- Occupational and environmental lung diseases
- Medical Imaging and Pathology Studies
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Pleural and Pulmonary Diseases
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Tissue Engineering and Regenerative Medicine
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Graphene and Nanomaterials Applications
- Pancreatic and Hepatic Oncology Research
- Ferroptosis and cancer prognosis
- Metastasis and carcinoma case studies
- Immune Cell Function and Interaction
- Neuroblastoma Research and Treatments
- Single-cell and spatial transcriptomics
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cancer-related molecular mechanisms research
- Radiomics and Machine Learning in Medical Imaging
- Immune cells in cancer
Brigham and Women's Hospital
2015-2024
Harvard University
2013-2024
Dana-Farber Brigham Cancer Center
2013
Dana-Farber Cancer Institute
2013
Virginia Tech
2010-2013
Massachusetts General Hospital
2010-2013
Center for Cancer Research
2011
Medicina
2011
National Cancer Institute
2011
Mesothelioma Applied Research Foundation
2008
Abstract Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining chest cavity. To expand our understanding MPM, we conducted comprehensive integrated genomic study, including most detailed analysis BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined novel subtype with TP53 SETDB1 mutations extensive loss heterozygosity. also report strong expression immune-checkpoint gene VISTA in epithelioid strikingly higher than...
Background —Left ventricular hypertrophy (LVH) represents both an adaptive response to increased cardiac work load and a precursor state of heart failure. Recent evidence linked myocyte death by apoptosis with LVH It remained unclear, however, whether participated in the transition from left dysfunction (LVD). Methods Results —Cardiac apoptotic events changes apoptosis-specific genes were studied rat model chronic pressure overload induced transverse aortic constriction. The geometry...
Cancers arise by the gradual accumulation of mutations in multiple genes. We now use shotgun pyrosequencing to characterize RNA and expression levels unique malignant pleural mesotheliomas (MPMs) not present control tissues. On average, 266 Mb cDNA were sequenced from each four MPMs, a pulmonary adenocarcinoma (ADCA), normal lung tissue. Previously observed differences MPM confirmed. Point identified using criteria that require presence mutation at least reads both strands absence sequence...
Activation of the stimulator interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding mechanism action in human tumors is key developing therapeutic combinations that activate effective innate immunity. Here, we report malignant pleural mesothelioma cells robustly express and are responsive agonist treatment ex vivo. Using dynamic single-cell RNA sequencing explants treated with a agonist, observed CXCR3...
Activation of AKT/protein kinase B promotes a variety biological activities important in tumorigenesis, such as cell survival and cycle progression. We previously demonstrated amplification overexpression the AKT2 gene subset human pancreatic carcinomas. In this investigation, we assessed catalytic activity 50 frozen tissues (37 carcinomas, four benign tumors nine normal pancreata) by vitro assay. Twelve 37 (32%) carcinomas showed markedly elevated levels compared to pancreata begin tumors....
Abstract Malignant mesothelioma has been linked to asbestos exposure and generally a poor prognosis because it is often diagnosed in advanced stages refractory conventional therapy. Human malignant mesotheliomas accumulate multiple somatic genetic alterations, including inactivation of the NF2 CDKN2A/ARF tumor suppressor genes. To better understand significance identify gene alterations that cooperate with loss function pathogenesis, we treated Nf2 (+/−) knockout mice induce mesotheliomas....
Polycomb group (PcG) proteins are critical epigenetic mediators of stem cell pluripotency, which have been implicated in the pathogenesis human cancers. This study was undertaken to examine frequency and clinical relevance PcG protein expression malignant pleural mesotheliomas (MPM).Microarray, quantitative reverse transcriptase PCR (qRT-PCR), immunoblot, immunohistochemistry techniques were used cultured MPM, mesothelioma specimens, normal mesothelial cells. Lentiviral short hairpin RNA...
Abstract Activation of the phosphatidylinositol-3-kinase (PI3K)/AKT survival pathway is a mechanism cytotoxic drug resistance in ovarian cancer, and inhibitors this can sensitize to drugs. The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) depletes some proteins involved PI3K/AKT signaling, e.g., ERBB2, epidermal growth factor receptor (EGFR), phosphorylated AKT (p-AKT). 17-AAG paclitaxel were combined (at fixed 1:1 ratio their IC50) four cancer cell lines that differ...
The current paradigm for elucidating the molecular etiology of cancers relies on interrogation small numbers genes, which limits scope investigation. Emerging second-generation massively parallel DNA sequencing technologies have enabled more precise definition cancer genome a global scale. We examined human primary malignant pleural mesothelioma (MPM) tumor and matched normal tissue by using combination sequencing-by-synthesis pyrosequencing methodologies to 9.6X depth coverage. Read density...
Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but associated with longer survival women. Insight into the advantage of female patients may advance molecular understanding MPM and identify therapeutic interventions will improve prognosis for all patients. In this study, we performed whole-genome sequencing tumor specimens from 10 matched control samples to potential driver mutations underlying MPM. We identified differences gender...
Abstract BRCA1‐associated protein‐1 ( BAP1 ) expression is commonly lost in several tumors including malignant pleural mesothelioma (MPM). Presence or absence of immunohistochemical nuclear staining tumor cells currently used for differential diagnosis MPM. In this study, a large cohort 596 MPM with available clinical data was analyzed to examine associations pattern and molecular features that may reflect the impact mutation on biology. Cases were classified according cells. Exome...
Abstract Purpose: Specificity protein 1 (SP1) is an oncogenic transcription factor overexpressed in various human malignancies. This study sought to examine SP1 expression malignant pleural mesotheliomas (MPM) and ascertain the potential efficacy of targeting these neoplasms. Experimental Design: qRT-PCR, immunoblotting, immunohistochemical techniques were used evaluate cultured MPM cells specimens normal mesothelial cells/pleura. MTS, chemotaxis, soft agar, β-galactosidase, Apo-BrdUrd...
Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer arising from the mesothelial cells of pleura. About 80% cases are linked to asbestos exposure, while remainder may be related prior chest radiation, genetic predisposition or spontaneous occurrence. We analyzed transcriptomes (n = 211), whole exomes 99), and targeted 103) 216 malignant tumors. Four distinct molecular subtypes, sarcomatoid (S), epithelioid (E), biphasic-E, biphasic-S were identified using RNA-seq data....