A5076166380- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Head and Neck Cancer Studies
- Meningioma and schwannoma management
- RNA modifications and cancer
- Cervical Cancer and HPV Research
- Ferroptosis and cancer prognosis
- Cancer-related gene regulation
- Hippo pathway signaling and YAP/TAZ
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Brain Metastases and Treatment
- RNA Research and Splicing
- T-cell and B-cell Immunology
- interferon and immune responses
- Neuroinflammation and Neurodegeneration Mechanisms
Massachusetts General Hospital
2010-2025
Harvard University
2010-2025
Washington University in St. Louis
2015-2024
Neurological Surgery
2015-2024
Harvard University Press
2024
Jewish Hospital
2016-2023
Barnes-Jewish Hospital
2016-2023
Alvin J. Siteman Cancer Center
2020-2023
Montana State University
2023
Saint Louis University Hospital
2022
Cancer immunoediting is the process whereby immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this hematopoietic cells represent critical targets of IFN’s actions. However, specific affected by IFN-α/β functional processes IFN induces remain undefined. Herein, we show required to initiate antitumor response its actions are temporally distinct from IFN-γ during cancer immunoediting. Using...
Purpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation multiple immune checkpoints, known contributor to failures amid checkpoint blockade, strategy that has lacked success thus far GBM. This study among first examine, credential as bona fide, T cells infiltrating human murine GBM.Experimental Design: Tumor-infiltrating...
We present the case of a patient with left frontal glioblastoma primitive neuroectodermal tumor features and hypermutated genotype in setting POLE germline alteration. During standard-of-care chemoradiation, developed cervical spine metastasis was subsequently treated pembrolizumab. Shortly thereafter, an additional metastatic spinal lesion. Using whole-exome DNA sequencing clonal analysis, we report changes subclonal architecture throughout treatment. Furthermore, persistently high...
Pembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result pathologic tumor response (pTR), lower the relapse rate resectable human papillomavirus (HPV)-unrelated HNSCC.Neoadjuvant (200 mg) was administered followed 2 3 weeks later by surgical ablation. Postoperative (chemo)radiation planned. Patients high-risk pathology (positive margins and/or...
A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, trials cooperative groups, patient advocacy groups to discuss challenges potential solutions for increasing development of therapeutics central nervous system metastases. key issue identified at this need consistent tumor measurement reliable response assessment, including first step standardized image acquisition with an MRI protocol that could be implemented in multicenter...
Abstract High-grade meningiomas frequently recur and are associated with high rates of morbidity mortality. To determine the factors that promote development evolution these tumors, we analyzed genomes 134 high-grade compared this information data from 595 previously published meningiomas. had a higher mutation burden than low-grade but did not harbor any significantly mutated genes aside NF2 . also possessed elevated chromosomal gains losses, especially among tumors monosomy 22. Meningiomas...
Abstract Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools ( www.regtools.org ), a computationally efficient, free, open-source software package designed to integrate somatic variants from genomic data with splice junctions bulk or single cell transcriptomic identify cause aberrant splicing. We apply over 9000 tumor samples both DNA RNA sequence data. discovers...
About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration anti-programmed death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the microenvironment (TME). However, mechanisms underlying dynamics antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, approaches to increase are lacking. In a phase 2 trial (NCT02296684), we...
Herein we report the generation of mouse monoclonal antibodies (mAbs) specific for IFNAR-1 subunit interferon-alpha/beta (IFN-alpha/beta) receptor (MAR1 mAbs) that block type I IFN signaling and biologic response induction in vitro vivo. These mAbs were generated from Ifnar1 (/) mice immunized by vivo hydrodynamic transfection with a plasmid encoding extracellular domain (ECD) murine IFNAR-1. All MAR1 bound native expressed on cell surfaces immunoprecipitated solubilized cells, two also...
Glioblastoma multiforme (GBM) is a fatal primary brain tumor harboring myriad genetic and epigenetic alterations. The recent multidimensional analysis of the GBM genome has provided more complete view landscape such alterations their linked pathways. This effort demonstrated that certain pathways are universally altered, but specific events altered within each pathway can vary for particular patient's tumor. With this atlas events, it now becomes feasible to assess how patterns mutations in...
Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality constitutes a global health challenge. To gain further insight into this disease, we generated line models from 7,12-dimethylbenz(a)anthracene-induced murine primary OSCC capable of tumor formation upon transplantation immunocompetent wild-type mice. Whereas several lines grew rapidly were metastasis, some slowly did not metastasize. Aggressively growing displayed ERK1/2 activation, which...
Upon stimulation by pathogen-associated inflammatory signals, TANK-binding kinase 1 (TBK1) induces type I interferon expression and modulates nuclear factor κB (NF-κB) signaling. Here, we describe the 2.4 Å-resolution crystal structure of nearly full-length TBK1 in complex with specific inhibitors. The reveals a dimeric assembly created an extensive network interactions among kinase, ubiquitin-like, scaffold/dimerization domains. An intact dimer undergoes K63-linked polyubiquitination on...