Elsa Logarinho - Academia.edu (original) (raw)

Papers by Elsa Logarinho

Journal of Cell Biology, Dec 16, 2013

Chromosome Research, Feb 15, 2021

CLASPs are key modulators of microtubule dynamics throughout the cell cycle. During mitosis, CLAS... more CLASPs are key modulators of microtubule dynamics throughout the cell cycle. During mitosis, CLASPs independently associate with growing microtubule plus-ends and kinetochores and play essential roles in chromosome segregation. In a proteomic survey for human CLASP1-interacting proteins during mitosis, we have previously identified SOGA1 and SOGA2/MTCL1, whose mitotic roles remained uncharacterized. Here we performed an initial functional characterization of human SOGA1 and SOGA2/MTCL1 during mitosis. Using specific polyclonal antibodies raised against SOGA proteins we confirmed their expression and reciprocal interaction with CLASP1 and CLASP2 during mitosis. In addition, we found that both SOGA1 and SOGA2/MTCL1 are phospho-regulated during mitosis by CDK1. Immunofluorescence analysis revealed that SOGA2/MTCL1 co-localizes with mitotic spindle microtubules and spindle poles throughout mitosis and both SOGA proteins are enriched at the midbody during mitotic exit/cytokinesis. GFP-tagging of SOGA2/MTCL1 further revealed a microtubule-independent localization at kinetochores. Live-cell imaging after siRNA-mediated knockdown of SOGA1 and SOGA2/MTCL1 showed that they are independently required for distinct aspects of chromosome segregation. Thus, SOGA1 and SOGA2/MTCL1 are bona fide CLASP-interacting proteins during mitosis required for faithful chromosome segregation in human cells.

Advances in Experimental Medicine and Biology, 2017

Aging is a biological process characterized by the progressive deterioration of physiological fun... more Aging is a biological process characterized by the progressive deterioration of physiological functions known to be the main risk factor for chronic diseases and declining health. There has been an emerging connection between aging and aneuploidy, an aberrant number of chromosomes, even though the molecular mechanisms behind age-associated aneuploidy remain largely unknown. In recent years, several genetic pathways and biochemical processes controlling the rate of aging have been identified and proposed as aging hallmarks. Primary hallmarks that cause the accumulation of cellular damage include genomic instability, telomere attrition, epigenetic alterations and loss of proteostasis (López-Otín et al., Cell 153:1194-1217, 2013). Here we review the provocative link between these aging hallmarks and the loss of chromosome segregation fidelity during cell division, which could support the correlation between aging and aneuploidy seen over the past decades. Secondly, we review the systemic impacts of aneuploidy in cell physiology and emphasize how these include some of the primary hallmarks of aging. Based on the evidence, we propose a mutual causality between aging and aneuploidy, and suggest modulation of mitotic fidelity as a potential means to ameliorate healthy lifespan.

eLife, May 5, 2015

Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, ... more Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome.

Supplemental movie 2 shows live imaging to measure the cell cycle and mitotic duration in RCM-1-t... more Supplemental movie 2 shows live imaging to measure the cell cycle and mitotic duration in RCM-1-treated Rd76-9 cells.

Stem Cells Translational Medicine, Aug 13, 2022

Different animal models have been used for hair research and regeneration studies based on the si... more Different animal models have been used for hair research and regeneration studies based on the similarities between animal and human skins. Primary knowledge on hair follicle (HF) biology has arisen from research using mouse models baring spontaneous or genetically engineered mutations. These studies have been crucial for the discovery of genes underlying human hair cycle control and hair loss disorders. Yet, researchers have become increasingly aware that there are distinct architectural and cellular features between the mouse and human HFs, which might limit the translation of findings in the mouse models. Thus, it is enticing to reason that the spotlight on mouse models and the unwillingness to adapt to the human archetype have been hampering the emergence of the long-awaited human hair loss cure. Here, we provide an overview of the major limitations of the mainstream mouse models for human hair loss research, and we underpin a future course of action using human cell bioengineered models and the emergent artificial intelligence.

Dermatologic Surgery, Dec 1, 2019

BACKGROUND Appropriate storage of human hair follicle (HF) grafts during follicular unit excision... more BACKGROUND Appropriate storage of human hair follicle (HF) grafts during follicular unit excision (FUE) is crucial toward successful hair shaft implantation. Several commercial storage solutions are currently used to ensure ex vivo maintenance of follicular grafts viability and trichogenicity. However, quantitative experimental evidence demonstrating molecular changes in HF cells associated with the usage of different storage solutions is largely missing. OBJECTIVE To identify gene expression changes in HF cells caused by ex vivo storage of hair grafts in different preservation conditions. METHODS The authors performed gene expression analysis in dermal papilla (DP) isolated from HF stored under different temperatures and solutions. The expression signature of key genes controlling hair growth and cycling, apoptosis, inflammation, and senescence was assessed for (1) chilled versus room temperature (RT) and (2) DP cell medium, saline, Hypothermosol, platelet-rich plasma, and ATPv-supplemented saline.

International Journal of Molecular Sciences, Apr 1, 2021

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Journal of Cell Science, Jul 1, 1996

The casein kinase 1α gene of Drosophila melanogaster is developmentally regulated and the kinase ... more The casein kinase 1α gene of Drosophila melanogaster is developmentally regulated and the kinase activity of the protein induced by DNA damage

Journal of Cell Science, Oct 1, 1998

The Drosophila POLO kinase localises to multiple compartments of the mitotic apparatus and is req... more The Drosophila POLO kinase localises to multiple compartments of the mitotic apparatus and is required for the phosphorylation of MPM2 reactive epitopes

Cells, May 18, 2021

Molecular Cancer Therapeutics, Jul 1, 2019

The oncogenic transcription factor FOXM1 has been previously shown to play a critical role in car... more The oncogenic transcription factor FOXM1 has been previously shown to play a critical role in carcinogenesis by inducing cellular proliferation in multiple cancer types. A small-molecule compound, Robert Costa Memorial drug-1 (RCM-1), has been recently identified from high-throughput screen as an inhibitor of FOXM1 in vitro and in mouse model of allergen-mediated lung inflammation. In the present study, we examined antitumor activities of RCM-1 using tumor models. Treatment with RCM-1 inhibited tumor cell proliferation as evidenced by increased cell-cycle duration. Confocal imaging of RCM-1-treated tumor cells indicated that delay in cellular proliferation was concordant with inhibition of FOXM1 nuclear localization in these cells. RCM-1 reduced the formation and growth of tumor cell colonies in the colony formation assay. In animal models, RCM-1 treatment inhibited growth of mouse rhabdomyosarcoma Rd76-9, melanoma B16-F10, and human H2122 lung adenocarcinoma. RCM-1 decreased FOXM1 protein in the tumors, reduced tumor cell proliferation, and increased tumor cell apoptosis. RCM-1 decreased protein levels and nuclear localization of b-catenin, and inhibited protein-protein interaction between b-catenin and FOXM1 in cultured tumor cells and in vivo. Altogether, our study provides important evidence of antitumor potential of the small-molecule compound RCM-1, suggesting that RCM-1 can be a promising candidate for anticancer therapy.

Nature Cell Biology, May 1, 2014

Mitotic spindle bipolarity is essential for faithful segregation of chromosomes during cell divis... more Mitotic spindle bipolarity is essential for faithful segregation of chromosomes during cell division. Multipolar spindles are often seen in human cancers and are usually associated with supernumerary centrosomes that result from centrosome overduplication or cytokinesis failure. A less-understood path to multipolar spindle formation may arise due to loss of spindle pole integrity in response to spindle and/or chromosomal forces. Here we discuss the different routes leading to multipolar spindle formation, focusing on spindle multipolarity without centrosome amplification. We also present the distinct and common features between these pathways and discuss their therapeutic implications.

Chemistry & Biology, Jun 1, 2011

Centromere Protein E (CENP-E) is a kinetochore-associated motor protein of the kinesin-7 family. ... more Centromere Protein E (CENP-E) is a kinetochore-associated motor protein of the kinesin-7 family. During mitosis, cells use the ATPase activity of CENP-E to slide misaligned chromosomes along spindle microtubules toward the equator and establish the metaphase plate prior to chromosome segregation. In addition to its requirement as a molecular motor for chromosome motion, we have recently reported a motor-independent role of CENP-E in the recruitment of CLIP-associated proteins (CLASPs) to kinetochores, thereby promoting turnover and poleward flux of attached microtubules (Maffini et al., 2009). This conclusion was drawn in part after the use of a small molecule called UA62784 that had been isolated from a high-throughput cytotoxicity screen against pancreatic cancer cells and was reported to be a specific inhibitor of the ATPase activity of CENP-E (Henderson et al., 2009).

ABSTRACTAging is characterized by changes in gene expression that drive deleterious cellular phen... more ABSTRACTAging is characterized by changes in gene expression that drive deleterious cellular phenotypes leading to senescence. The transcriptional activation of senescence genes has been mainly attributed to epigenetic shifts, but the changes in chromatin accessibility and its underling mechanisms remain largely elusive in natural aging. Here, we profiled chromatin accessibility in human dermal fibroblasts (HDFs) from neonatal and octogenarian individuals. We found that AP-1 binding motifs are prevalent in elderly specific accessible regions of the chromatin while neonatal-specific regions are highly enriched for TEAD binding motifs. We further show thatTEAD4andFOXM1share a conserved transcriptional regulatory landscape controlled by an age-dependent enhancer that closes with aging and drives senescence when deleted. Finally, we demonstrate thatFOXM1ectopic expression in elderly cells partially resets chromatin accessibility to a youthful state due to FOXM1 repressive function in th...

Supplemental movie 5 shows live imaging to measure the cell cycle and mitotic duration in Vehicle... more Supplemental movie 5 shows live imaging to measure the cell cycle and mitotic duration in Vehicle-treated MyC-CaP cells.