A5008943388- Hippo pathway signaling and YAP/TAZ
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- Sarcoma Diagnosis and Treatment
- Histone Deacetylase Inhibitors Research
- Integrated Circuits and Semiconductor Failure Analysis
- Protein Degradation and Inhibitors
- ATP Synthase and ATPases Research
- CAR-T cell therapy research
- Virus-based gene therapy research
- Advanced MRI Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Cell Image Analysis Techniques
- Lanthanide and Transition Metal Complexes
- Cancer-related gene regulation
- Pancreatic function and diabetes
- Biochemical and Molecular Research
- Metabolomics and Mass Spectrometry Studies
- Neutropenia and Cancer Infections
- Epigenetics and DNA Methylation
- Click Chemistry and Applications
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
Salk Institute for Biological Studies
2020-2023
National Cancer Institute
2016-2020
Center for Cancer Research
2020
National Institutes of Health
2016-2019
Molecular Oncology (United States)
2017
Oregon Health & Science University
2016
Czech Academy of Sciences, Institute of Microbiology
1988
Parkin is phosphorylated on Ser 108 in ACT domain by AMPK/ULK1 signaling within minutes of mitochondrial stress.
Altered cellular metabolism, including an increased dependence on aerobic glycolysis, is a hallmark of cancer. Despite the fact that this observation was first made nearly century ago, effective therapeutic targeting glycolysis in cancer has remained elusive. One potentially promising approach involves glycolytic enzyme lactate dehydrogenase (LDH), which overexpressed and plays critical role several cancers. Here, we used novel class LDH inhibitors to demonstrate, for time, Ewing sarcoma...
Adeno-associated virus (AAV) vectors have made great progress in their use for gene therapy; however, fundamental aspects of AAV's capsid assembly remain poorly characterized. In this regard, the discovery assembly-activating protein (AAP) sheds new light on crucial part AAV biology and vector production. Previous studies shown that AAP is essential assembly; how its mechanistic roles might differ among serotypes remains uncharacterized. Here, we show biological properties AAPs processes are...
HDAC3 is one of the main targets histone deacetylase (HDAC) inhibitors in clinical development as cancer therapies, yet vivo role solid tumors unknown. We identified a critical for Kras -mutant lung cancer. Using genetically engineered mouse models (GEMMs), we found that required tumor growth vivo. was to direct and enhance transcription effects lineage factor NKX2-1 mediate expression common set target genes. FGFR1 previously unidentified HDAC3. Leveraging this, an HDAC3-dependent...
Purpose: Although many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored in vitro response of sarcoma cell lines against a large collection investigational and approved drugs identify candidate combinations.Experimental Design: Drugs displaying activity as single agents were evaluated combinatorial (matrix) format highly active, synergistic drug combinations,...
Long-term survival in patients with metastatic, relapsed, or recurrent Ewing sarcoma and rhabdomyosarcoma is dismal. Irinotecan, a topoisomerase 1 inhibitor, has activity these sarcomas, but due to poor bioavailability of its active metabolite (SN-38) had limited clinical efficacy. In this study we have evaluated the efficacy toxicity STA-8666, novel drug conjugate which uses an HSP90 inhibitor facilitate intracellular, tumor-targeted delivery SN-38, thus preferentially delivering...
Rhabdomyosarcoma is the most common childhood soft-tissue sarcoma, yet patients with metastatic or recurrent disease continue to do poorly, indicating a need for new treatments. The SRC family tyrosine kinase YES1 upregulated in rhabdomyosarcoma and necessary growth, but clinical trials using single agent dasatinib, inhibitor, have failed sarcomas. YAP1 (YES-associated protein) highly expressed rhabdomyosarcoma, driving growth survival when upstream Hippo tumor suppressor pathway silenced,...
To determine what alternative pathways may act as mechanisms of bypass resistance to type 1 insulin-like growth factor receptor (IGF-1R) blockade in rhabdomyosarcoma (RMS), we compared expression tyrosine kinase activity a number IGF-1R antibody-resistant and -sensitive RMS cell lines. We found that platelet-derived β (PDGFR-β) was upregulated three xenograft-derived lines arose from highly sensitive fusion-positive line (Rh41). Furthermore, identified four additional fusion-negative...
Summary Transcriptional deregulation is a common feature of many cancers, which often accompanied by changes in epigenetic controls. These findings have led to the development therapeutic agents aimed at broad modulation and reprogramming transcription variety cancers. Histone Deacetylase 3, HDAC3, one main targets HDAC inhibitors currently clinical as cancer therapies, yet vivo role HDAC3 solid tumors unknown. Here, we define two genetic engineered models most subtypes Kras-driven Non-Small...
11022 Background: PARPi have emerged as an intriguing new treatment strategy for patients with ES. However, single agent activity of in preclinical vivo models and early phase clinical trials ES failed to demonstrate meaningful responses, necessitating the use rational combinations. PARP enzymes mediate DNA repair and, importantly, utilize NAD a necessary substrate. Thus far, combination studies focused on damaging agents anticipation enhanced efficacy, but been limited by toxicity. In this...
<div>Abstract<p>Rhabdomyosarcoma is the most common childhood soft-tissue sarcoma, yet patients with metastatic or recurrent disease continue to do poorly, indicating a need for new treatments. The SRC family tyrosine kinase YES1 upregulated in rhabdomyosarcoma and necessary growth, but clinical trials using single agent dasatinib, inhibitor, have failed sarcomas. YAP1 (YES-associated protein) highly expressed rhabdomyosarcoma, driving growth survival when upstream Hippo tumor...
<div>Abstract<p>Altered cellular metabolism, including an increased dependence on aerobic glycolysis, is a hallmark of cancer. Despite the fact that this observation was first made nearly century ago, effective therapeutic targeting glycolysis in cancer has remained elusive. One potentially promising approach involves glycolytic enzyme lactate dehydrogenase (LDH), which overexpressed and plays critical role several cancers. Here, we used novel class LDH inhibitors to demonstrate,...
<p>Metabolic outcomes</p>
<p>Metabolic outcomes</p>
<p>Proteomic outcomes</p>
<div>Abstract<p><b>Purpose:</b> Although many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored <i>in vitro</i> response of sarcoma cell lines against a large collection investigational and approved drugs identify candidate combinations.</p><p><b>Experimental Design:</b> Drugs displaying activity as...
<div>Abstract<p><b>Purpose:</b> Although many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored <i>in vitro</i> response of sarcoma cell lines against a large collection investigational and approved drugs identify candidate combinations.</p><p><b>Experimental Design:</b> Drugs displaying activity as...
<p>Supplementary Methods and Supplementary Figures</p>
<p>Single-agent outcomes</p>
<p>Supplementary Methods and Supplementary Figures</p>