A5033098575- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Nuclear Receptors and Signaling
- PI3K/AKT/mTOR signaling in cancer
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Brain Metastases and Treatment
Massachusetts General Hospital
2020-2024
Harvard University
2020-2024
Center for Cancer Research
2021-2024
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 Blood-borne metastasis to the brain is a major complication of breast cancer, but cellular pathways that enable cancer cells selectively grow in microenvironment are poorly understood. We find cultured circulating tumor (CTCs), derived from blood samples women with advanced and directly inoculated into mouse frontal lobe, exhibit striking differences proliferative potential brain. Derivative cell lines generated by serial intracranial injections acquire increased competency brain,...
Deregulation of oncogenic signals in cancer triggers replication stress. Immediate early genes (IEGs) are rapidly and transiently expressed following stressful signals, contributing to an integrated response. Here, we find that the orphan nuclear receptor NR4A1 localizes across gene body 3′ UTR IEGs, where it inhibits transcriptional elongation by RNA Pol II, generating R-loops accessible chromatin domains. Acute stress causes immediate dissociation a burst transcriptionally poised IEG...
Cancer therapy often results in heterogeneous responses different metastatic lesions the same patient. Inter- and intratumor heterogeneity signaling within various tumor compartments its impact on are not well characterized due to limited sensitivity of single-cell proteomic approaches. To overcome this barrier, we applied mass cytometry with a customized 26-antibody panel PTEN-deleted orthotopic prostate cancer xenograft models measure evolution kinase activities during metastasis or drug...
ABSTRACT The mitotic inhibitor docetaxel (DTX) is often used to treat endocrine-refractory metastatic breast cancer, but initial responses are mitigated as patients eventually have disease progression. Using a cohort of ex vivo cultures circulating tumor cells (CTCs) from with heavily pretreated cancer (n=18), we find two distinct patterns DTX susceptibility, independent clinical treatment history. In CTCs cultured some patients, single dose results in complete cell killing, associated...
Abstract Deregulation of oncogenic proliferative signals triggers replication stress in cancer cells to which they must adapt 1,2 . Immediate early genes (IEGs), identified by their rapid stress-induced transient bursts expression, are critical integrating downstream signaling pathways 3,4 In studying tumor initiation patient-derived breast cells, we observed acquisition open chromatin domains at the genebody and 3’-UTR IEGs, uniquely across genome. Through vivo vitro modeling, show that IEG...
ABSTRACT Cancer therapy often results in heterogeneous responses different metastatic lesions the same patient. Inter- and intra-tumor heterogeneity proteomic signaling within various tumor compartments its impact on are not well characterized due to limited sensitivity of single cell approaches. To overcome this barrier, we applied mass cytometry with a customized 29-antibody panel [against states, receptor tyrosine kinases (RTK) phosphoinositide 3-kinase/mammalian target rapamycin...