A5066016635- Microtubule and mitosis dynamics
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Hippo pathway signaling and YAP/TAZ
- Cellular transport and secretion
- Fibroblast Growth Factor Research
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Cancer-related gene regulation
- Photosynthetic Processes and Mechanisms
- Cancer Cells and Metastasis
- IL-33, ST2, and ILC Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Autophagy in Disease and Therapy
- Fungal and yeast genetics research
- Genetic Associations and Epidemiology
- Gene expression and cancer classification
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Cytokine Signaling Pathways and Interactions
- Phagocytosis and Immune Regulation
- Extracellular vesicles in disease
University of California, San Francisco
2021-2024
University of California, Irvine
2017
Cancers have been associated with a diverse array of genomic alterations. To help mechanistically understand such alterations in breast-invasive carcinoma, we applied affinity purification–mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer (BC) proteins, and without relevant mutations, across three human cell lines. These identify cancer-specific protein-protein interactions (PPIs), interconnected enriched common rare that...
Abstract Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell (NSCLC) subtypes with oncogenic alterations EGFR, ALK and KRAS. The success limited by drug-tolerant persister cells (DTPs) which withstand adapt to treatment comprise residual disease state that typical during clinical therapies. Here, we integrate studies patient-derived immunocompetent...
A major goal of cancer research is to understand how mutations distributed across diverse genes affect common cellular systems, including multiprotein complexes and assemblies. Two challenges—how comprehensively map such systems identify which are under mutational selection—have hindered this understanding. Accordingly, we created a comprehensive protein integrating both new published multi-omic interaction data at multiple scales analysis. We then developed unified statistical model that...
We outline a framework for elucidating tumor genetic complexity through multidimensional protein-protein interaction maps and apply it to enhancing our understanding of head neck squamous cell carcinoma. This network uncovers 771 interactions from cancer noncancerous states, including WT mutant protein isoforms. Prioritization cancer-enriched reveals previously unidentified association the fibroblast growth factor receptor tyrosine kinase 3 with Daple, guanine-nucleotide exchange factor,...
Astrocytes respond and contribute to neuroinflammation by adopting inflammatory reactive states. Although recent efforts have characterized the gene expression signatures associated with these states, cell biology underlying astrocyte phenotypes remains under-explored. Here, we used CRISPR-based screening in human iPSC-derived astrocytes identify mTOR activation a driver of cytokine-induced endolysosomal system remodeling, manifesting as alkalinization compartments, decreased autophagic...
The ability of the small GTPase Cdc42 to regulate diverse cellular processes depends on tight spatial control its activity. function is best understood at plasma membrane (PM), where it regulates cytoskeletal organization and cell polarization. Active has also been detected Golgi, but role regulation this organelle are only partially understood. Here we analyze distribution activity by moni-toring dynamics FLARE biosensor using phasor approach FLIM-FRET. Phasor analysis revealed that active...
Abstract Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell (NSCLC) subtypes with oncogenic alterations EGFR, ALK and KRAS. The success limited by drug-tolerant cells which withstand adapt to treatment comprise residual disease state that typical during clinical therapies. Here, we integrate studies patient-derived immunocompetent models specimens...
ABSTRACT Astrocytes respond and contribute to neuroinflammation by adopting inflammatory reactive states. Although recent efforts have characterized the gene expression signatures associated with these states, cell biology underlying astrocyte phenotypes remains under-explored. Here, we used CRISPR-based screening in human iPSC-derived astrocytes identify mTOR activation a driver of cytokine-induced endolysosomal system remodeling, manifesting as alkalinization compartments, decreased...
Abstract While KRAS is among the most frequently mutated oncogenes, our understanding of mechanisms KRAS-driven oncogenesis remains limited. A significant remaining gap a lack tissue-specific effectors Ras activation and role specific mutations in determining downstream vulnerabilities. Previously, we used combination proteomics CRISPR/Cas9 screens human lung adenocarcinoma (LUAD) cells to identify KRAS-specific vulnerability induced by combined loss RHOA long isoform RAP1GDS1, suggesting...
Abstract While KRAS is among the most frequently mutated oncogenes, our understanding of mechanisms KRAS-driven oncogenesis remains limited. A significant remaining gap a lack tissue-specific effectors Ras activation and role specific mutations in determining downstream vulnerabilities. Previously, we used combination proteomics CRISPR/Cas9 screens human lung adenocarcinoma (LUAD) cells to identify KRAS-specific vulnerability induced by combined loss RHOA long isoform RAP1GDS1, suggesting...