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Human REXO4 is a poorly characterized exonuclease that is overexpressed in human cancers. To better understand the function of REXO4 and its relationship to cellular proliferation, we have undertaken multidisciplinary approaches to characterize its cell cycle phase-dependent subcellular localization and the cis determinants required for this localization, its importance to cell cycle progression and cell viability, its protein-protein association network, and its activity. We show that the localization of REXO4 to the nucleolus in interphase depends on an N-terminal nucleolar localization sequence and that its localization to the perichromosomal layer of mitotic chromosomes is dependent on Ki67. Depletion of REXO4 led to a G1/S cell cycle arrest, and reduced cell viability. REXO4 associated with ribosome components and other proteins involved in rRNA metabolism. We propose a model where REXO4 is important for proper rRNA processing, which is required for ribosome biogenesis, cell cycle progression, and proliferation. REXO4 is a putative RNA exonuclease with limited characterization. The authors used in silico, cell, and molecular biology approaches to characterize its localization, associations, regulation, and function. They found that during interphase, REXO4 localizes to the nucleolus through an N-terminal nucleolar localization sequence. Whereas during mitosis, REXO4 localized to the perichromosomal layer in a Ki67-dependent manner. REXO4 was required for proper cell cycle progression, and viability. These results indicated that REXO4 is important for regulating cell proliferation. 

Abstract Objective:Magnetic fluid hyperthermia (MFH) is a still experimental technique found to have a potential application in the treatment of cancer. The method aims to reach around 41 °C–47 °C in the tumor site by exciting magnetic nanoparticles with an externally applied alternating magnetic field (AMF), where cell death is expected to occur. Applying AMFs with high spatial resolution is still a challenge. The AMFs from current and prospective MFH applicators cover relatively large areas; being not suitable for patients having metallic implants near the treatment area. Thus, there will be a clinical need for smaller magnetic field applicators. To this end, a laparoscopic induction heater (LIH) and a transrectal induction heater (TRIH) were developed.Methods:Miniature ‘pancake’ coils were wound and inserted into 3D printed enclosures. Ovarian (SKOV-3, A2780) and prostate (PC-3, LNCaP) cancer cell lines were used to evaluate the instruments’ capabilities in killing cancer cellsin vitro, using Synomag^®-D nanoparticles as the heat mediators. NIH3T3 normal cell lines were also used with both devices to observe if these cells tolerated the conditions applied.Results:Magnetic field intensities reached by the LIH and TRIH were 42.6 kA m⁻¹at 326 kHz and 26.3 kA m⁻¹at 303 kHz, respectively. Temperatures reached in the samples were 41 °C by the LIH and 43 °C by the TRIH. Both instruments successfully accomplished killing cancer cells, with minimal effects on normal cells.Conclusion:This work presents the first line of handheld medical induction heaters and have the potential to be a complement to existing cancer therapies.Significance:These instruments could enable the development of MFH modalities that will facilitate the clinical translation of this thermal treatment. 

The elucidation of a protein’s interaction/association network is important for defining its biological function. Mass spectrometry–based proteomic approaches have emerged as powerful tools for identifying protein–protein interactions (PPIs) and protein–protein associations (PPAs). However, interactome/association experiments are difficult to interpret, considering the complexity and abundance of data that are generated. Although tools have been developed to identify protein interactions/associations quantitatively, there is still a pressing need for easy-to-use tools that allow users to contextualize their results. To address this, we developed CANVS, a computational pipeline that cleans, analyzes, and visualizes mass spectrometry–based interactome/association data. CANVS is wrapped as an interactive Shiny dashboard with simple requirements, allowing users to interface easily with the pipeline, analyze complex experimental data, and create PPI/A networks. The application integrates systems biology databases such as BioGRID and CORUM to contextualize the results. Furthermore, CANVS features a Gene Ontology tool that allows users to identify relevant GO terms in their results and create visual networks with proteins associated with relevant GO terms. Overall, CANVS is an easy-to-use application that benefits all researchers, especially those who lack an established bioinformatic pipeline and are interested in studying interactome/association data. 

I am deeply humbled and honored to receive the American Society for Cell Biology (ASCB) Prize for Excellence in Inclusivity. Thank you to the ASCB for recognizing the contributions of faculty to inclusion and diversity in STEM and the importance of this for the advancement of science. Thank you to the Howard Hughes Medical Institute (HHMI) for your generous support of inclusivity. The prize money will be used to fund outreach activities aimed at increasing inclusion in science and to create research opportunities for students from underrepresented groups in the sciences. In this essay, I share bits of my life’s story that I hope will resonate with a broad audience, especially students from underrepresented groups in STEM, and that drive my passion for inclusion and diversity. I provide points of consideration for students to enhance their preparation for science careers and for faculty to improve the current landscape of inclusion and diversity in STEM.