A5040848905- Meningioma and schwannoma management
- Glioma Diagnosis and Treatment
- Neurofibromatosis and Schwannoma Cases
- Neuroblastoma Research and Treatments
- Brain Metastases and Treatment
- Head and Neck Surgical Oncology
- Vascular Malformations Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- Sarcoma Diagnosis and Treatment
- Genomic variations and chromosomal abnormalities
- Pituitary Gland Disorders and Treatments
- DNA Repair Mechanisms
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Metal-Catalyzed Oxygenation Mechanisms
- NF-κB Signaling Pathways
- MXene and MAX Phase Materials
- interferon and immune responses
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Medical Imaging and Pathology Studies
University of California, San Francisco
2020-2024
Neurological Surgery
2020-2024
City College of San Francisco
2024
University of Birmingham
2016-2023
Southern Medical University Shenzhen Hospital
2021
Abstract Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, most common tumors peripheral nervous system. We find schwannomas comprised 2 molecular groups that distinguished by activation neural crest or nerve injury pathways specify tumor architecture immune microenvironment. Moreover, radiotherapy is sufficient for interconversion immune-enriched through metabolic...
Abstract Schwann cell tumors are the most common cancers of peripheral nervous system and can arise in patients with neurofibromatosis type-1 (NF-1) or type-2 (NF-2). Functional interactions between NF1 NF2 broader mechanisms underlying malignant transformation lineage unclear. Here we integrate bulk single-cell genomics, biochemistry, pharmacology across human samples, lines, mouse allografts to identify cellular de-differentiation driving treatment resistance. We find DNA methylation...
Advances in our understanding of the molecular biology meningiomas have led to significant gains ability predict patient prognosis and tumor recurrence identify novel targets for therapeutic design. Specifically, classification based on DNA methylation has greatly improved risk stratify patients, however new questions arisen terms underlying impact these DNA-methylation signatures meningioma biology.
Patients with biallelic truncating mutations in PALB2 have a severe form of Fanconi anaemia (FA-N), predisposition for developing embryonal-type tumours infancy. Here we describe two unusual patients from single family, carrying mutations, one truncating, c.1676_1677delAAinsG;(p.Gln559ArgfsTer2), and the second, c.2586+1G>A; p.Thr839_Lys862del resulting an frame skip exon 6 (24 amino acids). Strikingly, affected individuals did not exhibit developmental defects typical FA-N initially...
BACKGROUND AND OBJECTIVES: Meningiomas are the most common primary intracranial tumors and among only that can form lamellar, hyperostotic bone in tumor microenvironment. Little is known about epidemiology or molecular features of meningiomas. METHODS: Using a retrospective database 342 meningiomas treated with surgery at single institution, we correlated clinical, tumor-related, targeted next-generation DNA sequencing (n = 39 total, 16 meningioma-induced hyperostosis [MIH]), surgical...
SUMMARY Meningiomas arising from the meningothelial central nervous system lining are most common primary intracranial tumors, and a significant cause of neurologic morbidity mortality 1 . There no effective medical therapies for meningioma patients 2,3 , new treatments have been encumbered by limited understanding biology. DNA methylation profiling provides robust classification tumors 4 can elucidate targets molecular therapy 5 Here we use on 565 meningiomas integrated with genetic,...
Abstract BACKGROUND Meningiomas are the only primary tumors that form lamellar, hyperostotic bone in tumor microenvironment, but mechanisms drive meningioma-induced hyperostosis (MIH) incompletely understood. Clinical observations suggest TRAF7 short somatic variants (SSVs) enriched skull base meningiomas, and SSVs targeting WD40-domain may be associated with MIH. Here we use single-cell RNA sequencing lineage tracing approaches to study regionally distinct samples from meningiomas...
Introduction: Meningiomas are among the only tumors that can form lamellar, hyperostotic bone in tumor microenvironment. Mechanisms underlying meningioma-induced hyperostosis incompletely understood, but correlative genomic studies of human samples suggest TRAF7 missense mutations may promote formation meningioma Here we use functional approaches patient-derived cells and osteoblasts to shed light on biochemical mechanisms driving hyperostosis.
Abstract Meningiomas arising from the meningothelial central nervous system lining are most common primary intracranial tumors, and a significant cause of neurologic morbidity mortality1. There no effective medical therapies for meningioma patients2,3, new treatments have been encumbered by limited understanding biology. DNA methylation profiling provides robust classification tumors4, can elucidate targets molecular therapy5. Here we use on 565 meningiomas integrated with genetic,...
Meningiomas are the most common primary intracranial tumors and associated with inactivation of tumor suppressor
Abstract Jumonji-C (JmjC) ribosomal protein hydroxylases are an ancient class of oxygen- and Fe(II)-dependent oxygenases that spawned the wider JmjC family Histone Lysine Demethylases (KDMs) in eukaryotes. Myc-induced Antigen (MINA) has been implicated ribosome biogenesis was assigned as a nucleolar-localized histidyl hydroxylase large subunit RPL27A, consistent with reports it supports cell growth viability variety tumor types. Reported roles diverse aspects disease biology may be...
Abstract BACKGROUND Meningioma treatments are limited due to incomplete understanding of meningioma biology. To address this, we performed multiplatform molecular profiling on 565 meningiomas with comprehensive clinical data define genomic drivers and identify therapeutic vulnerabilities. METHODS DNA methylation was from UCSF (n=200, discovery) Hong Kong University (n=365, validation). Median follow-up 5.6 years, there were 388/142/35 WHO grade I/II/III meningiomas. Copy number variants...
Abstract BACKGROUND Alterations in the NF2 tumor suppressor gene lead to meningiomas and schwannomas, but functions of product, Merlin, are incompletely understood. To address this problem, we performed a structure-function analysis Merlin by expressing cancer-associated missense single-nucleotide variants (mSNVs) primary cancer cells for biochemical cell biology experiments. METHODS All mSNVs were assembled from cBioPortal COSMIC, modelled on FERM, a-helical, C-terminal domains (PDB 4ZRJ)...
Abstract Schwann cell tumors are the most common cancers of peripheral nervous system and can arise sporadically or in patients with neurofibromatosis type-1 (NF-1) type-2 (NF-2). NF-1 is caused by loss NF1, a negative regulator Ras signaling. NF-2 NF2, pleiotropic tumor suppressor that inhibits PAK Functional interactions between NF1 NF2 suppressors broader mechanisms underlying malignant transformation lineage unclear. Here, we integrate DNA methylation profiling, whole exome sequencing,...
Abstract How Merlin-intact meningiomas arise in the absence of NF2/Merlin inactivation is incompletely understood. Here, we integrate single-cell RNA sequencing 86,000 cells from meningioma xenografts with APEX2 proteomic proximity-labelling mass spectrometry and functional biochemical approaches to discover Merlin Serine 13 (S13) dephosphorylation drives Wnt signalling cell proliferation. Cell biology, molecular techniques were used validate functions or using wildtype constructs encoding...
Abstract Schwann cell derived tumors comprising schwannomas, neurofibromas, and malignant peripheral nerve sheath (MPNSTs) are the most common cancers of nervous system often arise in patients with neurofibromatosis type-1 (NF-1) or type-2 (NF-2). NF-1 is caused by loss NF1, a negative regulator Ras signaling, NF-2 NF2, pleiotropic tumor suppressor numerous functions including inhibition PAK signaling. However, whether functional interactions exist between NF1 NF2 suppressors remain unclear....