Scholars@Duke
Anoop Patel

Anoop Patel

Associate Professor of Neurosurgery
Neurosurgery

Selected Publications

A brave new framework for glioma drug development.

Journal Article Lancet Oncol · October 2024 Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Ini ... Full text Link to item Cite

Gene regulatory network topology governs resistance and treatment escape in glioma stem-like cells.

Journal Article Sci Adv · June 7, 2024 Poor prognosis and drug resistance in glioblastoma (GBM) can result from cellular heterogeneity and treatment-induced shifts in phenotypic states of tumor cells, including dedifferentiation into glioma stem-like cells (GSCs). This rare tumorigenic cell sub ... Full text Link to item Cite

Spatial transcriptomics reveals segregation of tumor cell states in glioblastoma and marked immunosuppression within the perinecrotic niche.

Journal Article Acta Neuropathol Commun · April 22, 2024 Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into ... Full text Open Access Link to item Cite

Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype.

Journal Article Genes Dev · April 17, 2024 Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an inde ... Full text Link to item Cite

Surgical Management and Advances in the Treatment of Glioma.

Journal Article Semin Neurol · December 2023 The care of patients with both high-grade glioma and low-grade glioma necessitates an interdisciplinary collaboration between neurosurgeons, neuro-oncologists, neurologists and other practitioners. In this review, we aim to detail the considerations, appro ... Full text Link to item Cite

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Journal Article Science · October 13, 2023 Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal ... Full text Link to item Cite

Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

Journal Article Science · October 13, 2023 Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (pat ... Full text Link to item Cite

CD8+ T cells maintain killing of MHC-I-negative tumor cells through the NKG2D-NKG2DL axis.

Journal Article Nat Cancer · September 2023 The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8+ T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, ... Full text Link to item Cite

WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma.

Journal Article Genes Dev · February 1, 2023 Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a ... Full text Link to item Cite

A single-cell based precision medicine approach using glioblastoma patient-specific models.

Journal Article NPJ Precis Oncol · August 8, 2022 Glioblastoma (GBM) is a heterogeneous tumor made up of cell states that evolve over time. Here, we modeled tumor evolutionary trajectories during standard-of-care treatment using multi-omic single-cell analysis of a primary tumor sample, corresponding mous ... Full text Link to item Cite

Automated objective surgical planning for lateral skull base tumors.

Journal Article Int J Comput Assist Radiol Surg · March 2022 PURPOSE: Surgical removal of pathology at the lateral skull base is challenging because of the proximity of critical anatomical structures which can lead to significant morbidity when damaged or traversed. Pre-operative computed surgical approach planning ... Full text Link to item Cite

Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons.

Journal Article Neuron · September 15, 2021 In the neocortex, subcerebral axonal projections originate largely from layer 5 (L5) extratelencephalic-projecting (ET) neurons. The unique morpho-electric properties of these neurons have been mainly described in rodents, where retrograde tracers or trans ... Full text Link to item Cite

A systems approach to brain tumor treatment

Journal Article Cancers · July 1, 2021 Brain tumors are among the most lethal tumors. Glioblastoma, the most frequent primary brain tumor in adults, has a median survival time of approximately 15 months after diagnosis or a five-year survival rate of 10%; the recurrence rate is nearly 90%. Unfo ... Full text Cite

Single-cell CUT&Tag analysis of chromatin modifications in differentiation and tumor progression.

Journal Article Nat Biotechnol · July 2021 Methods for quantifying gene expression1 and chromatin accessibility2 in single cells are well established, but single-cell analysis of chromatin regions with specific histone modifications has been technically challenging. In this study, we adapted the CU ... Full text Link to item Cite

Neural G0: a quiescent-like state found in neuroepithelial-derived cells and glioma.

Journal Article Mol Syst Biol · June 2021 Single-cell RNA sequencing has emerged as a powerful tool for resolving cellular states associated with normal and maligned developmental processes. Here, we used scRNA-seq to examine the cell cycle states of expanding human neural stem cells (hNSCs). From ... Full text Link to item Cite

Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles.

Journal Article Blood Adv · March 23, 2021 Vascular anomalies, including local and peripheral thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of deregulation of the cancer cell genome and epigenome. Although the molecular effectors of these changes are poorly understood, the upreg ... Full text Link to item Cite

The judicious use of stereotactic radiosurgery and hypofractionated stereotactic radiotherapy in the management of large brain metastases

Journal Article Cancers · January 1, 2021 Brain metastases are the most common intracranial malignant tumor in adults and are a cause of significant morbidity and mortality for cancer patients. Large brain metastases, defined as tumors with a maximum dimension >2 cm, present a unique clinical chal ... Full text Cite

The Future of Skull Base Surgery: A View Through Tinted Glasses.

Journal Article World Neurosurg · October 2020 In the present report, we have broadly outlined the potential advances in the field of skull base surgery, which might occur within the next 20 years based on the many areas of current research in biology and technology. Many of these advances will also be ... Full text Link to item Cite

Anti-PD-L1 antibody direct activation of macrophages contributes to a radiation-induced abscopal response in glioblastoma.

Journal Article Neuro Oncol · May 15, 2020 BACKGROUND: Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an "abscopal effect," whereby unirradiated neoplastic cells outside treatment sites are recognized and attacked by the ... Full text Link to item Cite

An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma.

Journal Article Cell · August 8, 2019 Diverse genetic, epigenetic, and developmental programs drive glioblastoma, an incurable and poorly understood tumor, but their precise characterization remains challenging. Here, we use an integrative approach spanning single-cell RNA-sequencing of 28 tum ... Full text Link to item Cite

Sternocleidomastoid Encephalomyosynangiosis for Treatment-Resistant Moyamoya Disease.

Journal Article Oper Neurosurg (Hagerstown) · July 1, 2019 BACKGROUND AND IMPORTANCE: Refractory ischemic symptoms in moyamoya disease are a challenging problem, particularly in situations in which multiple direct and indirect revascularization techniques have already been employed. In addition, revascularization ... Full text Link to item Cite

Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

Journal Article Lancet Neurol · May 2019 BACKGROUND: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive ... Full text Open Access Link to item Cite

Resection of Meningiomas Involving Major Dural Venous Sinuses: Classification, Technique, and Long-Term Results.

Journal Article World Neurosurg · May 2019 OBJECTIVE: Management of meningiomas with major dural venous sinus involvement is challenging. We present our case series and perspective on reconstruction of the sinuses. METHODS: Fifty-five patients underwent operations between 2005 and 2016 and the retr ... Full text Link to item Cite

Global, regional, and national burden of brain and other CNS cancer, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

Journal Article Lancet Neurol · April 2019 BACKGROUND: Brain and CNS cancers (collectively referred to as CNS cancers) are a source of mortality and morbidity for which diagnosis and treatment require extensive resource allocation and sophisticated diagnostic and therapeutic technology. Previous ep ... Full text Link to item Cite

Foreword

Book · January 1, 2019 Cite

Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq.

Journal Article Nat Commun · September 4, 2018 Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, we s ... Full text Link to item Cite

Surgical management of superior petrosal sinus dural arteriovenous fistulae with dominant internal carotid artery supply.

Journal Article Interv Neuroradiol · June 2018 Background While technological advances have improved the efficacy of endovascular techniques for tentorial dural arteriovenous fistulae (DAVF), superior petrosal sinus (SPS) DAVF with dominant internal carotid artery (ICA) supply frequently require surgic ... Full text Link to item Cite

Rapid Intraoperative in Situ Synthetic Cranioplasty.

Journal Article World Neurosurg · April 2018 Craniectomy is a frequently performed neurosurgical procedure, and coverage of the cranial defect is necessary for protection of the underlying brain, cosmesis, and patient satisfaction. We report a new technique for intraoperative in situ synthetic cranio ... Full text Link to item Cite

High-Grade Gliomas

Chapter · January 26, 2018 Full text Cite

Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer.

Journal Article Cell · December 14, 2017 The diverse malignant, stromal, and immune cells in tumors affect growth, metastasis, and response to therapy. We profiled transcriptomes of ∼6,000 single cells from 18 head and neck squamous cell carcinoma (HNSCC) patients, including five matched pairs of ... Full text Link to item Cite

Decoupling genetics, lineages, and microenvironment in IDH-mutant gliomas by single-cell RNA-seq.

Journal Article Science · March 31, 2017 Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-c ... Full text Link to item Cite

Adaptive Chromatin Remodeling Drives Glioblastoma Stem Cell Plasticity and Drug Tolerance.

Journal Article Cell Stem Cell · February 2, 2017 Glioblastoma, the most common and aggressive malignant brain tumor, is propagated by stem-like cancer cells refractory to existing therapies. Understanding the molecular mechanisms that control glioblastoma stem cell (GSC) proliferation and drug resistance ... Full text Link to item Cite

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma.

Journal Article Nature · November 10, 2016 Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give ri ... Full text Link to item Cite

Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment.

Journal Article J Neuropathol Exp Neurol · July 2015 Tissue hypoxia and necrosis represent pathophysiologic and histologic hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered ... Full text Link to item Cite

Multiplexed protein profiling after aneurysmal subarachnoid hemorrhage: characterization of differential expression patterns in cerebral vasospasm.

Journal Article J Clin Neurosci · December 2014 Cerebral vasospasm is a major contributor to delayed morbidity following aneurysmal subarachnoid hemorrhage. We sought to evaluate differential plasma protein levels across time in patients with aneurysmal subarachnoid hemorrhage to identify potential biom ... Full text Link to item Cite

EWS-FLI1 utilizes divergent chromatin remodeling mechanisms to directly activate or repress enhancer elements in Ewing sarcoma.

Journal Article Cancer Cell · November 10, 2014 The aberrant transcription factor EWS-FLI1 drives Ewing sarcoma, but its molecular function is not completely understood. We find that EWS-FLI1 reprograms gene regulatory circuits in Ewing sarcoma by directly inducing or repressing enhancers. At GGAA repea ... Full text Link to item Cite

Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma.

Journal Article Science · June 20, 2014 Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells ... Full text Link to item Cite

Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.

Journal Article Cell · April 24, 2014 Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal developmen ... Full text Link to item Cite

Clinical features of brain metastasis from salivary gland tumors.

Journal Article J Clin Neurosci · November 2013 Salivary gland tumors comprise a group of 24 tumor subtypes with a wide range of clinical behaviors and propensities for metastasis. Several prognostic factors have been identified that help predict the development of systemic metastases, most commonly to ... Full text Link to item Cite

An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma.

Journal Article Cell Rep · May 30, 2013 Glioblastoma (GBM) is thought to be driven by a subpopulation of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity yet remain poorly understood. Here, we present a comparative analysis of chromatin state in GBM CSCs that reveals ... Full text Link to item Cite

Expression of FMS-like tyrosine kinase 3 ligand by oncolytic herpes simplex virus type I prolongs survival in mice bearing established syngeneic intracranial malignant glioma.

Journal Article Neurosurgery · September 2012 BACKGROUND: Glioblastoma is a fatal brain tumor in needing urgent effective therapy. Treatments with both oncolytic viruses and immunotherapy have shown preclinical efficacy and clinical promise. We sought to exploit possible synergies between oncolytic he ... Full text Link to item Cite

Maintenance of primary tumor phenotype and genotype in glioblastoma stem cells.

Journal Article Neuro Oncol · February 2012 The clinicopathological heterogeneity of glioblastoma (GBM) and the various genetic and phenotypic subtypes in GBM stem cells (GSCs) are well described. However, the relationship between GSCs and the corresponding primary tumor from which they were isolate ... Full text Link to item Cite