A5063398311- RNA modifications and cancer
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- Computational Drug Discovery Methods
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Cancer-related gene regulation
- Advanced biosensing and bioanalysis techniques
- RNA regulation and disease
- Single-cell and spatial transcriptomics
- interferon and immune responses
- Cancer Genomics and Diagnostics
- Cell Image Analysis Techniques
Columbia University
2022-2025
Columbia University Irving Medical Center
2022-2025
University of California, San Francisco
2018-2024
UCSF Helen Diller Family Comprehensive Cancer Center
2019-2024
Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19 (refs. 1,2). However, because SARS-CoV-2 evolved become resistant other therapeutic modalities3-9, there is a concern that same could occur for nirmatrelvir. Here we examined this possibility by in vitro passaging nirmatrelvir using two independent approaches, including one on large scale. Indeed, highly viruses emerged from both and their sequences showed...
Post-transcriptional regulation of RNA stability is a key step in gene expression control. We describe regulatory program, mediated by the binding protein TARBP2, that controls nucleus. TARBP2 to pre-mRNAs results increased intron retention, subsequently leading targeted degradation TARBP2-bound transcripts. This recruitment m6A methylation machinery its target transcripts, where deposition marks influences splicing regulators, inhibiting efficient splicing. Interactions between and...
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...
Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful in reducing hospitalization or death due COVID-19 1,2 . However, as SARS-CoV-2 evolved become resistant other therapeutic modalities 3â€"9 , there is a concern that same could occur for nirmatrelvir. Here, we have examined this possibility by vitro passaging increasing concentrations nirmatrelvir using two independent approaches, including one on large scale 480 wells....
Loss of RNA homeostasis underlies numerous neurodegenerative and neuroinflammatory diseases. However, the molecular mechanisms that trigger neuroinflammation are poorly understood. Viral double-stranded (dsRNA) triggers innate immune responses when sensed by host pattern recognition receptors (PRRs) present in all cell types. Here, we report human neurons intrinsically carry exceptionally high levels immunostimulatory dsRNAs identify long 3'UTRs as giving rise to neuronal dsRNA structures....
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...
Dysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable mature, healthy (CNS). Neurons have generally been considered incapable antigen presentation, although interferon gamma (IFN-γ) can elicit neuronal MHC class I (MHC-I) expression presentation vitro, it has unclear whether similar...
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) as the etiologic agent of COVID-19 (coronavirus disease 2019) has drastically altered life globally. Numerous efforts have been placed on development therapeutics to treat infection. One particular target is 3CL protease (3CL pro ), which holds promise it essential virus and highly conserved among coronaviruses, suggesting that may be possible find broad inhibitors not just but other infections well. While studied by many groups...
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...
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...
Abstract Broad dysregulation of gene expression control is a hallmark cancer progression. Identifying the underlying master regulators that drive pathological key challenge in precision oncology. Here, we have developed network analytical framework, named PRADA, identifies oncogenic RNA-binding proteins through systematic detection coordinated changes their target regulons. Application this approach to data collected from clinical samples, patient-derived xenografts, and cell line models...
Abstract Background: Breast cancer progression accompanies broad reprogramming of the alternative splicing landscape with functional implications for tumor growth and metastasis. However, underlying regulatory pathways that are hijacked by cells to drive pathological programs remain largely unknown. Here, we have described a novel pathway, mediated factor SNRPA1, promotes breast progression. Results: We used high-coverage RNA sequencing compare patterns in highly metastatic (MDA-LM2) their...
Abstract Dysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable mature, healthy (CNS). Neurons have generally been considered incapable antigen presentation, although interferon gamma (IFN-γ) can elicit neuronal MHC class I (MHC-I) expression presentation vitro , it remains unclear whether...
Abstract Background: Metabolic reprogramming is a hallmark of breast cancer progression. However, the underlying regulatory pathways that initiate and maintain this process remain largely unexplored. Recently, we have identified novel antisense RNA helps protect cells against oxidative stress by their metabolic redox state. Using cell line patient-derived xenograft models, as well direct measurements in clinical samples, demonstrated unique functions increasing metastatic capacity cells....
Abstract Antisense RNAs are ubiquitous in human cells, yet the role that they play healthy and diseased states remains largely unexplored. Here, we developed a computational framework to catalog profile antisense applied it poorly highly metastatic breast cancer cell lines. We identified one RNA plays functional driving progression by upregulating redox enzyme NQO1, hence named NQO1-antisense or NQO1-AS. This upregulation occurs via stabilizing interaction between NQO1-AS its complementary...
Abstract Antisense RNAs are ubiquitous in human cells, yet the role that they play healthy and diseased states remains largely unexplored. Here, we developed a computational framework to catalog profile antisense applied it poorly highly metastatic breast cancer cell lines. We identified one RNA plays functional driving progression by upregulating redox enzyme NQO1, hence named NQO1-antisense or NQO1-AS. This upregulation occurs via stabilizing interaction between NQO1-AS its complementary...