Biology subjects

Rivera, K.

Publications and source records attributed to Rivera, K..

6 recordsLinked to original sources

bioRxiv2026

Defining Quality Control Standards for Single-Cell Proteomics by Inter-Laboratory Benchmarking

Single-cell proteomics can quantify thousands of proteins from individual mammalian cells, yet the absence of community-wide quality control limits biological interpretability. Here, the HUPO Single Cell Initiative presents the first inter-laboratory single-cell proteomics benchmarking study across seven laboratories using standardized 384-well plates acquired on Orbitrap Astral and timsTOF Ultra2 instruments. Centralized analysis across six DIA software tools revealed that software choice impacts identification depth and quantitative accuracy more than instrument vendor. Multi-layered quality control enabled the detection of cell-leakage during sorting, LC misconfiguration, column degradation and site-specific pipetting failures. Inter-lab quantitative correlations were strongest between instruments of the same vendor relative to cross-platform comparisons. Sequential correction for plate identity and well position recovered clean cell-type separation for confident downstream differential expression analysis. This study provides a data-driven quality control framework spanning plate design to batch correction for reproducible single-cell proteomics across laboratories and platforms.

biochemistry↗

bioRxiv2025

A phenotypic screen identified KEAP1-kelch domain blockade as a mechanism to restore cardiac function in the setting of chronic severe hemodynamic stress

A bespoke gene expression (GE) based small molecule screen in human induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) was conducted with the aim of identifying drug targets and pathways with the potential to reverse heart failure (HF) pathologic GE and the resultant decompensated HF phenotype. The screen utilized a composite human-murine HF gene expression signature, a target annotated compound set, and a HF gene expression reversal scoring algorithm to identify small molecules and their associated targets as potential modulators of HF pathologic GE. Following hit triage, a lead optimization program, and compound characterization in preclinical rodent models of HF and human iPSC-CM contractility assays, KEAP1 kelch domain blockers were identified as potent efficacious agents in the restoration of contractile function in the setting of oxidant stress and pressure overload induced cardiac dysfunction.

molecular biology↗

bioRxiv2021

Prostate tumor-induced stromal reprogramming generates Tenascin C that promotes prostate cancer metastasis through YAP/TAZ inhibition

Metastatic prostate cancer (PCa) in bone induces bone-forming lesions that enhance PCa progression. How tumor-induced bone formation enhances PCa progression is not known. We have previously shown that PCa-induced bone originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition by tumor-secreted BMP4. Here, we show that EC-to-OSB transition leads to changes in the tumor microenvironment that increases the metastatic potential of PCa cells. We found that conditioned medium (CM) from EC-OSB hybrid cells increases the migration, invasion and survival of PC3-mm2 and C4-2B4 PCa cells. Quantitative mass spectrometry (iTRAQ) identified Tenascin C (TNC) as one of the major proteins secreted from EC-OSB hybrid cells. TNC expression in tumor-induced osteoblasts was confirmed by immunohistochemistry of MDA-PCa118b xenograft and human bone metastasis specimens. Mechanistically, BMP4 increases TNC expression in EC-OSB cells through the Smad1-Notch/Hey1 pathway. How TNC promotes PCa metastasis was next interrogated by in vitro and in vivo studies. In vitro studies showed that a TNC neutralizing antibody inhibits EC-OSB-CM-mediated PCa cell migration and survival. TNC knockdown decreased, while addition of recombinant TNC or TNC overexpression increased migration and anchorage-independent growth of PC3 or C4-2b cells. When injected orthotopically, PC3-mm2-shTNC clones decreased metastasis to bone, while C4-2b-TNC overexpressing cells increased metastasis to lymph nodes. TNC enhances PCa cell migration through 5{beta}1 integrin-mediated YAP/TAZ inhibition. These studies elucidate that tumor-induced stromal reprogramming generates TNC that enhances PCa metastasis and suggest that TNC may be a target for PCa therapy.

cancer biology↗

bioRxiv2021

Rethinking habitat occupancy modeling and the role of diel activity in an anthropogenic world

Current methods to model species habitat use through space and diel time are limited. Development of such models is critical when considering rapidly changing habitats where species are forced to adapt to anthropogenic change, often by shifting their diel activity across space. We use an occupancy modeling framework to develop a new model, the multi-state diel occupancy model (MSDOM), which can evaluate species diel activity against continuous response variables which may impact diel activity within and across seasons or years. We used two case studies, fosa in Madagascar and coyote in Chicago, USA, to conceptualize the application of this model and to quantify the impacts of human activity on species spatial use in diel time. We found support that both species varied their habitat use by diel states--in and across years, and by human disturbance. Our results exemplify the importance of understanding animal diel activity patterns and how human disturbance can lead to temporal habitat loss. The MSDOM will allow more focused attention in ecology and evolution studies on the importance of the short temporal scale of diel time in animal-habitat relationships and lead to improved habitat conservation and management.

ecology↗

bioRxiv2021

PHAROH lncRNA regulates c-Myc translation in hepatocellular carcinoma via sequestering TIAR

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a c-Myc motif in their promoter. C-MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases c-MYC translation. In summary, our data suggest that PHAROH regulates c-MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma.

cancer biology↗

bioRxiv2020

Noisy Pooled PCR for Virus Testing

Fast testing can help mitigate the coronavirus disease 2019 (COVID-19) pandemic. Despite their accuracy for single sample analysis, infectious diseases diagnostic tools, like RT-PCR, require substantial resources to test large populations. We develop a scalable approach for determining the viral status of pooled patient samples. Our approach converts group testing to a linear inverse problem, where false positives and negatives are interpreted as generated by a noisy communication channel, and a message passing algorithm estimates the illness status of patients. Numerical results reveal that our approach estimates patient illness using fewer pooled measurements than existing noisy group testing algorithms. Our approach can easily be extended to various applications, including where false negatives must be minimized. Finally, in a Utopian world we would have collaborated with RT-PCR experts; it is difficult to form such connections during a pandemic. We welcome new collaborators to reach out and help improve this work!

molecular biology↗