A5063678287- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Biosimilars and Bioanalytical Methods
- Immune cells in cancer
- Acute Lymphoblastic Leukemia research
- Molecular Biology Techniques and Applications
- T-cell and B-cell Immunology
- Cancer, Lipids, and Metabolism
- Bone and Joint Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Epigenetics and DNA Methylation
- Chronic Myeloid Leukemia Treatments
- Radiopharmaceutical Chemistry and Applications
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Bone Metabolism and Diseases
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Lung Cancer Treatments and Mutations
- Bone health and treatments
- CRISPR and Genetic Engineering
- Health, Environment, Cognitive Aging
- Mesenchymal stem cell research
University of Pennsylvania
2021-2025
Children's Hospital of Philadelphia
2023-2025
M S Ramaiah University of Applied Sciences
2024
California University of Pennsylvania
2024
University of Virginia Children's Hospital
2024
St. Jude Children's Research Hospital
2024
SickKids Foundation
2024
Hospital for Sick Children
2024
Great Ormond Street Hospital
2024
University College London
2024
Cancer cells are known to execute reprogramed metabolism of glucose, amino acids and lipids. Here, we report a significant role cholesterol in cancer metastasis. By using label-free Raman spectromicroscopy, found an aberrant accumulation cholesteryl ester human pancreatic specimens cell lines, mediated by acyl-CoA acyltransferase-1 (ACAT-1) enzyme. Expression ACAT-1 showed correlation with poor patient survival. Abrogation esterification, either inhibitor or shRNA knockdown, significantly...
The adoptive transfer of chimeric antigen receptor (CAR) T cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences autologously derived are major contributor to therapy failure. To interrogate the molecular determinants CAR T-cell persistence, we extensively characterized premanufacture 71 patients with B-cell malignancies on trial receive anti-CD19 therapy. We performed RNA-sequencing analysis sorted subsets from all patients, followed by...
Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) profile 29,325 non-hematopoietic discovered nine transcriptionally distinct subtypes. simultaneously profiled 53,417 hematopoietic predicted their interactions with subsets. employed co-detection by indexing (CODEX) spatially over 1.2 million cells. integrated scRNA-seq...
Colony-stimulating factor 1 (Csf1) is an essential growth for osteoclast progenitors and important regulator bone resorption. It remains elusive which mesenchymal cells synthesize Csf1 to stimulate osteoclastogenesis. We recently identified a novel cell population, marrow adipogenic lineage precursors (MALPs), in bone. Compared other subpopulations, MALPs expressed at much higher level this expression was further increased during aging. To investigate its role, we constructed MALP-deficient...
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30–40% patients develop resistance to imatinib therapy. Although most is caused by mutations in BCR-ABL domain, 50–85% these absence new mutations. In cases, targeting other pathways may be needed regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number cell lines discovered an aberrant...
Abstract The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these and their spatial organization remain largely uncharacterized as they have been technically challenging study in humans. Here, we used fresh femoral head samples performed single-cell RNA sequencing (scRNA-Seq) profile 29,325 enriched discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX)...
Abstract Bone resorption by osteoclasts is a critical step in bone remodeling, process important for maintaining homeostasis and repairing injured bone. We previously identified marrow mesenchymal subpopulation, adipogenic lineage precursors (MALPs), showed that its production of RANKL stimulates young mice using Adipoq-Cre . To exclude developmental defects to investigate the role MALPs-derived adult bone, we generated inducible reporter ( Adipoq-CreER Tomato ) deficient RANKLflox/flox,...
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...
Summary Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that a leading cause of pediatric cancer death. While pHGG shares many similarities to adult glioma, it increasingly recognized as molecularly distinct, yet highly heterogeneous disease. In this study, we longitudinally profiled diverse cohort 16 patients before and after standard therapy through single-nucleus RNA ATAC sequencing, whole-genome CODEX spatial proteomics capture the evolution tumor...
Refractoriness to initial chemotherapy and relapse after remission are the main obstacles curing T cell acute lymphoblastic leukemia (T-ALL). While tumor heterogeneity has been implicated in treatment failure, cellular genetic factors contributing resistance remain unknown. Here we linked subpopulations with clinical outcome, created an atlas of healthy pediatric hematopoiesis applied single-cell multiomic analysis a diverse cohort 40 T-ALL cases. We identified bone marrow progenitor...
Bilateral presentation of benign Struma ovarii is rare and has not been reported frequently in published literature. A 70-year-old postmenopausal female presented with progressive ascites, bilateral pleural effusion elevated CA-125 levels. The contrast-enhanced computed tomography (CECT) the abdomen pelvis revealed a heterogenous mass left adnexa. These findings were suspicious for an ovarian malignancy. After surgery diagnosis non functional, was made. specialized teratoma composed...
Muscle strips loaded with the Ca2+ indicator aequorin were studied in vitro to determine effects of inhibitory stimuli on force and cytosolic free Ca2+. In muscles contracted isometrically acetylcholine (ACh), 5-hydroxytryptamine (5-HT), carbachol, decreases muscle caused by isoproterenol (10(-5) M) or forskolin accompanied proportional luminescence. A similar relationship between luminescence was observed when relaxed stimulating Na+-K+-ATPase activity. These results suggest that...
Background Background: Mass cytometry (CyTOF) is a powerful tool for analyzing cellular networks at the single cell level. Due to high‐dimensional nature of this approach, analysis algorithms have been developed visualize and interpret mass data. In study, we applied these approaches cohort patients with secondary acute myeloid leukemia (sAML). Methods We utilized interrogate localization intensity thrombopoietin‐mediated intracellular signaling in sAML. Extracellular phenotypes were...
<title>Abstract</title> Refractoriness to initial chemotherapy and relapse after remission are the main obstacles cure in T-cell Acute Lymphoblastic Leukemia (T-ALL). Biomarker guided risk stratification targeted therapy have potential improve outcomes high-risk T-ALL; however, cellular genetic factors contributing treatment resistance remain unknown. Previous bulk genomic studies T-ALL implicated tumor heterogeneity as an unexplored mechanism for failure. To link subpopulations with...