Lesson Learned from Collecting Quantified Self Information via Mobile and Wearable Devices

The ubiquity and affordability of mobile and wearable devices has enabled us to continually and digitally record our daily life activities. Consequently, we are seeing the growth of data collection experiments in several scientific disciplines. Although these have yielded promising results, mobile and wearable data collection experiments are often restricted to a specific configuration that has been designed for a unique study goal. These approaches do not address all the real-world challenges of “continuous data collection” systems. As a result, there have been few discussions or reports about such issues that are faced when “implementing these platforms” in a practical situation. To address this, we have summarized our technical and user-centric findings from three lifelogging and Quantified Self data collection studies, which we have conducted in real-world settings, for both smartphones and smartwatches. In addition to (i) privacy and (ii) battery related issues; based on our findings we recommend further works to consider (iii) implementing multivariate reflection of the data; (iv) resolving the uncertainty and data loss; and (v) consider to minimize the manual intervention required by users. These findings have provided insights that can be used as a guideline for further Quantified Self or lifelogging studies

Mutant p53 as a guardian of the cancer cell

Forty years of research have established that the p53 tumor suppressor provides a major barrier to neoplastic transformation and tumor progression by its unique ability to act as an extremely sensitive collector of stress inputs, and to coordinate a complex framework of diverse effector pathways and processes that protect cellular homeostasis and genome stability. Missense mutations in the TP53 gene are extremely widespread in human cancers and give rise to mutant p53 proteins that lose tumor suppressive activities, and some of which exert trans-dominant repression over the wild-type counterpart. Cancer cells acquire selective advantages by retaining mutant forms of the protein, which radically subvert the nature of the p53 pathway by promoting invasion, metastasis and chemoresistance. In this review, we consider available evidence suggesting that mutant p53 proteins can favor cancer cell survival and tumor progression by acting as homeostatic factors that sense and protect cancer cells from transformation-related stress stimuli, including DNA lesions, oxidative and proteotoxic stress, metabolic inbalance, interaction with the tumor microenvironment, and the immune system. These activities of mutant p53 may explain cancer cell addiction to this particular oncogene, and their study may disclose tumor vulnerabilities and synthetic lethalities that could be exploited for hitting tumors bearing missense TP53 mutations

Regulation of Enhancer Elements by p53 in Human Cancer

While the dynamic crosstalk between cancer and immune cells within the tumor microenvironment have been extensively investigated, the mechanisms by which immune signaling drives alterations in the cancer cell transcriptome remain to be fully examined. Notably, cytokines such as TNF-α that are released by immune cells can serve as tumor promoting signals to trigger activation of pro-oncogenic networks by the master inflammatory regulator, NFκB. Importantly, tumor promoting properties of inflammation are further regulated by various genetic aberrations in cancer cells. Of special interest are gain-of-function (GOF) mutations in the tumor suppressor gene, p53 which occur in approximately 50% of all human cancers and have been established to promote inflammation-induced oncogenesis.in this dissertation, I provide mechanistic insights into the various modes by which mutant p53 fuels proinflammatory gene expression programs in colon cancer cells. First, I established that mutant p53 and NFκB redirect each other’s binding to distinct subsets of distal regulatory elements, commonly referred to as enhancers in response to chronic TNF signaling. Notably, this co-occupancy by mutant p53 and NFκB results in activation of such pro-tumorigenic enhancers. I also found that mutant p53 regulates the enhancer occupancy of the RNA polymerase II machinery and supports the biogenesis of nascent transcripts known as enhancer RNAs (eRNAs). Importantly, this pro-inflammatory eRNA signature was dependent on mutant p53 and not detected in cancer cell lines or human nonneoplastic tissues that expressed wild type p53. Our group has since revealed the consequences of mutant p53-dependent eRNAs in gene regulation by establishing that these transcripts form complexes with the bromodomain and extra-terminal motif (BET) protein, BRD4 which often occupies active enhancers and regulates inflammatory and oncogenic programs. In this dissertation, I further explore the significance of transcriptional cofactors also functioning as noncanonical RNA binding proteins by establishing DNA topoisomerase 1 (TOP1) as an RNA interacting factor and demonstrating TOP1’s dependency on RNA associations to maintain its native protein interactome. Collectively, these findings define previously unrecognized mechanisms by which mutant p53 promotes inflammation-induced tumorigenesis through modulation of enhancer activity and underscore critical consequences of RNA-protein complexes

Regulation of Enhancer Elements by p53 in Human Cancer

While the dynamic crosstalk between cancer and immune cells within the tumor microenvironment have been extensively investigated, the mechanisms by which immune signaling drives alterations in the cancer cell transcriptome remain to be fully examined. Notably, cytokines such as TNF-α that are released by immune cells can serve as tumor promoting signals to trigger activation of pro-oncogenic networks by the master inflammatory regulator, NFκB. Importantly, tumor promoting properties of inflammation are further regulated by various genetic aberrations in cancer cells. Of special interest are gain-of-function (GOF) mutations in the tumor suppressor gene, p53 which occur in approximately 50% of all human cancers and have been established to promote inflammation-induced oncogenesis.in this dissertation, I provide mechanistic insights into the various modes by which mutant p53 fuels proinflammatory gene expression programs in colon cancer cells. First, I established that mutant p53 and NFκB redirect each other’s binding to distinct subsets of distal regulatory elements, commonly referred to as enhancers in response to chronic TNF signaling. Notably, this co-occupancy by mutant p53 and NFκB results in activation of such pro-tumorigenic enhancers. I also found that mutant p53 regulates the enhancer occupancy of the RNA polymerase II machinery and supports the biogenesis of nascent transcripts known as enhancer RNAs (eRNAs). Importantly, this pro-inflammatory eRNA signature was dependent on mutant p53 and not detected in cancer cell lines or human nonneoplastic tissues that expressed wild type p53. Our group has since revealed the consequences of mutant p53-dependent eRNAs in gene regulation by establishing that these transcripts form complexes with the bromodomain and extra-terminal motif (BET) protein, BRD4 which often occupies active enhancers and regulates inflammatory and oncogenic programs. In this dissertation, I further explore the significance of transcriptional cofactors also functioning as noncanonical RNA binding proteins by establishing DNA topoisomerase 1 (TOP1) as an RNA interacting factor and demonstrating TOP1’s dependency on RNA associations to maintain its native protein interactome. Collectively, these findings define previously unrecognized mechanisms by which mutant p53 promotes inflammation-induced tumorigenesis through modulation of enhancer activity and underscore critical consequences of RNA-protein complexes