A5065200410- RNA modifications and cancer
- Cancer Research and Treatments
- Cancer-related gene regulation
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Radiomics and Machine Learning in Medical Imaging
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Biomedical Text Mining and Ontologies
- Pluripotent Stem Cells Research
- Scientific Computing and Data Management
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Machine Learning in Bioinformatics
- Cell Image Analysis Techniques
- Pharmacological Effects of Natural Compounds
- Ferroptosis and cancer prognosis
- ATP Synthase and ATPases Research
- RNA regulation and disease
University of California, San Francisco
2020-2024
UCSF Helen Diller Family Comprehensive Cancer Center
2020-2024
Stanford Medicine
2023-2024
University of California System
2022-2023
Universidad Católica de Santa Fe
2022
Baylor University
2018
Translational Genomics Research Institute
2018
Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report systematic effort to decipher RNA structural code shapes pathological during breast cancer metastasis. We discovered previously unknown enhancer enriched near cassette exons with increased inclusion in highly metastatic cells. show spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts these enhancers...
Abstract Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, address this, we used ribosome profiling compare genome-wide translation efficiencies and highly metastatic breast patient-derived xenografts. We developed dedicated regression-based methods analyse alternative...
Abstract Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one RNA that drives progression by upregulating redox enzyme NADPH quinone dehydrogenase 1 (NQO1), named it NQO1-AS. Knockdown of either NQO1 or NQO1-AS reduced colonization a mouse model, investigation into indicated broadly protective against oxidative damage ferroptosis....
Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes their target regulons. Application this approach to data collected from clinical samples, patient-derived xenografts, and cell line models colon cancer metastasis revealed protein RBMS1 as suppressor progression. We observed...
MicroRNAs are recognized as key drivers in many cancers but targeting them with small molecules remains a challenge. We present RiboStrike, deep-learning framework that identifies against specific microRNAs. To demonstrate its capabilities, we applied it to microRNA-21 (miR-21), known driver of breast cancer. ensure selectivity toward miR-21, performed counter-screens miR-122 and DICER. Auxiliary models were used evaluate toxicity rank the candidates. Learning from various datasets, screened...
Abstract From extrachromosomal DNA to neo-peptides, the broad reprogramming of cancer genome leads emergence molecules that are specific state. We recently described orphan non-coding RNAs (oncRNAs) as a class cancer-specific small with potential play functional roles in breast progression 1 . Here, we report systematic and comprehensive search identify, annotate, characterize cancer-emergent oncRNAs across 32 tumor types. also leverage large-scale vivo genetic screens xenografted mice...
Abstract GI toxicity is a common dose-limiting adverse effect of platin chemotherapy treatment. Up to 50% cancer survivors continue experience symptoms chronic constipation or diarrhea induced by their for many years after This drug largely attributed damage enteric neurons that innervate the tract and control motility. The mechanisms responsible platin-induced neurotoxicity potential preventative strategies have remained unknown. Here, we use human pluripotent stem cell derived establish...
Abstract Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major hub in oncogenesis, however its effects on cancer progression remain poorly understood. To address this, we used ribosome profiling compare genome-wide translation efficiencies and highly metastatic breast patient-derived xenografts. We developed novel regression-based methods analyze alternative...
Summary/Abstract The neural crest (NC) is highly multipotent and generates diverse lineages in the developing embryo. However, spatiotemporally distinct NC populations display differences fate potential, such as increased gliogenic parasympathetic potential from later migrating, nerve-associated Schwann cell precursors (SCPs). Interestingly, while melanogenic shared by both early migrating SCPs, melanocyte identity resulting differentiation through these temporally progenitors have not been...
Abstract Patient-derived cells hold great promise for precision medicine approaches in human health. Human dermal fibroblasts have been a major source of reprogramming and differentiating into specific cell types disease modeling. Postmortem dura mater has suggested as primary vitro modeling neurodegenerative diseases. Although fibroblast-like from mouse previously described, their utility direct differentiation protocols not fully established. In this study, derived postmortem are directly...
Abstract Many agents that show promise in preclinical cancer models lack efficacy patients due to patient heterogeneity is not captured traditional assays. To address this problem, we have developed GENEVA, a platform measures the molecular and phenotypic consequences of drug perturbations within diverse populations cells at single-cell resolution, both vitro vivo . Here, apply GENEVA study KRAS G12C inhibitors, recapitulating known properties these drugs uncovering previously unknown role...
MicroRNAs are recognized as key drivers in many cancers, but targeting them with small molecules remains a challenge. We present RiboStrike, deep learning framework that identifies against specific microRNAs. To demonstrate its capabilities, we applied it to microRNA-21 (miR-21), known driver of breast cancer. ensure the selected only targeted miR-21 and not other microRNAs, also performed counter-screen DICER, an enzyme involved microRNA biogenesis. Additionally, used auxiliary models...
Abstract Large-scale sequencing efforts of thousands tumor samples have been undertaken to understand the mutational landscape coding genome. However, vast majority germline and somatic variants occur within non-coding portions These genomic regions do not directly encode for specific proteins, but can play key roles in cancer progression, example by driving aberrant gene expression control. Here, we designed an integrative computational experimental framework identify recurrently mutated...
ABSTRACT In our cells, a limited number of RNA binding proteins (RBPs) are responsible for all aspects metabolism across the entire transcriptome. To accomplish this, RBPs form regulatory units that act on specific target regulons. However, landscape RBP combinatorial interactions remains poorly explored. Here, we performed systematic annotation via multimodal data integration. We built large-scale map protein neighborhoods by generating in vivo proximity-dependent biotinylation datasets 50...
<div>Abstract<p>Identifying master regulators that drive pathologic gene expression is a key challenge in precision oncology. Here, we have developed an analytic framework, named PRADA, identifies oncogenic RNA-binding proteins through the systematic detection of coordinated changes their target regulons. Application this approach to data collected from clinical samples, patient-derived xenografts, and cell line models colon cancer metastasis revealed protein RBMS1 as suppressor...
<p>Supplementary Figure 7</p>
<p>RBMS1 putative regulons, RBMS1 target list, 80-gene signature list</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure 6</p>