A5061240871- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Genetic factors in colorectal cancer
- Ferroptosis and cancer prognosis
- Neuroendocrine Tumor Research Advances
- Immune cells in cancer
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Angiogenesis and VEGF in Cancer
- Lung Cancer Treatments and Mutations
- Epigenetics and DNA Methylation
- Chemokine receptors and signaling
- Cancer Immunotherapy and Biomarkers
- Cancer Mechanisms and Therapy
- Single-cell and spatial transcriptomics
- Renal cell carcinoma treatment
- Gene expression and cancer classification
- Cancer, Hypoxia, and Metabolism
- Hepatocellular Carcinoma Treatment and Prognosis
- CRISPR and Genetic Engineering
- Lung Cancer Research Studies
- Immune Cell Function and Interaction
- Lymphatic System and Diseases
Center for Systems Biology
2009-2025
Harvard University
2015-2025
Massachusetts General Hospital
2015-2025
Boston VA Research Institute
2024
MGH Institute of Health Professions
2022
Boston University
2022
Brigham and Women's Hospital
2015-2021
Howard Hughes Medical Institute
2018-2021
Salk Institute for Biological Studies
2019
Haukeland University Hospital
2014
Metastases undergo reconstruction Cancer cells from primary tumors can migrate to regional lymph nodes and distant organs. The prevailing model in oncology is that node metastases give rise metastases. This “sequential progression model” the rationale for surgical removal of tumor-draining nodes. Naxerova et al. used phylogenetic methods reconstruct evolutionary relationship tumors, metastases, 17 patients with colorectal cancer (see Perspective by Markowitz). sequential applied only...
Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac aging heart failure with preserved ejection fraction, remain unclear. Here we show that macrophages expand humans mice which was induced by either hypertension advanced age. A higher murine myocardial macrophage density results from monocyte recruitment increased hematopoiesis bone marrow spleen....
Although the role of TGF-β in tumor progression has been studied extensively, its impact on drug delivery tumors remains far from understood. In this study, we examined effect blockade and efficacy conventional therapeutics nanotherapeutics orthotopic mammary carcinoma mouse models. We used both genetic (overexpression sTβRII, a soluble type II receptor) pharmacologic (1D11, neutralizing antibody) approaches to block signaling. two models (human MDA-MB-231 murine 4T1 cell lines),...
Following myocardial infarction (MI), myeloid cells derived from the hematopoietic system drive a sharp increase in systemic leukocyte levels that correlates closely with mortality. The origin of these cells, and response stem progenitor (HSPCs) to MI, however, is unclear. Here, we identify CCR2+CD150+CD48− LSK subset as most upstream contributor emergency myelopoiesis after ischemic organ injury. This has 4-fold higher proliferation rates than CCR2−CD150+CD48− displays differentiation bias,...
Cancer-associated fibroblasts (CAFs) can either suppress or support T lymphocyte activity, suggesting that CAFs may be reprogrammable to an immunosupportive state. Angiotensin receptor blockers (ARBs) convert myofibroblast a quiescent state, but whether ARBs reprogram promote activity and enhance immunotherapy is unknown. Moreover, ARB doses are limited by systemic adverse effects such as hypotension due the importance of angiotensin signaling outside tumors. To efficacy specificity in...
Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune stromal cells contribute atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte
Whole chromosome and arm-level copy number alterations occur at high frequencies in tumors, but their selective advantages, if any, are poorly understood. Here, utilizing unbiased whole genetic screens combined with vitro evolution to generate arm- subarm-level events, we iteratively selected the fittest karyotypes from aneuploidized human renal mammary epithelial cells. Proliferation-based karyotype selection these lines modeled tissue-specific tumor aneuploidy patterns patient cohorts...
The brain microenvironment triggers HER3-dependent de novo resistance to therapies targeting PI3K or HER2 in HER2-positive and/or PIK3CA -mutant breast cancer cells.
Purpose: Angiotensin system inhibitors (ASI) can improve prognosis in multiple cancer types, including pancreatic ductal adenocarcinoma (PDAC). However, no study has examined the effect of ASIs alone or combined with adjuvant chemotherapy resected PDAC patients.Experimental Design: We performed an analysis records ASI users and nonuser patients seen at Massachusetts General Hospital (Boston, MA) between January 2006 December 2010. To identify mechanisms PDAC, we RNA sequencing (RNA-Seq)...
Abnormal hematopoiesis advances cardiovascular disease by generating excess inflammatory leukocytes that attack the arteries and heart. The bone marrow niche regulates hematopoietic stem cell proliferation hence systemic leukocyte pool, but whether affects organ's microvasculature is unknown. Here we show hypertension, atherosclerosis myocardial infarction (MI) instigate endothelial dysfunction, leakage, vascular fibrosis angiogenesis in marrow, altogether leading to overproduction of...
A sleepless night may feel awful in its aftermath, but sleep's revitalizing powers are substantial, perpetuating the idea that convalescent sleep is a consequence-free physiological reset. Although recent studies have shown catch-up insufficiently neutralizes negative effects of debt, mechanisms control prolonged disruption not understood. Here, we show interruption restructures epigenome hematopoietic stem and progenitor cells (HSPCs) increases their proliferation, thus reducing clonal...
Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, CD8 + T cell blocking studies mice, demonstrated this results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment disrupts the blood–tumor barrier. Used lieu of immunosuppressive corticosteroids, angiotensin receptor blocker...
Significance Malignant breast tumors consist of supporting stromal cells and epithelial cancerous cells. The cancer cell population is fueled by a reservoir tumor-initiating cells, these can give rise to the bulk tumor. Some populations with vast proliferative potential may be intrinsically resistant standard anticancer therapy. This intrinsic resistance partially explain limitations therapies in curing patients suggest reason for relapse. In this study, we demonstrate that loss...