A5009207051- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Click Chemistry and Applications
- Ferroptosis and cancer prognosis
- Amino Acid Enzymes and Metabolism
- Histone Deacetylase Inhibitors Research
- Neuroblastoma Research and Treatments
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- PI3K/AKT/mTOR signaling in cancer
- Genomics and Chromatin Dynamics
- Speech Recognition and Synthesis
- Extracellular vesicles in disease
- Sirtuins and Resveratrol in Medicine
- Cancer, Lipids, and Metabolism
- Phonetics and Phonology Research
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
- Biological Research and Disease Studies
- Retinoids in leukemia and cellular processes
- Molecular Biology Techniques and Applications
Broad Institute
2012-2025
Dana-Farber Cancer Institute
2005-2025
Boston Children's Hospital
2006-2025
Harvard University
2014-2025
Center for Cancer Research
2015-2023
Massachusetts General Hospital
2006-2023
Dana-Farber/Boston Children's Cancer and Blood Disorders Center
2023
University of Oslo
2023
Oslo University Hospital
2023
Harvard Stem Cell Institute
2023
To pursue a systematic approach to the discovery of functional connections among diseases, genetic perturbation, and drug action, we have created first installment reference collection gene-expression profiles from cultured human cells treated with bioactive small molecules, together pattern-matching software mine these data. We demonstrate that this "Connectivity Map" resource can be used find molecules sharing mechanism chemicals physiological processes, diseases drugs. These results...
Abstract Androgen receptor (AR) plays a central role in prostate cancer, and most patients respond to androgen deprivation therapies, but they invariably relapse with more aggressive cancer that has been termed hormone refractory or independent. To identify proteins mediate this tumor progression, gene expression 33 androgen-independent bone marrow metastases versus 22 laser capture–microdissected primary cancers was compared using Affymetrix oligonucleotide microarrays. Multiple genes...
Abstract Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor ( EGFR ) mutations. However, relapse typically occurs after an average of 1 year continuous treatment. A fundamental histological transformation from NSCLC to small-cell cancer (SCLC) is observed in a subset the resistant cancers, but molecular changes associated this remain unknown. Analysis tumour samples and cell lines derived mutant patients revealed...
African American women are more likely to die as a result of breast cancer than white women. The influence somatic genomic profiles on this racial disparity is unclear. We aimed compare the distribution tumor characteristics and recurrence.We assessed with stage I III diagnosed from 1988 2013 primary tumors submitted Cancer Genome Atlas 2010 2014. used Cox proportional hazards models evaluate association race genetic traits investigated exome sequencing gene expression data in 663 711 105...
Despite extensive studies implicating tumor necrosis factor (TNF)-α as a contributing cause of insulin resistance, the mechanism(s) by which TNF-α alters energy metabolism in vivo and tissue specificity action are unclear. Here, we investigated effects infusion on gene expression adult rats. A 1-day treatment decreased overall sensitivity caused 70% increase (P = 0.005) plasma levels free fatty acids (FFAs) 46% decrease 0.01) ACRP30. 4-day resistance significant elevation FFAs triglycerides...
Abstract Androgen receptor (AR) plays a central role in prostate cancer, with most tumors responding to androgen deprivation therapies, but the molecular basis for this dependence has not been determined. [5α-dihydrotestosterone (DHT)] stimulation of LNCaP cancer cells, which have constitutive phosphatidylinositol 3-kinase (PI3K)/Akt pathway activation due PTEN loss, caused increased expression cyclin D1, D2, and D3 proteins, retinoblastoma protein hyperphosphorylation, cell cycle...
Abstract Genome-wide transcriptional profiling has shown that different biologic states (for instance, disease and response to pharmacologic manipulation) can be recognized by the expression pattern of relatively small numbers genes. However, lack a practical cost-effective technology for detection these gene 'signatures' in large samples severely limited their exploitation important medical pharmaceutical discovery applications. Here, we describe solution based on combination...
The worldwide burden of sickle cell disease is enormous, with over 200,000 infants born the each year in Africa alone. Induction fetal hemoglobin a validated strategy to improve symptoms and complications this disease. development targeted therapies has been limited by absence discrete druggable targets. We developed unique bead-based for identification inducers transcripts primary human erythroid cells. A small-molecule screen bioactive compounds identified remarkable class-associated...
JAK2 kinase inhibitors were developed for the treatment of myeloproliferative neoplasms (MPNs), following discovery activating mutations in majority patients with MPN. However, to date inhibitor has shown limited efficacy and apparent toxicities clinical trials. We report here that an HSP90 inhibitor, PU-H71, demonstrated cell line mouse models MPN polycythemia vera (PV) essential thrombocytosis (ET) by disrupting protein stability. physically associated both PU-H71 was degraded vitro vivo,...
Background Notch receptors normally play a key role in guiding variety of cell fate decisions during development and differentiation metazoan organisms. On the other hand, dysregulation Notch1 signaling is associated with many different types cancer as well tumor angiogenesis, making potential therapeutic target. Principal Findings Here we report vitro activities inhibitory monoclonal antibodies derived from cell-based solid-phase screening phage display library. Two classes were found, one...
Abstract Transcription factors (TFs) are frequently mutated in cancer. Paediatric cancers exhibit few mutations genome-wide but harbour sentinel that affect TFs, which provides a context to precisely study the transcriptional circuits support mutant TF-driven oncogenesis. A broadly relevant mechanism has garnered intense focus involves ability of TFs hijack wild-type lineage-specific self-reinforcing circuits. However, it is not known whether this specific type circuitry equally crucial all...
Background The presence of tumor-specific mutations in the cancer genome represents a potential opportunity for pharmacologic intervention to therapeutic benefit. Unfortunately, many classes oncoproteins (e.g., transcription factors) are not amenable conventional small-molecule screening. Despite identification somatic mutations, most therapy still utilizes nonspecific, cytotoxic drugs. One illustrative example is treatment Ewing sarcoma. Although EWS/FLI oncoprotein, present vast majority...