A5001359015- Hedgehog Signaling Pathway Studies
- Single-cell and spatial transcriptomics
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- Cancer-related molecular mechanisms research
- Neutropenia and Cancer Infections
- Hematological disorders and diagnostics
- Ferroptosis and cancer prognosis
- Lymphoma Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- Retinal Development and Disorders
- Hippo pathway signaling and YAP/TAZ
- Immune cells in cancer
- Cellular transport and secretion
- Hematopoietic Stem Cell Transplantation
- Microtubule and mitosis dynamics
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- interferon and immune responses
- Redox biology and oxidative stress
Jackson Laboratory
2013-2025
St. Jude Children's Research Hospital
2016-2025
Genomics (United Kingdom)
2024
Stanford University
2020
Saarland University
2008-2018
Howard Hughes Medical Institute
2013
Maine Medical Center Research Institute
2013
Dana-Farber Cancer Institute
2013
The cerebellum develops from a restricted number of cell types that precisely organize to form the circuitry controls sensory-motor coordination and some higher-order cognitive processes. To acquire an enhanced understanding molecular processes mediate cerebellar development, we performed single-cell RNA-sequencing 39,245 murine cells at twelve critical developmental time points. Using recognized lineage markers, confirmed data accurately recapitulate development. We then followed distinct...
Significance Primary template-directed amplification (PTA) is a major improvement in whole genome amplification, which required to study intratissue cellular evolution. As presented the manuscript, PTA produces significantly improved and reproducible sequencing coverage variant detection from single of cell. Applications measuring genetic diversity cells with manuscript include examining acquisition changes during normal development aging, consequences specific perturbations such as editing,...
Synaptic ribbons are large, dynamic structures in the active zone complex of ribbon synapses and important for physiological properties these tonically synapses. RIBEYE is a unique major protein component synaptic ribbons. The aim present study was to understand how built construction could contribute its ultrastructural plasticity. In study, we demonstrate that self-associates using different independent approaches (yeast two-hybrid analyses, pull downs, ribbon–RIBEYE interaction assays,...
Bloodstream infection (BSI) is a common, life-threatening complication of treatment for cancer. Predicting BSI before onset clinical symptoms would enable preemptive therapy, but there no reliable screening test.
Survival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify small molecule CX-5461 as selectively cytotoxic to synergistic low picomolar concentrations of topoisomerase I inhibitors improving survival vivo orthotopic patient-derived xenograft mouse models. recently progressed through phase clinical trial a first-in-human inhibitor RNA-POL I. However, also use...
Abstract We present the first comprehensive investigation of clonal hematopoiesis (CH) in 2,860 long-term survivors pediatric cancer with a median follow-up time 23.5 years. Deep sequencing over 39 CH-related genes reveals mutations 15% survivors, significantly higher than 8.5% 324 community controls. CH is associated exposures to alkylating agents, radiation, and bleomycin. Therapy-related shows significant enrichment STAT3, characterized as gene specific Hodgkin lymphoma, TP53. Single-cell...
A lack of relevant genetic models and cell lines hampers our understanding hepatoblastoma pathogenesis the development new therapies for this neoplasm. Here, we report an improved MYC-driven hepatoblastoma-like murine model that recapitulates pathological features embryonal type hepatoblastoma, with transcriptomics resembling high-risk gene signatures human disease. Single-cell RNA-sequencing spatial identify distinct subpopulations cells. After deriving from mouse model, map cancer...
Abstract Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization gene expression within whole-tissue sections, but current approaches remain plagued challenge achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome...
Abstract Background Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need better understanding of the relationship between patient tumor heterogeneity and models. Results Here, generate single-cell RNA-seq maps neuroblastoma cell lines, patient-derived xenograft models (PDX), genetically engineered mouse model (GEMM). We...
Ribbon synapses continuously transmit graded membrane potential changes into of synaptic vesicle exocytosis and rely on intense trafficking. The ribbon is considered central to this process. In the present study we asked whether tonically active are associated with generation certain lipids, specifically highly signaling phospholipid phosphatidic acid (PA). Using PA-sensor proteins, demonstrate that PA enriched at mouse retinal in close vicinity situ. As shown by heterologous expression,...
Intra-tumor heterogeneity stems from genetic, epigenetic, functional, and environmental differences among tumor cells. A major source of genetic comes DNA sequence and/or whole chromosome focal copy number variations (CNVs). Whole CNVs are caused by chromosomal instability (CIN) that is defined a persistently high rate mis-segregation. Accordingly, CIN causes constantly changing karyotypes result in extensive cell-to-cell heterogeneity. How the influences gene expression individual cells...
Abstract While activation of the Notch pathway is observed in many human cancers, it unknown whether elevated Notch1 expression sufficient to initiate tumorigenesis most tissues. To test oncogenic potential solid tumors, we expressed an activated form (N1ICD) developing mouse brain. N1ICD;hGFAP-cre mice were viable but developed severe ataxia and seizures, died by weaning age. Analysis transgenic embryo brains revealed that N1ICD induced p53-dependent apoptosis. When apoptosis was blocked...
<div>Abstract<p>c-MYC is an important driver of high-risk neuroblastoma. A lack c-MYC–driven genetically engineered mouse models (GEMM) has hampered the ability to better understand mechanisms neuroblastoma oncogenesis and develop effective therapies. In this study, we showed that conditional c-MYC induction via Cre recombinase driven by a tyrosine hydroxylase promoter led preponderance <i>PDX1</i><sup>+</sup> somatostatinoma, type pancreatic...
<p>Supplementary Data including 12 figures and table S1</p>
The molecular mechanisms driving sex disparities in cancer prevalence, progression, and treatment outcomes represent a crucial yet understudied area with significant implications for therapy. Medulloblastoma (MB), exhibits pronounced bias incidence survival rates, males experiencing higher poorer prognoses compared to females. This study focused on the role of Yap1 Sonic Hedgehog medulloblastomas (SHH MBs), which revealed an unanticipated sex-biased MB immune evasion. Hippo/Yap pathway is...
Abstract Recently we and others reported high prevalence of clonal hematopoiesis (CH) in long-term survivors pediatric cancers by performing ultra-deep panel sequencing peripheral blood samples, a phenomena significantly associated with exposures to radiotherapy chemotherapeutic agents. Motivated preliminary finding that therapy-related STAT3 CH mutations were highly enriched T-cells 3 Hodgkin’s Lymphoma (HL) survivors, initiated systematic investigation map the across different immune cells...
Research Article28 September 2018Open Access Source DataTransparent process Early auto-immune targeting of photoreceptor ribbon synapses in mouse models multiple sclerosis Mayur Dembla Corresponding Author [email protected] orcid.org/0000-0002-0912-6828 Department Neuroanatomy, Institute Anatomy and Cell Biology, Medical School, Saarland University, Homburg, Germany Search for more papers by this author Ajay Kesharwani Sivaraman Natarajan Claudia Fecher-Trost Experimental Clinical...
The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. same developmental makes it difficult identify specific markers that discern between intraembryonic versus YS-origin using a lineage trace approach. Additionally, highly migratory nature blood cells and inability pre-circulatory (i.e., 5-7 somite pairs (sp))...
Guanylate cyclase activating protein 2 (GCAP2) is a recoverin-like Ca 2+ -sensor known to modulate guanylate activity in photoreceptor outer segments. GCAP2 also present ribbon synapses where its function unknown. Synaptic ribbons are active zone-associated presynaptic structures the tonically and contain RIBEYE as unique major component. In study, we demonstrate by various independent approaches that specifically interacts with synapses. We show flexible hinge linker region of RIBEYE(B)...