A5063357660- Protein Degradation and Inhibitors
- Chromatin Remodeling and Cancer
- Plant Reproductive Biology
- Epigenetics and DNA Methylation
- Plant Molecular Biology Research
- Multiple Myeloma Research and Treatments
- Plant and animal studies
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Gene expression and cancer classification
- Renal and related cancers
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Cancer Mechanisms and Therapy
- Extracellular vesicles in disease
- Cancer-related molecular mechanisms research
- Histone Deacetylase Inhibitors Research
- Photosynthetic Processes and Mechanisms
- Advanced Breast Cancer Therapies
- Electron and X-Ray Spectroscopy Techniques
- Botanical Research and Chemistry
- Transgenic Plants and Applications
- Cell Image Analysis Techniques
- Radiomics and Machine Learning in Medical Imaging
St. Jude Children's Research Hospital
2017-2023
Pennsylvania State University
2013-2022
Universal Technical Institute
1994
Petunia possesses self-incompatibility, by which pistils reject self-pollen but accept non-self-pollen for fertilization. Self-/non-self-recognition between pollen and pistil is regulated the pistil-specific S-RNase gene multiple pollen-specific S-locus F-box (SLF) genes. To date, 10 SLF genes have been identified various methods, seven shown to be involved in specificity. For a given S-haplotype, each interacts with subset of its non-self S-RNases, an as yet unknown number SLFs are thought...
S-RNase-based self-incompatibility in Petunia is a self/non-self recognition system that allows the pistil to reject self-pollen prevent inbreeding and accept non-self pollen for outcrossing. Cloning of S-RNase 1986 marked beginning nearly three decades intensive research into mechanism this complex system. was shown be sole female determinant 1994, first male determinant, S-locus F-box protein1 (SLF1), identified 2004. It discovered 2010 additional SLF proteins are involved specificity,...
Self-incompatibility (SI) in Petunia is regulated by a polymorphic S-locus. For each S-haplotype, the S-locus contains pistil-specific S-RNase gene and multiple pollen-specific F-box (SLF) genes. Both gain-of-function loss-of-function experiments have shown that alone regulates pistil specificity SI. Gain-of-function on SLF genes suggest entire suite of encoded proteins constitute pollen determinant. However, clear-cut must be performed to determine if are essential for SI pollen. Here, we...
Abstract The lack of model systems has limited the preclinical discovery and testing therapies for Wilms tumor (WT) patients who have poor outcomes. Herein, we establish 45 heterotopic WT patient-derived xenografts (WTPDX) in CB17 scid -/- mice that capture biological heterogeneity (WT). Among these total WTPDX, 6 from with diffuse anaplastic tumors, 9 experienced disease relapse, 13 bilateral are included. Early passage WTPDX show evidence clonal selection, evolution enrichment blastemal...
Single-cell RNA sequencing (scRNA-seq) is a powerful tool for characterizing the cell-to-cell variation and cellular dynamics in populations which appear homogeneous otherwise basic translational biological research. However, significant challenges arise analysis of scRNA-seq data, including low signal-to-noise ratio with high data sparsity, potential batch effects, scalability problems when hundreds thousands cells are to be analyzed among others. The inherent complexities dynamic nature...
Accounting for batch effects, especially latent in differential expression (DE) analysis is critical identifying true biological effects. Single-cell RNA sequencing (scRNA-seq) a powerful tool quantifying cell-to-cell variation transcript abundance and characterizing cellular dynamics. Although many scRNA-seq DE methods accommodate known variables, their performance has not been systematically evaluated. Moreover, the challenge of accounting variables largely unmet. In contrast, have...
Abstract Atypical teratoid/rhabdoid tumors (ATRTs) represent a rare, but aggressive pediatric brain tumor entity. They are genetically defined by alterations in the SWI/SNF chromatin remodeling complex members SMARCB1 or SMARCA4 . ATRTs can be further classified different molecular subgroups based on their epigenetic profiles. Although recent studies suggest that have distinct clinical features, subgroup-specific treatment regimens not been developed thus far. This is hampered lack of...
Abstract Developing synchronous bilateral Wilms tumor suggests an underlying (epi)genetic predisposition. Here, we evaluate this predisposition in 68 patients using whole exome or genome sequencing ( n = 85 tumors from 61 with matched germline blood DNA), RNA-seq 99 tumors), and DNA methylation analysis peripheral blood, 29 non-diseased kidney, tumors). We determine the predominant events for predisposition: 1)pre-zygotic genetic variants readily detectable [ WT1 (14.8%), NYNRIN (6.6%) ,...
Abstract Background CTCF is a well-established chromatin architectural protein that also plays various roles in transcriptional regulation. While biology has been extensively studied, how the domains of function to regulate transcription remains unknown. Additionally, original auxin-inducible degron 1 (AID1) system limitations investigating CTCF. Results We employ an improved technology, AID2, facilitate study acute depletion while overcoming previous AID system. As previously observed...
A frontier challenge in implementing femtosecond electron microscopy is to gain precise optical control of intense beams mitigate collective space charge effects for significantly improving the throughput. Here, we explore flexible uses an RF cavity as a longitudinal lens high-intensity beam column condensing both temporally and spectrally, relevant design ultrafast microscopy. Through introduction novel atomic grating approach characterization bunch phase optics, elucidate principles...
Self-incompatibility in Petunia is controlled by the polymorphic S-locus, which contains S-RNase encoding pistil determinant and 16-20 S-locus F-box (SLF) genes collectively pollen determinant. Here we sequenced assembled approximately 3.1 Mb of S2 -haplotype inflata using bacterial artificial chromosome clones containing all 17 SLF genes, SLFLike1, S-RNase. Two pseudogenes 28 potential protein-coding were identified, 20 also found at S-loci both S6a P. SN self-compatible axillaris, but not...
Summary Many flowering plants show self‐incompatibility, an intra‐specific reproductive barrier by which pistils reject self‐pollen to prevent inbreeding and accept non‐self pollen promote out‐crossing. In Petunia , the polymorphic S–locus determines self/non‐self recognition. The locus contains a gene encoding S– RN ase, controls pistil specificity, multiple S‐locus F‐box ( SLF ) genes that collectively control specificity. Each is component of SCF (Skp1/Cullin/F‐box) complex responsible...
The collaborative non-self-recognition model for S-RNase-based self-incompatibility predicts that multiple S-locus F-box proteins (SLFs) produced by pollen of a given S-haplotype collectively mediate ubiquitination and degradation all non-self S-RNases, but not self in the tube, thereby resulting cross-compatible pollination self-incompatible pollination. We had previously used extracts containing GFP-fused S2 -SLF1 (SLF1 with an -haplotype) Petunia inflata co-immunoprecipitation (Co-IP)...
Petunia inflata possesses a self-incompatibility (SI) mechanism, which involves S-RNase and multiple S-locus F-box (SLF) genes at the polymorphic S-locus. For given S-haplotype, each SLF is thought to interact with some of its non-self S-RNases, but not self S-RNase. In this work, we studied an allelic pair SLF1, S2-SLF1 S3-SLF1, differ in 44 amino acids show differential interactions S3-RNase. We first used vivo transgenic assay determine whether four chimeric proteins one three functional...
Abstract Although genome-wide DNA methylomes have demonstrated their clinical value as reliable biomarkers for tumor detection, subtyping, and classification, direct biological impacts at the individual gene level remain elusive. Here we present MethylationToActivity (M2A), a machine learning framework that uses convolutional neural networks to infer promoter activities based on H3K4me3 H3K27ac enrichment, from methylation patterns genes. Using publicly available datasets in real-world test...
Abstract This study comprehensively evaluated the landscape of genetic and epigenetic events that predispose to synchronous bilateral Wilms tumor (BWT). We performed whole exome or genome sequencing, total-strand RNA-seq, DNA methylation analysis using germline and/or samples from 68 patients with BWT St. Jude Children’s Research Hospital Oncology Group. found 25/61 (41%) harbored pathogenic likely variants, WT1 (14.8%), NYNRIN (6.6%), TRIM28 (5%) BRCA-related genes BRCA1 , BRCA2 PALB2 being...