Liron D. Grossmann
A5051580744- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Protein Degradation and Inhibitors
- Lung Cancer Research Studies
- interferon and immune responses
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Radiomics and Machine Learning in Medical Imaging
- 3D Printing in Biomedical Research
- Cancer, Stress, Anesthesia, and Immune Response
- Acute Myeloid Leukemia Research
- Glioma Diagnosis and Treatment
- Cell death mechanisms and regulation
Children's Hospital of Philadelphia
2020-2025
Philadelphia University
2025
Edmond and Lily Safra Children's Hospital
2024-2025
Sheba Medical Center
2024-2025
University of Pennsylvania
2020
Significance Making immunotherapy more widely effective requires improved understanding of the pathways that regulate interactions between tumor and immune cells. This work identified a previously unappreciated difference in these heterogenous epigenetic states coexist neuroblastoma. The generally rarer mesenchymal subpopulation has active inflammatory sensing signaling, revealing potential immunologic vulnerability chemotherapy-resistant
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 Background Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype propose pan-neuroblastoma cell state specific targetable cell-surface proteins. Methods We characterized lines, patient-derived xenografts, patient samples as ADRN-dominant or MES-dominant to define subtype-specific...
Abstract High-risk neuroblastoma, a leading cause of pediatric cancer mortality, exhibits substantial intratumoral heterogeneity, contributing to therapeutic resistance. To understand tumor microenvironment evolution during therapy, we longitudinally profiled 22 patients with high-risk neuroblastoma before and after induction chemotherapy using single-nucleus RNA ATAC sequencing whole-genome sequencing. This revealed profound shifts in immune cell subpopulations therapy identified...
Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype propose pan-neuroblastoma cell state specific targetable cell-surface proteins.
Abstract Immunotherapy has revolutionized cancer treatment, but many cancers are not impacted by currently available immunotherapeutic strategies. Here, we investigated inflammatory signaling pathways in neuroblastoma, a classically “cold” pediatric cancer. By testing the functional response of panel 20 diverse neuroblastoma cell lines to three different stimuli, found that all have intact interferon and one lack cGAS-STING signaling. However, toll-like receptor (TLR) signaling, particularly...
Abstract The nucleosome remodeling factor BPTF is required for the deployment of MYC-driven transcriptional program. Deletion one Bptf allele delays tumor progression in mouse models pancreatic cancer and lymphoma. In neuroblastoma, MYCN cooperates with core regulatory circuitry (CRC). High levels are associated high-risk features decreased survival. depletion results a dramatic decrease cell proliferation. Bulk RNA-seq, single-cell sequencing, tissue microarrays reveal positive correlation...
Abstract Introduction: High-risk neuroblastoma (NBL) is a leading cause of pediatric cancer death and characterized by substantial intratumoral heterogeneity to therapeutic resistance. Despite the significant insights from recent single-cell sequencing, evolution tumor microenvironment under therapy remains obscure. We longitudinally profiled 22 high-risk NBL patients before after induction chemotherapy through single-nucleus RNA ATAC sequencing. identified profound shifts in immune cell...
Pearson syndrome (PS) and Kearns-Sayre (KSS) are single large-scale mitochondrial DNA deletion (SLSMD) syndromes. PS is characterized by severe, transient childhood cytopenia, whereas KSS typically manifests later in life without hematologic abnormalities. Despite distinct clinical presentations, both share a common deletion. Recent observations suggest potential link between progression myeloid malignancy development, indicating that bone marrow failure (BMF) may be key aspect of pathology...
<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...
Abstract BACKGROUND High-risk neuroblastoma is a pediatric cancer arising from the developing sympathetic nervous system with 50% relapse rate that typically fatal. At least two subpopulations of cells exist can transdifferentiate, adrenergic and mesenchymal, latter being more resistant to chemotherapy. Mechanisms therapy resistance are largely unknown responsible for have not been identified. METHODS We used single nucleus RNA ATAC sequencing identify characterize survive chemotherapy,...
Abstract Neuroblastoma is a childhood cancer originating from embryonic neuronal progenitor cells and the most common diagnosed in infants. Although majority of patients respond to initial chemotherapy, high-risk suffer relapse due therapy resistance. Here, we generated single-cell transcriptome bulk whole-genome sequencing data diagnosis post-therapy samples 23 with neuroblastoma. We found two distinct adrenergic populations patient samples. Most tumor showed mature sympathoblast phenotype...
Abstract Background: Neuroblastoma is an extracranial solid tumor of childhood that arises from the developing sympathetic nervous system. Half patients with high-risk disease do not survive despite multimodal therapy, and survival after relapse unlikely. Recent studies have characterized two distinct neuroblastoma cell subtypes: adrenergic (ADRN) subtype noradrenergic-like identity mesenchymal (MES) neural crest-like identity. ADRN-like cells are more aggressive proliferative, while...