A5066599334- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Prostate Cancer Treatment and Research
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Cancer-related molecular mechanisms research
- Cancer Immunotherapy and Biomarkers
- Molecular Biology Techniques and Applications
- Medical Imaging Techniques and Applications
- Bone health and treatments
- 3D Printing in Biomedical Research
- Breast Cancer Treatment Studies
- Advanced Breast Cancer Therapies
- Radiomics and Machine Learning in Medical Imaging
- Bioinformatics and Genomic Networks
- PI3K/AKT/mTOR signaling in cancer
- Melanoma and MAPK Pathways
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- RNA Research and Splicing
- Cancer, Hypoxia, and Metabolism
- Neural Networks and Applications
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Center for Cancer Research
2006-2025
ORCID
2020
Dana-Farber/Harvard Cancer Center
2018
New York Hospital Queens
2012
Howard Hughes Medical Institute
2012
NewYork–Presbyterian Hospital
2012
Presbyterian Hospital
2012
Cornell University
2012
Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis preclinical models. To investigate its role human cancer, we characterized EMT circulating (CTCs) from breast cancer patients. Rare primary simultaneously expressed and markers, but were highly enriched CTCs. Serial CTC monitoring 11 patients suggested an association CTCs with disease progression. In index patient, reversible shifts between these cell...
Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that isolation, ex vivo culture, and characterization CTCs may provide an opportunity to noninvasively monitor changing patterns drug susceptibility individual as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six estrogen receptor-positive breast cancer. Three five lines tested were tumorigenic mice....
Abstract Summary: While meta-analysis provides a powerful tool for analyzing microarray experiments by combining data from multiple studies, it presents unique computational challenges. The Bioconductor package RankProd new and intuitive this purpose in detecting differentially expressed genes under two experimental conditions. modifies extends the rank product method proposed Breitling et al., [(2004)FEBS Lett., 573, 83–92] to integrate studies different laboratories and/or platforms. It...
Circulating signals of drug resistance Cancer drugs often lose their effectiveness because tumors acquire genetic changes that confer resistance. Ideally, patients would be switched to a different before tumor growth resumes, but this requires early knowledge how arose. Miyamoto et al. have developed non-invasive method spot by sequencing RNA transcripts in single circulating cells (CTCs) (see the Perspective Nanus and Giannakakou). For example, prostate cancer patients, was triggered...
Highlights•Pancreatic CTCs can be enriched with antigen-agnostic microfluidic technology•Single-cell RNA sequencing of pancreatic reveals three distinct CTC populations•Extracellular matrix genes are highly expressed in mouse and human CTCs•The extracellular protein SPARC contributes to tumor metastasisSummaryCirculating cells (CTCs) shed from primary tumors into the bloodstream, mediating hematogenous spread cancer distant organs. To define their composition, we compared genome-wide...
Metastasis: A matter of translation? Solid tumors shed a small number cancer cells into the bloodstream, some which are believed to contribute metastasis. The molecular features that confer these circulating tumor (CTCs) with metastatic potential poorly understood. Ebright et al. studied CTCs from breast patients and found increased expression levels certain ribosomal proteins regulators translation had greater capacity in mouse model (see Perspective by Ma Jeffrey). Consistent this finding,...
Abstract Androgen deprivation therapy (ADT) is initially effective in treating metastatic prostate cancer, and secondary hormonal therapies are being tested to suppress androgen receptor (AR) reactivation castration-resistant cancer (CRPC). Despite variable responses AR pathway inhibitors CRPC, there no reliable biomarkers guide their application. Here, we used microfluidic capture of circulating tumor cells (CTC) measure signaling readouts before after therapeutic interventions. Single-cell...
Abstract Circulating tumor cells (CTC) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from patients with melanoma coordinately upregulate lipogenesis and iron homeostasis pathways. These correlated both intrinsic acquired resistance BRAF inhibitors across clonal cultures of BRAF-mutant CTCs. The regulator SREBP2 directly induces transcription carrier Transferrin (TF), reducing intracellular pools,...
Abstract Circulating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels force-amplifying magnetic lenses. Here, apply this technology to analyze patient-derived leukapheresis products, interrogating mean volume 5.83 liters from seven patients with...
Chemically induced birth defects are an important public health and human problem. Here we use Xenopus zebrafish as models to investigate the mechanism of action a well-known teratogen, valproic acid (VPA). VPA is drug used in treatment epilepsy bipolar disorder but causes spina bifida if taken during pregnancy. has several biochemical activities, including inhibition histone deacetylases (HDACs). To VPA, compared its effects embryos with those known HDAC inhibitors noninhibitory analogs. We...
Gene expression signatures are used in the clinic as prognostic tools to determine risk of individual patients with localized breast tumors developing distant metastasis. We lack a clear understanding, however, whether these correlative biomarkers link common biological network that regulates find c-MYC oncoprotein coordinately 13 different “poor-outcome” cancer signatures. In addition, functional inactivation MYC human cells specifically inhibits metastasis vivo and invasive behavior vitro...
There is an unmet clinical need for biomarkers to identify breast cancer patients at increased risk of developing brain metastases. The objective gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) metastasis.We combined laser capture microdissection expression microarrays analyze malignant epithelium from HER2+ metastases that nonmetastatic primary tumors. Differential was performed including set enrichment analysis (GSEA) using...
Metastasis confronts clinicians with two major challenges: estimating the patient's risk of metastasis and identifying therapeutic targets. Because they are key signal integrators connecting cellular processes to clinical outcome, we aimed identify transcriptional nodes regulating cancer cell metastasis. Using rodent xenograft models that previously developed, identified transcription factor Fos-related antigen-1 (Fra-1) as a coordinator Fra-1 often is overexpressed in human metastatic...
Significance Unique among the large number of noncoding RNA species, pericentromeric human satellite II (HSATII) repeat is massively expressed in a broad set epithelial cancers but nearly undetectable normal tissues. Here, we show that deregulation HSATII expression tightly linked to growth under nonadherent conditions, and uncover an unexpected mechanism by which RNA-derived DNA (rdDNA) leads progressive elongation regions tumors. The remarkable specificity overexpression cancers, together...
Abstract Purpose: Most node-negative breast cancer patients are older and postmenopausal increasingly being offered adjuvant chemotherapy despite their low overall risk of distant relapse. A molecular diagnostic test with high negative predictive value (NPV) for metastasis in this subgroup would spare many treatment. Experimental Design: We determined the NPV positive MammaPrint assay who were consecutively diagnosed treated at Massachusetts General Hospital between 1985 1997. Primary tumors...
Human tumors often contain slowly proliferating cancer cells that resist treatment, but we do not know precisely how these arise. We show rapidly can divide asymmetrically to produce “G0-like” progeny are enriched following chemotherapy in breast patients. Asymmetric cell division results from asymmetric suppression of AKT/PKB kinase signaling one daughter during telophase mitosis. Moreover, inhibition AKT with small-molecule drugs induce and the production slow proliferators. Cancer...
Significance Identifying predictive biomarkers of therapeutic response for melanoma patients treated with immune checkpoint inhibitors is a major challenge. By combining microfluidic enrichment circulating tumor cells (CTCs) together RNA-based droplet digital PCR quantitation, we have established highly sensitive and robust platform noninvasive, blood-based monitoring burden. Serial shows rapid changes in CTC score, which precede standard clinical assessment are long-term outcome. Early...
Abstract Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction β-globin ( HBB ), its partner α-globin HBA ). The tumour-specific origin is confirmed by sequence polymorphisms within human xenograft-derived mouse models. Increased intracellular reactive oxygen species...