Laura Scolaro
A5012112191- Hippo pathway signaling and YAP/TAZ
- Neuroblastoma Research and Treatments
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Glioma Diagnosis and Treatment
- Biochemical Analysis and Sensing Techniques
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Cell death mechanisms and regulation
- Genetic factors in colorectal cancer
- Medical Imaging Techniques and Applications
- BRCA gene mutations in cancer
- Receptor Mechanisms and Signaling
- melanin and skin pigmentation
- Retinal Diseases and Treatments
- Cancer, Hypoxia, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Digestive system and related health
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Research Studies
- Metabolism, Diabetes, and Cancer
- Glaucoma and retinal disorders
- DNA Repair Mechanisms
Children's Hospital of Philadelphia
2018-2024
University of Pennsylvania
2015-2023
Thomas Jefferson University
2017
Temple University
2008-2016
University of Palermo
2007-2009
Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, Children's Brain Tumor Network (CBTN) Pacific Neuro-Oncology Consortium (PNOC) created a systematic process tumor biobanking, model generation, sequencing with immediate access to harmonized data. We leverage data establish OpenPBTA, an open collaborative project over 40 scalable...
The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9-mediated silencing locus increases relative sensitivity PDAC cells PARP inhibitors (PARPi). treated with PARPi stimulated translocation from nucleus cytoplasm, specifically promoting stabilization a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding unique sequence embedded in its 3' untranslated...
Abstract Relapsed neuroblastomas are enriched with activating mutations of the RAS–MAPK signaling pathway. The MEK1/2 inhibitor trametinib delays tumor growth but does not sustain regression in neuroblastoma preclinical models. Recent studies have implicated Hippo pathway transcriptional coactivator protein YAP1 as an additional driver relapsed neuroblastomas, well a mediator resistance other cancers. Here, we used highly annotated set high-risk cellular models to modulate expression and RAS...
Abstract Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance poorly understood. In this study, we used single-nucleus RNA sequencing bulk whole-genome to identify characterize the residual persister survive chemotherapy from a cohort 20 matched diagnosis definitive surgery tumor samples patients treated with induction chemotherapy. We show share common escape,...
Abstract Although leptin and its receptor (ObR) have emerged as important cancer biomarkers, the role of system in brain tumor development remains unknown. We screened 87 human biopsies using immunohistochemistry detected ObR 55.2% 60.9% cases, respectively. In contrast, were absent 14 samples normal tissue. The presence correlated with overall concordance 80.5%. leptin/ObR was highly expressed glioblastomas anaplastic astrocytomas, while lower expression both markers noted low‐grade...
Abstract Leptin, a multifunctional hormone, controls various processes in both the central nervous system and peripheral tissues. Because of presence multiple leptin/receptor (ObR) interaction sites diverse leptin activities, literature lacks truly monofunctional protein derivatives or fragments. To date, selective ObR antagonists have not been reported. We developed short, pharmacologically advantageous peptide analogs ObR‐binding site III that acted as inhibitors without any partial...
To design, manufacture and test a second generation leptin receptor (ObR) agonist glycopeptide derivative. The major drawback to current experimental therapies involving protein is the appearance of treatment resistance. Our novel peptidomimetic was tested for efficacy lack resistance induction in rodent models obesity appetite reduction.The containing two additional non-proteinogenic amino acids synthesized by standard solid-phase methods. Normal mice were fed with peanuts until their blood...
Leptin, a pluripotent adipokine, has been discovered as hormone controlling energy balance in hypothalamic neuroendocrine centers. In addition, recent studies provided ample evidence that leptin can be produced by cells other than adipocytes, and the regulate many physiological processes appetite. this context, it is not surprising both excess well insufficiency have implicated various pathologies. Consequently, despite initially disappointing results with recombinant drug for obesity...
BackgroundEmerging evidence suggests that angiogenic and pro-inflammatory cytokine leptin might be implicated in ocular neovascularization. However, the potential of inhibiting function ophthalmic cells has never been explored. Here we assessed mitogenic, angiogenic, signaling activities retinal corneal endothelial examined capability a specific receptor (ObR) antagonist, Allo-aca, to inhibit these functions. Methods ResultsThe experiments were carried out monkey (RF/6A) bovine (BCE) cells....
Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory mitogenic cytokine leptin can be implicated in ocular neovascularization other eye pathologies. At least part, action appears to mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis leakage proven role conditions such as proliferative diabetic retinopathy, age-related macular degeneration edema. Accordingly, drugs targeting are becoming...
Summary Pediatric brain and spinal cancer are the leading disease-related cause of death in children, thus we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, Children’s Brain Tumor Network Pacific Neuro-Oncology Consortium created a systematic process tumor biobanking, model generation, sequencing with immediate access to harmonized data. We leverage data create OpenPBTA, an open collaborative project which establishes over 40 scalable analysis...
<p>Supplementary Figure S1 shows cell type markers and inferred copy number of tumors as well characterization malignant, Schwann cells, tumor associated macrophages cancer fibroblasts at time definitive surgery</p>
<p>Supplementary Figure S4 differences in persister cell composition between diagnosis and definitive surgery as well decrease MYC/N protein level human samples, PDX lines following chemotherapy</p>
<p>Supplementary Figure S6 shows the increase in NF-kB activity following chemotherapy and its role survival which is enhanced by specific TAMs CAFs</p>
<p>Supplementary Figure S3 shows the WGS analysis of diagnostic and definitive surgery including clonal evolution ALK mutation from diagnosis to in one tumor.</p>
<p>Supplementary Figure S5 shows the connection between NF-kB/stemness subtype and mesenchymal transcriptional state.</p>
<p>Supplementary Figure S2 shows the details of pathway-based clustering algorithm including autocorrelation pathway scores, cell cycle annotation, enrichment analysis and region analysis.</p>
<div>Abstract<p>Relapse rates in high-risk neuroblastoma remain exceedingly high. The malignant cells that are responsible for relapse have not been identified, and mechanisms of therapy resistance poorly understood. In this study, we used single-nucleus RNA sequencing bulk whole-genome to identify characterize the residual persister survive chemotherapy from a cohort 20 matched diagnosis definitive surgery tumor samples patients treated with induction chemotherapy. We show share...