclusively expressed. Recently, Vav1 was shown to be involved in diverse human cancers, including lung cancer. We demonstrate that lung cancer cells that abnormally express Vav1 secrete growth facto...
Data
Vav1 expression in MCF-7 cells following treatment with estradiol. MCF-7 cells were treated for 48 hr with 0, 10 and 20 nM of estrodiol (SIGMA). cDNA was subjected to RT-PCR using Vav1 primers. Actin was used as a loading control. (TIF)
Article
Full-text available
Vav1 functions as a signal transducer protein in the hematopoietic system, where it is exclusively expressed. Vav1 was recently implicated in several human cancers, including lung, pancreatic and neuroblasoma. In this study, we analyzed the expression and function of Vav1 in human breast tumors and breast cancer cell lines. Immunohistochemical anal...
Data
Antibodies used for Immunoprecipitation, Immunoblotting, Immunohistochemistry and Immunofluorescence. The antibodies for western blotting, immunoprecipitation, immunohistochemistry and immunofluorescence used in the study are detailed, including the source for their purchase. (DOC)
Data
Vav1 (mRNA and protein) and Cbl-c (mRNA) expression in various breast cancer cell lines. The mRNA and protein expression level of Vav1 and mRNA expression of Cbl-c as assessed in our experiments (−; +/−; ++) in various human breast cancer cell lines used in our experiments. (XLS)
Data
Primers used for Real-Time PCR and shRNA sequences. This table details the sequences of primers used for Real-Time PCR performed. Also, included are the sequences used for shRNA. (DOC)
Data
Vav1 expression in breast cancer tissue array. The table details the various cancer tissues used in the study including their receptor expression (ER, PR, and HER2 from – to +++) and cancer staging (TNM) according to the manufecturere's information. Also, included is the level of Vav1 protein expression calculated as detailed in the Material and Me...
Article
Full-text available
We previously found LOXL4 to be alternatively spliced in an anatomic site-specific manner in tumors involving the serosal cavities. LOXL4 splice variants were predominantly or exclusively expressed in effusion specimens from ovarian and breast carcinoma patients, and were absent in primary carcinomas. In the present study, LOXL4 full-length or spli...
Article
Introduction: Lysyl oxidase (LOX) is an amine oxidase that is usually synthesized and secreted by fibrogenic cells. Four LOX-like (LOXL) genes have been identified so far in mammalian genomes, encoding four different LOX-like proteins: LOXL1, LOXL2, LOXL3 and LOXL4. All members of the LOX family show a highly conserved C-terminus region that contai...
Article
Lysyl oxidase-like enzymes (LOXL) are expressed in various cancers. We analyzed the expression of LOXL2, LOXL3, and LOXL4 in cancers involving the serosal cavities-breast carcinoma, ovarian carcinoma, and malignant mesothelioma using reverse-transcriptase polymerase chain reaction. We discovered two new alternative splice variants of LOXL4. The spl...

Citations

... Our results clearly demonstrated that Vav1 and K-Ras G12D synergize in enhancing tumor development, probably due to increase in Vav1's activity as a GDP/GTP exchange factor in the Vav1/K-Ras G12D mice [36]. While expression of Vav1 in the pancreatic transgenic mouse model did not elicit any tumorigenicity when expressed on its own, we demonstrated that ubiquitous expression of Vav1 via the ROSA26 promoter led to the development of B-cell lymphomas [37]. ...
... Several studies have demonstrated the therapeutic potential of inhibiting the guanine nucleotide exchange factor, VAV1 protein [8,9], as a possible treatment for several types of cancer including lung cancer [10], breast cancer [11,12], glioblastoma [13], hematological malignancies [14], and PC [15][16][17]. The protein is normally expressed in the hematopoietic system, where it regulates the development and activation of immune cells [8,18]. ...
... This identified 15,119 unique ZFP266 binding sites (Fig. 4A), predominantly situated in introns or intergenic regions ( Supplementary Fig. 5A, Supplementary Data 9). These ZFP266 binding sites have low chromatin accessibility as measured by ATAC-seq in MEFs, 72 h after reprogramming, as well as in iPSCs 39 (Fig. 4A). ZFP266 binding sites were predominantly enriched for somatic AP-1 TF motifs (Fig. 4B), and little OSKM binding was observed at the same loci in 48 hr reprogramming or ESC ChIP-Seq datasets 40,41 (Supplementary Figure 5B, C). ...
... Our data suggest that OEC EVs promote the expression of reprogramming genes, such as POU5F1, SOX2, NANOG, KLF4 and C-MYC, in embryos. Reprogramming genes have been implicated in the early implantation of embryos and in the proliferation and differentiation of inner cell masses [43,44]. At the same time, we found that OEC EVs could promote the expression of TEAD4 and CDX2. ...
... Previous studies have shown that transplanting human embryo-derived neural stem cells 3 or mouse-induced pluripotent stem cell (iPSC)-derived neural stem cells 4 into HD transgenic (TG) mice promoted neuronal or astrocytic differentiation with functional benefits. Patient-specific iPSCs are a potentially renewable source of autologous cells for stem cell therapy that will not induce immune rejection [5][6][7] . However, iPSCs derived from patients with genetic diseases carry the mutation. ...
... Cells that are isolated from the ICM can be cultivated as embryonic (E)SCs, defined by their ability to differentiate into all adult cell types [3], hence pluripotent (P)SCs. Cells isolated from the trophectoderm give rise to the placenta [4,5], and can be cultivated as trophoblast (T)SCs. Importantly, the low accessibility of early embryos, the paucity of embryonic material, and the technical difficulties in direct experimental manipulation in vivo, underscore the necessity of cell models for the study of early development [6]. ...
... Several studies have demonstrated the therapeutic potential of inhibiting the guanine nucleotide exchange factor, VAV1 protein [8,9], as a possible treatment for several types of cancer including lung cancer [10], breast cancer [11,12], glioblastoma [13], hematological malignancies [14], and PC [15][16][17]. The protein is normally expressed in the hematopoietic system, where it regulates the development and activation of immune cells [8,18]. ...
... Interestingly, Vav1 was originally isolated as an in vitro-activated oncogene (Katzav et al., 1989) and has been implicated in breast cancer (Du et al., 2014), pancreatic adenocarcinoma, melanoma, and lung cancer (Fernandez-Zapico et al., 2005;Bartolome et al., 2006;Lazer et al., 2009). Although it has been reported that MCF7 cells lack expression of Vav1 and that its overexpression stimulates apoptosis (Sebban et al., 2013), we analyzed the online database and confirmed the expression of all Vav isoforms in MCF7 cells FIGURE 3: BPGAP1 interacts with inactive Rac1 and promotes Rac1 activation. (A) BPGAP1 is required for Rac1 activation. ...
... LOXL4 encodes a copper-dependent amine oxidase that is involved in the formation of crosslinks in collagens and elastin and is a potential drug target for the treatment of head and neck squamous cell carcinoma, where it is differentially expressed between tumor and normal tissue [63,64]. LOXL4 is also known to promote proliferation and metastasis of gastric cancers and breast cancer [65,66]. ADAM19 is a member of the ADAM family (a disintegrin and metaloprotease domain) and is known to be involved in fertilization, muscle development, and neurogenesis but also in cell-cell and cell-matrix interactions. ...
... Furthermore, LOXL3 maintains genomic stability in melanoma by association with oncogenic BRAF in melanogenesis and promotes sustained proliferation [17]. It is also upregulated in various tumors, such as gastric cancer cells, breast cancer, myeloproliferative neoplasms, ovarian carcinoma, and colorectal cancer [13,[18][19][20][21][22], suggesting that it may be a target candidate for the treatment of tumors. ...