A5050122991- Vascular Tumors and Angiosarcomas
- Acute Myeloid Leukemia Research
- Renal and related cancers
- Hippo pathway signaling and YAP/TAZ
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- Microtubule and mitosis dynamics
- Cancer Cells and Metastasis
- Marine Biology and Environmental Chemistry
- Kruppel-like factors research
- Connective Tissue Growth Factor Research
- Chronic Myeloid Leukemia Treatments
- Wnt/β-catenin signaling in development and cancer
- Glioma Diagnosis and Treatment
- Silk-based biomaterials and applications
- Plant Surface Properties and Treatments
- Hedgehog Signaling Pathway Studies
- Skin and Cellular Biology Research
- Neurobiology and Insect Physiology Research
- Multiple Myeloma Research and Treatments
Cleveland Clinic
2022-2024
Cleveland Clinic Lerner College of Medicine
2013-2022
Cerner (United States)
2019
Migrating cells need to overcome physical constraints from the local microenvironment navigate their way through tissues. Cells that move collectively have additional challenge of negotiating complex environments in vivo while maintaining cohesion group as a whole. The mechanisms by which collectives maintain migratory morphology resisting surrounding tissue are poorly understood. Drosophila border represent genetic model collective migration within cell-dense tissue. Border cohesive 6-10...
Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma caused by the WWTR1(TAZ)-CAMTA1 (TC) gene fusion. This fusion has been observed in almost all reported EHE cases and functions as constitutively activated TAZ. Sequencing of human tumors has, however, identified additional secondary mutations approximately 50% EHE, most commonly loss tumor suppressor CDKN2A. In this study, effect CDKN2A tumorigenesis was evaluated.Mice bearing conditional TC allele were paired with Cdkn2a knockout...
Abstract Purpose: A consistent genetic alteration in vascular cancer epithelioid hemangioendothelioma (EHE) is the t(1;3)(p36;q25) chromosomal translocation, which generates a WWTR1(TAZ)-CAMTA1 (TC) fusion gene. TC transcriptional coactivator that drives EHE. Here, we aimed to identify targets and signaling mechanisms underlie EHE tumorigenesis. Experimental Design: We used NIH3T3 cells transformed with (NIH3T3/TC) as model system uncover TC-dependent oncogenic signaling. These proliferated...
Glioblastoma (GBM) is the most prevalent primary malignant brain tumor and associated with extensive cell infiltration into adjacent parenchyma. However, there are limited targeted therapies that address this disease hallmark. While invasive capacity of self-renewing cancer stem cells (CSCs) their non-CSC progeny has been investigated, mode(s) migration used by CSCs during invasion currently unknown. Here we time-lapse microscopy to evaluate migratory behavior CSCs, a focus on identifying...
Collective cell migration is central to many developmental and pathological processes. However, the mechanisms that keep collectives together coordinate movement of multiple cells are poorly understood. Using Drosophila border model, we find Protein phosphatase 1 (Pp1) activity controls collective cohesion migration. Inhibition Pp1 causes round up, dissociate, move as single with altered motility. We present evidence promotes proper levels cadherin-catenin complex proteins at cell-cell...
Starting from our previously reported hit, a series of 1,5-diaryl-1,2,3-triazole-4-carbohydrazones were synthesized and evaluated as inhibitors the YAP/TAZ-TEAD complex. Their binding to hTEAD2 was confirmed by nanodifferential scanning fluorimetry, some compounds also found moderately disrupt YAP-TEAD interaction, assessed fluorescence polarization assay. A TEAD luciferase gene reporter assay performed in HEK293T cells RTqPCR measurements MDA-MB231 showed that these inhibit activity...
There are no effective treatment options for patients with aggressive epithelioid hemangioendothelioma (EHE) driven by the TAZ-CAMTA1 (TC) fusion gene. Here, we aimed to understand regulation of TC using pharmacologic tools and identify vulnerabilities that can potentially be exploited EHE.
Cell motility is essential for embryonic development and physiological processes such as the immune response, but also contributes to pathological conditions tumor progression inflammation. However, our understanding of mechanisms underlying migratory incomplete. Drosophila border cells provide a powerful genetic model identify roles genes that contribute cell migration.Members Hedgehog signaling pathway were uncovered in two independent screens interactions with small GTPase Rac polarity...
Disrupting the formation of oncogenic YAP/TAZ-TEAD transcriptional complex holds substantial therapeutic potential. However, three protein interaction interfaces this cannot be easily disrupted using small molecules. Here, we report that pharmacologically active molecule aurintricarboxylic acid (ATA) acts as a disruptor TAZ-TEAD complex. ATA was identified in high-throughput screen AlphaLISA assay tailored to identify disruptors We further used fluorescence polarization assays both confirm...
<div>AbstractPurpose:<p>There are no effective treatment options for patients with aggressive epithelioid hemangioendothelioma (EHE) driven by the <i>TAZ–CAMTA1</i> (<i>TC</i>) fusion gene. Here, we aimed to understand regulation of TC using pharmacologic tools and identify vulnerabilities that can potentially be exploited EHE.</p>Experimental Design:<p>TC is a transcriptional coregulator; hypothesized compounds reduce nuclear levels, either...
<p>Figure S1. Dose-response curves of triptonide, triptolide, and dBET6</p>
<p>Figure S2. Localization of TC following Dina + MG132 treatment</p>
<p>Figure S2. Localization of TC following Dina + MG132 treatment</p>
<p>Figure S1. Dose-response curves of triptonide, triptolide, and dBET6</p>
<div>AbstractPurpose:<p>There are no effective treatment options for patients with aggressive epithelioid hemangioendothelioma (EHE) driven by the <i>TAZ–CAMTA1</i> (<i>TC</i>) fusion gene. Here, we aimed to understand regulation of TC using pharmacologic tools and identify vulnerabilities that can potentially be exploited EHE.</p>Experimental Design:<p>TC is a transcriptional coregulator; hypothesized compounds reduce nuclear levels, either...
<div>AbstractPurpose:<p>Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma caused by the <i>WWTR1(TAZ)</i>–<i>CAMTA1</i> (TC) gene fusion. This fusion has been observed in almost all reported EHE cases and functions as constitutively activated TAZ. Sequencing of human tumors has, however, identified additional secondary mutations approximately 50% EHE, most commonly loss tumor suppressor <i>CDKN2A</i>. In this study, effect...
Abstract Glioblastoma (GBM) is the most prevalent primary malignant brain tumor and associated with extensive cell infiltration into adjacent parenchyma. However, there are limited targeted therapies that address this disease hallmark. While invasive capacity of self-renewing cancer stem cells (CSCs) their non-CSC progeny has been investigated, mode(s) migration used by CSCs during invasion currently unknown. Here we time-lapse microscopy to evaluate migratory behavior CSCs, a focus on...
<p>Gross and microscopic pathology of lymphoma samples</p>
<p>Ki67 staining and single-cell RNA sequencing</p>
<p>Immunohistochemistry of EHE allograft tumors</p>