A5021909111- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Research Studies
- Lung Cancer Treatments and Mutations
- Advanced Breast Cancer Therapies
- Autophagy in Disease and Therapy
- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- FOXO transcription factor regulation
- NF-κB Signaling Pathways
- Neuroendocrine Tumor Research Advances
- RNA Interference and Gene Delivery
- Pancreatic function and diabetes
- RNA Research and Splicing
- Protein Tyrosine Phosphatases
- Ovarian cancer diagnosis and treatment
- Endometrial and Cervical Cancer Treatments
- MicroRNA in disease regulation
- Virus-based gene therapy research
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
The University of Texas MD Anderson Cancer Center
2024
University of Utah
2015-2024
Huntsman Cancer Institute
2018-2024
University of California, San Francisco
2014-2015
Massachusetts Institute of Technology
2009-2014
Harvard University
2009-2014
Brigham and Women's Hospital
2009-2014
Koch Institute for Integrative Cancer Research At MIT
2009-2013
IIT@MIT
2012
Dana-Farber/Harvard Cancer Center
2011
Macroautophagy (autophagy hereafter) degrades and recycles proteins organelles to support metabolism survival in starvation. Oncogenic Ras up-regulates autophagy, Ras-transformed cell lines require autophagy for mitochondrial function, stress survival, engrafted tumor growth. Here, the essential gene autophagy-related-7 ( atg7 ) was deleted concurrently with K-ras G12D activation mouse models non-small-cell lung cancer (NSCLC). -deficient tumors accumulated dysfunctional mitochondria...
Predicting drug response in cancer patients remains a major challenge the clinic. We have perfected an ex vivo, reproducible, rapid and personalized culture method to investigate antitumoral pharmacological properties that preserves original microenvironment. Response signal transduction inhibitors is determined not only by of target but also mutations other signaling molecules tumor As proof concept, we, therefore, focused on PI3K/Akt pathway, because it plays prominent role its activity...
Cellular identity and differentiation are determined by epigenetic programs. The characteristics of these programs in normal human mammary epithelium their similarity to those stem cells unknown. To begin investigating issues, we analyzed the DNA methylation gene expression profiles distinct subpopulations epithelial using MSDK (methylation-specific digital karyotyping) SAGE (serial analysis expression). We identified discrete cell-type state-specific patterns that were maintained a subset...
Advanced-stage peritoneal carcinomatosis is resistant to current chemotherapy treatment and, in the case of metastatic ovarian cancer, results a devastating 15%-20% survival rate. Therapeutics that restore genes inactivated during oncogenesis are predicted be more potent and specific than therapies. Experiments with viral vectors have demonstrated theoretical utility expressing p53 tumor suppressor gene cancer cells. However, clinically useful alternative approaches for introducing activity...
Small cell lung cancer (SCLC) is an aggressive often diagnosed after it has metastasized. Despite the need to better understand this disease, SCLC remains poorly characterized at molecular and genomic levels. Using a genetically engineered mouse model of driven by conditional deletion Trp53 Rb1 in lung, we identified several frequent, high-magnitude focal DNA copy number alterations SCLC. We uncovered amplification novel, oncogenic transcription factor, Nuclear factor I/B (Nfib), human...
Well-differentiated/dedifferentiated liposarcomas (WD/DDLPS) are among the most common subtypes of soft tissue sarcomas. Conventional systemic chemotherapy has limited efficacy and novel therapeutic strategies needed to achieve better outcomes for patients. The cyclin-dependent kinase 4 (CDK4) gene is highly amplified in more than 95% WD/DDLPS. In this study, we explored role CDK4 effects NVP-LEE011 (LEE011), a selective inhibitor CDK4/CDK6, on panel human liposarcoma cell lines primary...
Despite the fact that majority of lung cancer deaths are due to metastasis, molecular mechanisms driving metastatic progression poorly understood. Here, we present evidence loss Foxa2 and Cdx2 synergizes with Nkx2-1 fully activate program. These three lineage-specific transcription factors consistently down-regulated in cells compared nonmetastatic cells. Knockdown these acts synergistically is sufficient promote potential naturally arising vivo. Furthermore, silencing account for a...
Changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments growth KRAS-driven lung adenocarcinoma causes to gastric transdifferentiation. Here, we show that transcription factors FoxA1 FoxA2 are required for initiation mucinous NKX2-1-negative adenocarcinomas mouse activation their differentiation program. Foxa1/2 deletion severely impairs tumor a proximal shift cellular identity, yielding tumors expressing...
Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism progression from well-differentiated to dedifferentiated liposarcoma. To further define the role in liposarcoma progression, we performed immunohistochemistry for activating kinase ASK1 on series liposarcomas (n = 81). We correlated results with fluorescence situ hybridization detect amplification. also derived new cell lines protein is expressed majority (91%) their components (59%), but only...
The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human adenocarcinoma. To study transcriptional impact amplification, we generated an expression signature associated with amplification adenocarcinoma and analyzed DNA-binding sites by genome-wide chromatin immunoprecipitation. Integration these cistromic analyses identified LMO3 , itself encoding regulator, as candidate direct target NKX2-1. Further overexpression indicated...
Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval covalent inhibitors G12C such as sotorasib or adagrasib, oncoproteins are important pharmacological targets non-small cell cancer (NSCLC). However, not all -driven NSCLCs respond to these inhibitors, emergence drug resistance those patients who do can be rapid pleiotropic. Hence, based on a backbone inhibition , efforts underway develop effective combination...
Abstract Protein transduction domains (PTDs), such as the TAT PTD, have been shown to deliver a wide variety of cargo in cell culture and treat preclinical models cancer cerebral ischemia. The PTD enters cells by lipid raft–dependent macropinocytosis mechanism that all perform. Consequently, PTDs resemble small-molecule therapeutics their lack pharmacologic tissue specificity vivo. However, several human malignancies overexpress specific receptors, including HER2 breast cancer, GnRH ovarian...
Well-differentiated liposarcoma (WDLPS), one of the most common human sarcomas, is poorly responsive to radiation and chemotherapy, lack animal models suitable for experimental analysis has seriously impeded functional investigation its pathobiology development effective targeted therapies. Here, we show that zebrafish expressing constitutively active Akt2 in mesenchymal progenitors develop WDLPS closely resembles disease. Tumor incidence rates were 8% p53 wild-type zebrafish, 6%...
Genomic amplification of the c-Jun proto-oncogene has been identified in ∼30% dedifferentiated liposarcomas (DDLPS), but functional contribution to progression DDLPS remains poorly understood. In previous work we showed that knock-down by RNA interference impaired vitro proliferation and vivo growth a cell line (LP6) with genomic locus. Here, used gene expression analysis studies broad panel lines further define role other soft tissue sarcomas. We show impairs transition through G1 phase...