p53 protects against genome instability following centriole duplication failure

Centriole function has been difficult to study because of a lack of specific tools that allow persistent and reversible centriole depletion. Here we combined gene targeting with an auxin-inducible degradation system to achieve rapid, titratable, and reversible control of Polo-like kinase 4 (Plk4), a master regulator of centriole biogenesis. Depletion of Plk4 led to a failure of centriole duplication that produced an irreversible cell cycle arrest within a few divisions. This arrest was not a result of a prolonged mitosis, chromosome segregation errors, or cytokinesis failure. Depleting p53 allowed cells that fail centriole duplication to proliferate indefinitely. Washout of auxin and restoration of endogenous Plk4 levels in cells that lack centrioles led to the penetrant formation of de novo centrioles that gained the ability to organize microtubules and duplicate. In summary, we uncover a p53-dependent surveillance mechanism that protects against genome instability by preventing cell growth after centriole duplication failure

A USP28-53BP1-p53-p21 signaling axis arrests growth after centrosome loss or prolonged mitosis

Precise regulation of centrosome number is critical for accurate chromosome segregation and the maintenance of genomic integrity. In nontransformed cells, centrosome loss triggers a p53-dependent surveillance pathway that protects against genome instability by blocking cell growth. However, the mechanism by which p53 is activated in response to centrosome loss remains unknown. Here, we have used genome-wide CRISPR/Cas9 knockout screens to identify a USP28-53BP1-p53-p21 signaling axis at the core of the centrosome surveillance pathway. We show that USP28 and 53BP1 act to stabilize p53 after centrosome loss and demonstrate this function to be independent of their previously characterized role in the DNA damage response. Surprisingly, the USP28-53BP1-p53-p21 signaling pathway is also required to arrest cell growth after a prolonged prometaphase. We therefore propose that centrosome loss or a prolonged mitosis activate a common signaling pathway that acts to prevent the growth of cells that have an increased propensity for mitotic errors

The appearance of Filipina nationalism: body, nation, empire

The main objective of my research is to investigate how gender and the body function in strategies and ideologies of nationalism and colonialism. This dissertation explores the connections between gendered embodiment and Filipina nationalism from 1898 to 1941. In both the colonial Philippines and the United States, Filipino women actively constructed their own national identities through the stylized presentation of their physical bodies in order to navigate through the multilayered power struggles and hierarchies created by intersecting Filipino nationalist and United States imperial projects. I specifically look at how colonial and nationalist projects used fashion, beauty regimens, and public spectacles to police Filipino women’s bodies, while Filipino women used these same arenas to construct identities that often contrasted with or rejected those imposed by colonial regimes. Ultimately, my project uses the lenses of local and global paradigms of race, gender, and sexuality to investigate the ways in which constructions of Filipina nationalism shaped the contours of Filipino America. My research on the Philippine-American colonial relationship serves as a critical call for transnational approaches to histories of U.S. empire—approaches that take the gendered, sexed and raced body into account. Colonial regimes maintained power through the racialization and sexualization of Filipinas, a process that promoted U.S. hierarchies of white supremacy and colonial authority. At the same time, Filipino anti-colonial nationalists relied on representations of Filipinas to challenge racist depictions and the denial of nationhood by displaying modern, civilized, and cultured qualities. Lastly, my findings reveal that women were not merely passive victims of colonization or accessories to Filipino male nationalists’ goals. Rather, my research shows that Filipinas decidedly used the concept of Filipina nationalism to define their roles and identities within the context of U.S. empire and the struggle for a Philippine nation

Discovery and Elucidation of Novel Regulators of Cell Division

Mitotic cell division is a process requiring a highly coordinated dance between many enzymes, substrates and metabolites to result in the segregation of identical sets of daughter chromosomes. A hallmark of cancer is the ability to perturb this process in ways that increase the proliferation of cancer cells. We have studied several aspects of cellular division in order to further elucidate how cancer cell progression can occur in human disease. Mammalian cell division is a biological process that has been studied for decades and important discoveries often coincide with the development of noveltools and techniques. I have developed a new cell-based high-throughput screening tool that combines CRISPR/Cas9 technology with the Fluorescence Ubiquitin Cell Cycle Indicator system (FUCCI) for assessing the cell cycle effects of knocking out genes of interest. This tool provides a genome-encoded cell cycle phase indicator system and dox-inducible Cas9 for use with guide RNA libraries for future screens. Many of the proteins our lab studies were initially identified through either proteomic analysis or genomic screening. While these approaches have yielded interesting hits, they have focused exclusively on protein-based regulation of cell cycle progression and division. To this end we performed a high-throughput screen of 1,200 different naturally occurring metabolites in order to find novel affectors of the cell cycle and have identified 180 putative. These results will provide the basis for future projects analyzing these metabolites and their roles in cell cycle regulation. Ribosome biogenesis has long been linked to cell proliferation and in my studies, I characterized Rexo4, an exonuclease responsible for processing nascent ribosomal RNA. Recent studies suggest that Rexo4 is a biomarker for cancer disease and is seen to be upregulated in cancer cells at both the mRNA and protein level. My work has determined that Rexo4 is a requirement for cell cycle progression in mammalian cells and that both its nucleolar localization and exonuclease activity are required for cell proliferation

Among things weightless

Among Things Weightless, as a collection of poems, attempts to enact the deliverance of the self through the difficult by following multiple speakers and their connections and disconnections to their respective worlds. It is composed of three lyric sequences which, in fragments, aim to map the experience of difficulty, uncertainty, and displacement. The first sequence, Aphasia, is a lyric sequence that contemplates on the difficulty of speaking as a mode of connection to the world and to the self. Another Morning, the second sequence, inquires on mans nature after being told to be created from the likeness of a divine being which is characterized as inherently good. Through a series of fragmented lyrics, it aims to enact the apparent tendency or penchant of man for evil in his struggle to realize the goodness he ultimately doesn\u27t have. Adrift is inspired by films such as Gravity, Upside Down, and Interstellar. It takes on the experience of floating and drifting in space as a metaphor for the paradoxes of human connection and disconnection. The introductory essay On Writing Among Things Weightless explores the writers education and formative poetics among others which informs the writing of the collection

Discovery and Elucidation of Novel Regulators of Cell Division

Mitotic cell division is a process requiring a highly coordinated dance between many enzymes, substrates and metabolites to result in the segregation of identical sets of daughter chromosomes. A hallmark of cancer is the ability to perturb this process in ways that increase the proliferation of cancer cells. We have studied several aspects of cellular division in order to further elucidate how cancer cell progression can occur in human disease. Mammalian cell division is a biological process that has been studied for decades and important discoveries often coincide with the development of noveltools and techniques. I have developed a new cell-based high-throughput screening tool that combines CRISPR/Cas9 technology with the Fluorescence Ubiquitin Cell Cycle Indicator system (FUCCI) for assessing the cell cycle effects of knocking out genes of interest. This tool provides a genome-encoded cell cycle phase indicator system and dox-inducible Cas9 for use with guide RNA libraries for future screens. Many of the proteins our lab studies were initially identified through either proteomic analysis or genomic screening. While these approaches have yielded interesting hits, they have focused exclusively on protein-based regulation of cell cycle progression and division. To this end we performed a high-throughput screen of 1,200 different naturally occurring metabolites in order to find novel affectors of the cell cycle and have identified 180 putative. These results will provide the basis for future projects analyzing these metabolites and their roles in cell cycle regulation. Ribosome biogenesis has long been linked to cell proliferation and in my studies, I characterized Rexo4, an exonuclease responsible for processing nascent ribosomal RNA. Recent studies suggest that Rexo4 is a biomarker for cancer disease and is seen to be upregulated in cancer cells at both the mRNA and protein level. My work has determined that Rexo4 is a requirement for cell cycle progression in mammalian cells and that both its nucleolar localization and exonuclease activity are required for cell proliferation

Preferences of Filipino Consumers on Personal Hygiene Products: An Inside Look on Traditional and Sustainable Options

The sustainability trend in the market requires businesses to change their usual models and mechanisms of producing goods to cater to consumer preferences. These preferences mainly revolve around the product\u27s brand, price, and accessibility, impacting consumers\u27 choices, priorities, and decisions (Gutierrez & Seva, 2016; Rappler, 2013; Longo et al., 2019). This study investigated more in-depth factors affecting an individual\u27s purchase and non-purchase of sustainable personal hygiene products in the market: bamboo toothbrushes and shampoo bars. For the grounded theory inquiry, participants ages 16-20 from the National Capital Region of the Philippines were recruited. Semi-structured interviews were conducted asking about their product preferences considering the initial categories: general questions, knowledge, price, effectiveness, culture, tradition, brand, social influence, availability, and other miscellaneous questions. All 12 participants\u27 interviews contributed to summarizing the study\u27s codes and categories. For the secondary analysis, the thematic analysis revealed two overarching themes characterizing the elements impacting one\u27s purchase and non-purchase of sustainable personal hygiene products: (1) barriers to accessing sustainable products; and (2) factors influencing an individual\u27s purchasing consideration of personal hygiene products. Enterprises might find it helpful to explore these themes to create business models best tailored to the market