A5002000126- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Neuroendocrine Tumor Research Advances
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- Immune cells in cancer
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- Cell death mechanisms and regulation
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- PI3K/AKT/mTOR signaling in cancer
- Congenital heart defects research
- DNA Repair Mechanisms
- Adrenal and Paraganglionic Tumors
- Histone Deacetylase Inhibitors Research
- Gene expression and cancer classification
Dana-Farber Cancer Institute
2016-2025
Harvard University
2016-2025
Boston Children's Hospital
2012-2024
University of Chicago
2024
Boston University
2023
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2020
University of California San Francisco Medical Center
2012
UCSF Helen Diller Family Comprehensive Cancer Center
2012
University of California, San Francisco
2012
University of California, San Diego
2012
Abstract Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive open-source toolbox for spatial data analysis visualization. The module provides end-to-end by implementing wide range of algorithms characterizing tissue composition, expression patterns, cellular interactions. Furthermore, single-cell RNAseq can be integrated cell-type enrichment analysis. visualization...
VHL , NF-1 c-Ret and Succinate Dehydrogenase Subunits B D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells requires the EglN3 prolyl hydroxylase as downstream effector. Germline mutations of these genes cause familial pheochromocytoma other neural crest-derived tumors. Using an unbiased shRNA screen we found kinesin KIF1Bβ acts from both necessary sufficient apoptosis NGF limiting. maps to chromosome...
Abstract Cyclin-dependent kinase 12 (CDK12) modulates transcription elongation by phosphorylating the carboxy-terminal domain of RNA polymerase II and selectively affects expression genes involved in DNA damage response (DDR) mRNA processing. Yet, mechanisms underlying such selectivity remain unclear. Here we show that CDK12 inhibition cancer cells lacking mutations results gene length-dependent defects, inducing premature cleavage polyadenylation (PCPA) loss long (>45 kb) genes, a...
We present the development of first small molecule degraders that can induce anaplastic lymphoma kinase (ALK) degradation, including in non-small-cell lung cancer (NSCLC), large-cell (ALCL), and neuroblastoma (NB) cell lines. These were developed through conjugation known pyrimidine-based ALK inhibitors, TAE684 or LDK378, cereblon ligand pomalidomide. demonstrate some types degrader potency is compromised by expression drug transporter ABCB1. In addition, proteomic profiling demonstrated...
To provide an update on long-term survival of patients with high-risk neuroblastoma treated tandem cycles myeloablative therapy and peripheral-blood stem-cell rescue (PBSCR).Ninety-seven were between 1994 2002. Patients underwent induction five standard agents, resection the primary tumor local radiation, two consecutive courses (including total-body irradiation) PBSCR.Fifty-one have experienced relapse or died. Median follow-up time among 46 who remain alive without progression is 5.6 years...
Abstract Neuroblastoma is a heterogeneous pediatric tumor thought to arise from the embryonic neural crest. Identification of cell responsible for propagating neuroblastomas essential understanding this often recurrent, rapidly progressing disease. We have isolated and characterized putative tumor-initiating cells 16 tumors bone marrow metastases patients in all neuroblastoma risk groups. Dissociated or grew as spheres conditions used culture crest stem cells, were capable self-renewal,...
Abstract Aggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene inactivation ATRX gene correlate with high-risk disease poor prognosis. Here we show that are mutually exclusive across all ages stages neuroblastoma. Using human cell lines mouse models, found elevated expression incompatible. Elevated levels promote metabolic reprogramming, mitochondrial dysfunction,...
Abstract Chromosome 17q21-ter is commonly gained in neuroblastoma, but it unclear which gene the region important for tumorigenesis. The JMJD6 at activates transcription. Here we show that forms protein complexes with N-Myc and BRD4, E2F2, c-Myc Knocking down reduces neuroblastoma cell proliferation survival vitro tumor progression mice, high levels of expression human tissues independently predict poor patient prognosis. In addition, associated transcriptional super-enhancers. Combination...
The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and 14 (METTL14). High levels METTL3/METTL14 drive the growth many types adult cancer, inhibitors are emerging as new anticancer agents. However, little known about epitranscriptome or role in neuroblastoma, common pediatric cancer. Here, we show METTL3 knockdown pharmacologic inhibition with small molecule...
Purpose To determine predictive strength of tumor cell ploidy and MYCN gene amplification on survival children older than 12 months with disseminated neuroblastoma (NB). Patients Methods Of 648 stage D NB enrolled onto the Pediatric Oncology Group Biology Study 9047 (1990-2000), 560 were assessable for amplification. Treatment patients varied; most receiving high-dose chemotherapy stem-cell rescue. Infants received standard chemotherapy, depending status ploidy. Results Among MYCN-amplified...