A5101522897- Microtubule and mitosis dynamics
- Cancer-related Molecular Pathways
- Cancer, Hypoxia, and Metabolism
- Cellular Mechanics and Interactions
- Neuroblastoma Research and Treatments
- Force Microscopy Techniques and Applications
- 14-3-3 protein interactions
- Ubiquitin and proteasome pathways
- Cancer Treatment and Pharmacology
- Adhesion, Friction, and Surface Interactions
- Hippo pathway signaling and YAP/TAZ
- Zebrafish Biomedical Research Applications
- Cell Image Analysis Techniques
- Circadian rhythm and melatonin
- Neural dynamics and brain function
- Cancer Cells and Metastasis
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiomyopathy and Myosin Studies
- Ion Transport and Channel Regulation
- Cognitive Science and Education Research
- Neurobiology and Insect Physiology Research
- Ion channel regulation and function
- Neural Networks and Applications
- Heat shock proteins research
- Monoclonal and Polyclonal Antibodies Research
National Center for Advancing Translational Sciences
2019-2023
Stanford University
2011-2023
National Institutes of Health
2019
California Institute of Technology
2019
Mechanotransduction at cell–cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, weak in solution but strengthened applied force due force-dependent transitions between strong actin-binding states. Here, we provide direct evidence from optical trapping...
Therapeutic antibody design is a complex multi-property optimization problem that traditionally relies on expensive search through sequence space. Here, we introduce "Lab-in-the-loop," paradigm shift for orchestrates generative machine learning models, multi-task property predictors, active ranking and selection, in vitro experimentation semi-autonomous, iterative loop. By automating the of variants, prediction, selection designs to assay lab, ingestion data, enable holistic, end-to-end...
Abstract Purpose: Ewing sarcoma is an aggressive solid tumor malignancy of childhood. Although current treatment regimens cure approximately 70% patients with localized disease, they are ineffective for most metastases or relapse. New combinations necessary these patients. Experimental Design: cells dependent on focal adhesion kinase (FAK) growth. To identify candidate sarcoma, we performed a small-molecule library screen to compounds synergistic FAK inhibitors in impairing cell The activity...
Abstract The circadian clock ensures that behavioral and physiological processes occur at appropriate times during the 24-hour day/night cycle, is regulated both cellular organismal levels. To identify pathways acting on intact animals, we performed a small molecule screen using luminescent reporter of molecular rhythms in zebrafish larvae. We identified known novel affect period, amplitude phase. Several drugs did not cultured cells derived from embryos or established mammalian cell lines,...
Members of the Myb oncoprotein and E2F-Rb tumor suppressor protein families are present within same highly conserved multiprotein transcriptional repressor complex, named either as synthetic multivuval class B (Myb-MuvB) or Drosophila Rb E2F Myb-interacting proteins (dREAM). We now report that animal-specific C terminus but not more N-terminal DNA-binding domain is necessary sufficient for ( i ) adult viability, ii proper localization to chromosomes in vivo, iii regulation gene expression iv...
Abstract Mechanotransduction at cell-cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, weak in solution but strengthened applied force due force-dependent transitions between strong actin-binding states. Here, we provide direct evidence from optical trapping...
Abstract Classical cadherins are transmembrane proteins whose extracellular domains link neighboring cells, and intracellular connect to the actin cytoskeleton via β-catenin, α- catenin. The cadherin-catenin complex transmits forces that drive tissue morphogenesis wound healing. In addition, tension-dependent changes in αE-catenin conformation enables it recruit actin-binding protein vinculin cell-cell junctions, where contributes junctional strengthening. How whether multiple...
<p>Supplemental Table S3. Target sequences for shRNAs targeting AURKB expression in the vivo dependency screen</p>
<p>Supplemental Table S6. Muliple metrics were used to calculate synergy of all compounds tested from MIPE 4.0 library in combination with PF-562271. Highlighted green are Pan-Aurora Inhibitors, red Aurora B inhibitors, and blue A inhibitors.</p>
<p>Supplemental Table S4. Target sequences for sgRNA guides targeting AURKB, AURKA, and FAK genes</p>
<p>Supplemental Table S7. Reverse Phase Protein Array (RPPA) data. Total protein and phosphorylation levels in untreated treated A673 TC32 cells are normalized to total each sample.</p>
<p>Supplemental Table S5. Target sequences for shRNAs targeting AURKB and EWS/FLI expression</p>
<p>Supplemental Table S2. Target sequences for shRNAs targeting AURKB expression in the Achilles Project</p>
<p>Supplemental Table S1. List of compounds in MIPE 4.0 compound library</p>
<p>Supplemental Table S1. List of compounds in MIPE 4.0 compound library</p>
<p>Supplemental Table S6. Muliple metrics were used to calculate synergy of all compounds tested from MIPE 4.0 library in combination with PF-562271. Highlighted green are Pan-Aurora Inhibitors, red Aurora B inhibitors, and blue A inhibitors.</p>
<p>Supplemental Table S2. Target sequences for shRNAs targeting AURKB expression in the Achilles Project</p>
<p>Supplemental Methods and Figures Supplemental Figure S1. Aurora kinase expression in Ewing sarcoma S2. Effects of cell growth on response to AZD-1152 as a function duration treatment. S3. FAK inhibitor combinations are synergistic lines S4. Response treated with inhibitors S5. Cell cycle apoptotic effects B knock out S6. PYK2 is poorly expressed cells S7. Zebrafish Murine studies</p>
<p>Supplemental Table S3. Target sequences for shRNAs targeting AURKB expression in the vivo dependency screen</p>
<p>Supplemental Table S4. Target sequences for sgRNA guides targeting AURKB, AURKA, and FAK genes</p>
<p>Supplemental Table S7. Reverse Phase Protein Array (RPPA) data. Total protein and phosphorylation levels in untreated treated A673 TC32 cells are normalized to total each sample.</p>
<p>Supplemental Table S5. Target sequences for shRNAs targeting AURKB and EWS/FLI expression</p>
<div>AbstractPurpose:<p>Ewing sarcoma is an aggressive solid tumor malignancy of childhood. Although current treatment regimens cure approximately 70% patients with localized disease, they are ineffective for most metastases or relapse. New combinations necessary these patients.</p>Experimental Design:<p>Ewing cells dependent on focal adhesion kinase (FAK) growth. To identify candidate Ewing sarcoma, we performed a small-molecule library screen to compounds...