A5024363169- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Plant Molecular Biology Research
- Plant Reproductive Biology
- Histone Deacetylase Inhibitors Research
- Chromatin Remodeling and Cancer
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Plant Parasitism and Resistance
- CRISPR and Genetic Engineering
- Sarcoma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Plant tissue culture and regeneration
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Plant and animal studies
- Plant nutrient uptake and metabolism
- Gender Roles and Identity Studies
- Plant Stress Responses and Tolerance
- Obstructive Sleep Apnea Research
- Legume Nitrogen Fixing Symbiosis
- Menstrual Health and Disorders
- Cancer Genomics and Diagnostics
University Children's Hospital Zurich
2019-2023
University of California, Davis
2007-2021
Children's Clinical University Hospital
2020
Uniwersytecki Szpital Dziecięcy
2020
Pham Ngoc Thach Hospital
2019
University of Lausanne
2018
University of Zurich
2012-2014
University of Peradeniya
2011
Pennsylvania State University
2011
Chicago Botanic Garden
2011
The plant life cycle involves an alternation of generations between sporophyte and gametophyte. Currently, the genes pathways involved in gametophytic development function flowering plants remain largely unknown. A large-scale mutant screen Ds transposon insertion lines was employed to identify 130 mutants Arabidopsis thaliana with defects female gametophyte function. wide variety phenotypes were observed, ranging from different stages early embryo sac apparently normal sacs, but exhibiting...
The directional growth of the pollen tube from stigma to embryo sac in ovules is regulated by pollen-pistil interactions based on intercellular communication. Although cytoplasmic Ca(2+) concentration ([Ca(2+)](cyt)), it not known whether [Ca(2+)](cyt) involved guidance and reception. Using Arabidopsis expressing GFP-based Ca(2+)-sensor yellow cameleon 3.60 (YC3.60) tubes synergid cells, we monitored dynamics these cells during reception under semi-in vivo fertilization conditions. In...
Abstract Parasitic plants in the Orobanchaceae develop haustoria response to contact with host roots or chemical haustoria-inducing factors. Experiments this manuscript test hypothesis that quinolic-inducing factors activate haustorium development via a signal mechanism initiated by redox cycling between quinone and hydroquinone states. Two cDNAs were previously isolated from of parasitic plant Triphysaria versicolor encode distinct oxidoreductases. QR1 encodes single-electron reducing NADPH...
The NuRD complex subunit CHD4 is essential for fusion-positive rhabdomyosarcoma (FP-RMS) survival, but the mechanisms underlying this dependency are not understood. Here, a NuRD-specific CRISPR screen demonstrates that FP-RMS particularly sensitive to amongst members. Mechanistically, containing localizes super-enhancers where generates chromatin architecture permissive binding of tumor driver and fusion protein PAX3-FOXO1, allowing downstream transcription its oncogenic program. Moreover,...
Abstract Cancer therapy is currently shifting from broadly used cytotoxic drugs to patient-specific precision therapies. Druggable driver oncogenes, identified by molecular analyses, are present in only a subset of patients. Functional profiling primary tumor cells could circumvent these limitations, but suitable platforms unavailable for most cancer entities. Here, we describe an vitro drug platform rhabdomyosarcoma (RMS), using living biobank composed twenty RMS patient-derived xenografts...
Abstract Rhabdomyosarcoma (RMS) is a pediatric malignancy of skeletal muscle lineage. The aggressive alveolar subtype characterized by t(2;13) or t(1;13) translocations encoding for PAX3- PAX7-FOXO1 chimeric transcription factors, respectively, and are referred to as fusion positive RMS (FP-RMS). gene alters the myogenic program maintains proliferative state while blocking terminal differentiation. Here, we investigated contributions chromatin regulatory complexes FP-RMS tumor maintenance....
Abstract Activation of oncogenic gene expression from long-range enhancers is initiated by the assembly DNA-binding transcription factors (TF), leading to recruitment co-activators such as CBP/p300 modify local genomic context and facilitate RNA-Polymerase 2 (Pol2) binding. Yet, most TF-to-coactivator relationships remain unmapped. Here, studying fusion TF PAX3-FOXO1 (P3F) alveolar rhabdomyosarcoma (aRMS), we show that a single cysteine in activation domain (AD) P3F important for small alpha...
Embryogenesis in Arabidopsis thaliana is marked by a predictable sequence of oriented cell divisions, which precede fate determination. We show that mutation the TORMOZ (TOZ) gene yields embryos with aberrant division planes and arrested appear not to have established normal patterning. The defects toz mutants differ from previously described mutations affect embryonic patterns. Longitudinal proembryo are frequently replaced transverse divisions less oblique while suspensor cells, divide...
Early seed development of sexually reproducing plants requires both maternal and paternal genomes but is prominently maternally influenced. A novel gametophytic maternal-effect mutant defective in early embryo endosperm development, glauce (glc), has been isolated from a population Arabidopsis Ds transposon insertion lines. The glc mutation results deletion at the site, molecular identity GLC not known. glcembryos can develop up to globular stage absence central cells appear be unfertilized....
The rhizosphere is teemed with organisms that coordinate their symbioses using chemical signals traversing between the host root and symbionts. Chemical also mediate interactions roots of different plants, perhaps most obvious being those parasitic Orobanchaceae plant hosts. Parasitic plants use specific molecules provided by to initiate development haustoria, invasive structures critical for parasitism. We took a transcriptomics approach identify genes associated factor recognition...
Double fertilization of the egg cell and central by two sperm cells, resulting in formation embryo endosperm, respectively, is a defining characteristic flowering plants. The Arabidopsis thaliana female gametophytic mutant glauce (glc) can exhibit development without any endosperm. Here, we show that glc sacs one successfully fuses with but second fails to fuse cell, single fertilization. Complementation studies using genes from deletion interval identified an unusual genomic locus having...
Abstract Ewing sarcoma is an aggressive cancer with a defective response to DNA damage leading enhanced sensitivity genotoxic agents. Mechanistically, driven by the fusion transcription factor EWS-FLI1, which reprograms tumor cell epigenome. The nucleosome remodeling and deacetylase (NuRD) complex important regulator of chromatin function, controlling both gene expression repair, has been associated EWS-FLI1 activity. Here, NuRD-focused CRISPR/Cas9 inactivation screen identified helicase...
The proper balance of parental genomic contributions to the fertilized embryo and endosperm is essential for their normal growth development. characterization many gametophytic maternal effect (GME) mutants affecting seed development indicates that there are certain classes genes with a predominant contribution. We present detailed analysis GME mutant zak ixik (zix), which displays delayed arrested at earliest stages ZIX encodes an Armadillo repeat (Arm) protein highly conserved across...
Plant parasitism represents an extraordinary interaction among flowering plants: parasitic plants use a specialized organ, the haustorium, to invade host vascular system deprive of water and nutrients. Various compounds present in exudates trigger haustorium development. The two most effective inducing factors (HIFs) known for plant Triphysaria versicolor (T. versicolor) are peonidin, antioxidant flavonoid, 2,6-dimethoxybenzoquinone (DMBQ), oxidative stress agent. To date, genes involved...
Abstract Most relapses of acute lymphoblastic leukemia (ALL) occur in patients with a medium risk (MR) for relapse on the Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL protocol, based persistence minimal residual disease (MRD). New insights into biological features that are associated MRD needed. Here, we identify glycosylphosphatidylinositol-anchored cell surface protein vanin-2 (VNN2; GPI-80) by charting proteome very high-risk (HR)...
The DEFECTIVE EMBRYO AND MERISTEMS 1 (DEM1) gene encodes a protein of unknown biochemical function required for meristem formation and seedling development in tomato, but it was unclear whether DEM1’s primary role cell division or alternatively, defining the identity meristematic cells. Genome sequence analysis indicates that flowering plants possess at least two DEM genes. Arabidopsis has genes, DEM1 DEM2 , which we show are expressed developing embryos meristems punctate pattern is typical...
Oncogenic transcription factors lacking enzymatic activity or targetable binding pockets are typically considered "undruggable". An example is provided by the EWS-FLI1 oncoprotein, whose continuous expression and as factor critically required for Ewing sarcoma tumor formation, maintenance, proliferation. Because neither upstream nor downstream targets have so far disabled its oncogenic potential, we performed a high-throughput drug screen (HTS), enriched FDA-approved drugs, coupled to Global...
Abstract As the second most common pediatric bone and soft tissue tumor, Ewing sarcoma (ES) is an aggressive disease with a pathognomonic chromosomal translocation t(11;22) resulting in expression of EWS-FLI1, “undruggable” fusion protein acting as transcriptional modulator. EWS-FLI1 rewires cancer cells by activating repressing multitude genes. The role contribution repressed genes remains unknown to date. To address this, we established CRISPR activation system clonal SKNMC cell lines...
<div>Abstract<p>Ewing sarcoma is an aggressive cancer with a defective response to DNA damage leading enhanced sensitivity genotoxic agents. Mechanistically, Ewing driven by the fusion transcription factor EWS-FLI1, which reprograms tumor cell epigenome. The nucleosome remodeling and deacetylase (NuRD) complex important regulator of chromatin function, controlling both gene expression repair, has been associated EWS-FLI1 activity. Here, NuRD-focused CRISPR/Cas9 inactivation...
<div>Abstract<p>Ewing sarcoma is an aggressive cancer with a defective response to DNA damage leading enhanced sensitivity genotoxic agents. Mechanistically, Ewing driven by the fusion transcription factor EWS-FLI1, which reprograms tumor cell epigenome. The nucleosome remodeling and deacetylase (NuRD) complex important regulator of chromatin function, controlling both gene expression repair, has been associated EWS-FLI1 activity. Here, NuRD-focused CRISPR/Cas9 inactivation...
<p>Supplementary Tables 1-14</p>
<p>Supplementary Figures 1-7 and supplementary material methods</p>
<p>Supplementary Figures 1-7 and supplementary material methods</p>