A5014838325- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Radiomics and Machine Learning in Medical Imaging
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- Sarcoma Diagnosis and Treatment
- Tuberculosis Research and Epidemiology
- RNA Research and Splicing
- Medical Imaging Techniques and Applications
- RNA modifications and cancer
- Genomics, phytochemicals, and oxidative stress
- Metabolism, Diabetes, and Cancer
- Genetic and Kidney Cyst Diseases
- Immune cells in cancer
- Immune Cell Function and Interaction
- Pulmonary Hypertension Research and Treatments
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Systemic Sclerosis and Related Diseases
- Wnt/β-catenin signaling in development and cancer
- Mathematical Biology Tumor Growth
- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
Harvard University
2015-2025
Massachusetts General Hospital
2015-2024
Center for Cancer Research
2024
Duke University
2016-2020
Brigham and Women's Hospital
1980
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...
Purpose: The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non–small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation TKIs that overcome T790M-associated resistance available, noninvasive approaches detection will critical guide management.Experimental Design: part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis 40 patients with tumors progressing on...
Highlights•Fatty acid oxidation increases global histone acetylation•Lipids can provide up to 90% of acetyl-carbon for acetylation•Octanoate reprograms metabolism and becomes the major source acetyl-CoA•Lipid-derived acetyl-CoA promotes lipid-specific gene expressionSummaryCells integrate nutrient sensing coordinate proper cellular responses a particular source. For example, glucose drives expression program characterized by activating genes involved in its metabolism, part increasing...
Tumor relapse is the leading cause of death in breast cancer, largely due to fact that recurrent tumors are frequently resistant chemotherapy. We previously reported downregulation proapoptotic protein Par-4 promotes tumor recurrence genetically engineered mouse models cancer recurrence. In present study, we examined mechanism and functional significance tumors. found epithelial-to-mesenchymal transition (EMT) epigenetic silencing proceeded through binding EMT transcription factor Twist...
Abstract The survival and recurrence of residual tumor cells following therapy constitutes one the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how clonal composition tumors changes during relapse. We use cellular barcoding monitor dynamics vivo. find that diversity decreases regression, disease, recurrence. dormant follows several distinct routes. Approximately half recurrent exhibit dominance with a small number subclones comprising vast majority tumor;...
Abstract Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation expression, leading heterogeneity subclonal resistance.
E3 ubiquitin ligases mediating turnover of proteins engaged in cancer progression point to key regulatory nodes. To uncover modifiers metastatic competency, we conducted an vivo genome-wide CRISPR-inactivation screen using cultured breast circulating tumor cells, following intravascular seeding and lung colonization. We identified HECTD4, a previously uncharacterized gene encoding conserved potential HECT domain-containing transferase, as potent metastasis suppressor. show that purified...
Abstract E3 ubiquitin ligases mediating turnover of proteins engaged in cancer progression point to key regulatory nodes. To uncover modifiers metastatic competency, we conducted an vivo genome-wide CRISPR-inactivation screen using cultured breast circulating tumor cells, following intravascular seeding and lung colonization. We identified HECTD4, a previously uncharacterized gene encoding conserved potential HECT domain-containing transferase, as potent suppressor. show that purified HECTD4...
Abstract With the large number of women diagnosed and treated for breast cancer each year, importance studying recurrence has become evident due to most deaths from resulting tumor following therapy. To mitigate this, cellular molecular pathways used by residual disease prior must be studied. An altered metabolism long been considered a hallmark cancer, several recent studies have gone further report metabolic dysfunction alterations as key understanding underlying behavior dormant recurrent...
Abstract A case is reported of a 29‐year‐old woman with systemic lupus erythematosus (SLE) who developed clinical manifestations pulmonary hypertension at time when other SLE were quiescent. She had restrictive ventilatory defect but clear lung fields on chest x ray. Cardiac catheterization revealed severe hypertension. Calculated vascular resistance fell slightly after administration oxygen and during infusion vasodilators. Symptomatic improvement modest increase in right ventricular...
Abstract Branched-chain amino acid metabolism has emerged as a crucial regulator of tumor proliferation. In particular, the branched-chain transaminase 1 (BCAT1), which catalyzes conversion acids to α-keto in cytoplasm, been identified promising therapeutic target for several different cancer types, including gliomas and leukemias. BCAT1 expression also associated with resistance anti-estrogen therapy breast cancer, suggesting role progression. Yet functional promoting recurrence not...
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...
Summary Oncogenic signaling pathways both directly and indirectly regulate anabolic metabolism, this is required for tumor growth. Targeted therapies that inhibit oncogenic have dramatic impacts on cellular metabolism. However, it not known whether the acquisition of resistance to these associated with – or driven by alterations in To address this, we used a conditional mouse model Her2-driven breast cancer study metabolic adaptations following Her2 inhibition, during residual disease, after...
Summary The survival of residual tumor cells following therapy and their eventual recurrence constitutes one the biggest obstacles to obtaining cures in breast cancer, but it remains unclear how clonal composition tumors changes during relapse. We used cellular barcoding directly monitor dynamics a genetically engineered mouse model. found that diversity progressively decreased regression, disease, recurrence. Only fraction subclones survived oncogene withdrawal persisted tumors. minimal...
<p>Supplementary Figures S1-S3. Supplementary Figure S1: T790M CTC PointMan genotyping assay. S2: concordance by method. S3: Concordance of L858R and Ex 19 deletion ctDNA tissue biopsy.</p>
<div>Abstract<p><b>Purpose:</b> The T790M gatekeeper mutation in the <i>EGFR</i> is acquired by some <i>EGFR</i>-mutant non–small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance available, noninvasive approaches detection will critical guide management.</p><p><b>Experimental Design:</b> part of a...
<div>Abstract<p><b>Purpose:</b> The T790M gatekeeper mutation in the <i>EGFR</i> is acquired by some <i>EGFR</i>-mutant non–small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance available, noninvasive approaches detection will critical guide management.</p><p><b>Experimental Design:</b> part of a...
<p>Supplementary Figures S1-S3. Supplementary Figure S1: T790M CTC PointMan genotyping assay. S2: concordance by method. S3: Concordance of L858R and Ex 19 deletion ctDNA tissue biopsy.</p>
<div>Abstract<p>With the large number of women diagnosed and treated for breast cancer each year, importance studying recurrence has become evident due to most deaths from resulting tumor following therapy. To mitigate this, cellular molecular pathways used by residual disease prior must be studied. An altered metabolism long been considered a hallmark cancer, several recent studies have gone further report metabolic dysfunction alterations as key understanding underlying...
<p>Supplementary Figure 1: 3D Rendering of mammosphere stained with 2-NBDG and TMRE. Supplementary 2: Western blot confirms loss Her2 expression following withdrawal Dox in media conditions. 3: Quantification immunohistochemistry results confirm changes proliferation apoptosis. 4: Average TMRE per group across each time point. 5: Annexin V flow cytometry show increased is independent apoptosis.</p>
<p>Supplementary Figure 1: 3D Rendering of mammosphere stained with 2-NBDG and TMRE. Supplementary 2: Western blot confirms loss Her2 expression following withdrawal Dox in media conditions. 3: Quantification immunohistochemistry results confirm changes proliferation apoptosis. 4: Average TMRE per group across each time point. 5: Annexin V flow cytometry show increased is independent apoptosis.</p>