A5080881712- Genomics and Chromatin Dynamics
- Sarcoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Chromatin Remodeling and Cancer
- Cancer Cells and Metastasis
- Renal and related cancers
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Renal cell carcinoma treatment
- Virus-based gene therapy research
- Cancer, Stress, Anesthesia, and Immune Response
- Immunotherapy and Immune Responses
- interferon and immune responses
- Lymphoma Diagnosis and Treatment
- RNA Research and Splicing
- Immune Cell Function and Interaction
- Cervical Cancer and HPV Research
- RNA modifications and cancer
- MicroRNA in disease regulation
- Cutaneous lymphoproliferative disorders research
- Viral-associated cancers and disorders
- Cancer Treatment and Pharmacology
Harvard University
2017-2024
Massachusetts General Hospital
2017-2024
Center for Cancer Research
2017-2022
University of Massachusetts Chan Medical School
2020
Cancer immunology research is largely focused on the role of cytotoxic immune responses against advanced cancers. Herein, we demonstrate that CD4+ T helper (Th2) cells directly block spontaneous breast carcinogenesis by inducing terminal differentiation cancer cells. Th2 cell immunity, stimulated thymic stromal lymphopoietin, caused epigenetic reprogramming tumor cells, activating mammary gland and suppressing epithelial–mesenchymal transition. polarization was required for this...
Abstract Oncogenic fusion proteins generated by chromosomal translocations play major roles in cancer. Among them, fusions between EWSR1 and transcription factors generate oncogenes with powerful chromatin regulatory activities, capable of establishing complex gene expression programs permissive precursor cells. Here we define the epigenetic 3D connectivity landscape Clear Cell Sarcoma, an aggressive cancer driven EWSR1-ATF1 gene. We find that displays a distinct DNA binding pattern requires...
Medulloblastoma is the most frequent malignant pediatric brain tumor and divided into at least four subgroups known as WNT, SHH, Group 3, 4. Here, we characterized gene regulation mechanisms in aggressive subtype, 3 tumors, through genome-wide chromatin expression profiling. Our results show that active distal sites these tumors are occupied by transcription factor OTX2. Highly OTX2-bound enhancers often arranged clusters of adjacent peaks also bound NEUROD1. These responsive to OTX2 NEUROD1...
Synovial sarcoma (SyS) is an aggressive mesenchymal malignancy invariably associated with the chromosomal translocation t(X:18; p11:q11), which results in in-frame fusion of BAF complex gene SS18 to one three SSX genes. Fusion generates aberrant transcriptional regulator, which, permissive cells, drives tumor development by initiating major chromatin remodeling events that disrupt balance between BAF-mediated activation and polycomb-dependent repression. Here, we developed SyS organoids...
EWS fusion oncoproteins underlie several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive cancer driven by EWS-WT1 proteins. Here we combine chromatin occupancy and 3D profiles to identify EWS-WT1-dependent gene regulation networks target genes. We show that is a powerful activator controlling oncogenic expression program characterizes primary tumors. Similar wild type WT1, has two isoforms differ in their DNA binding domain find they have distinct are...
Cutaneous B-cell lymphomas (CBCL) are rare heterogeneous neoplastic diseases composing about 22.5% of all cutaneous lymphomas. These can be divided into primary and secondary variants with lymphoma (PCBCL) three distinct entities including marginal zone lymphoma, follicle center diffuse large leg type (PCDLBCL, LT). Secondary (CDLBCL) PCDLBCL, LT more aggressive neoplasms compared to the aforementioned CBCL survival rates 37% 50% after 5 years, respectively. CDLBCL present as or subcutaneous...
Abstract Alterations in transcriptional regulators can orchestrate oncogenic gene expression programs cancer. Here we show that the BAF chromatin-remodeling complex, which is mutated over 20% of human tumors, interacts with EWSR1, a member family proteins prion-like domains (PrLD) are frequent partners fusions transcription factors. In Ewing sarcoma, find complex recruited by EWS-FLI1 fusion protein to tumor-specific enhancers and contributes target activation. This process neomorphic...
New immune-based strategies for cancer treatment including the activation of tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs) have led to effective therapeutics against late-stage disease. However, function immune system in combating early-stage cancers remains uncertain. To establish a mechanism that activates cells early carcinogenesis, we studied role an epithelial-derived cytokine, thymic stromal lymphopoietin (TSLP), stages breast development. We previously discovered TSLP blocks...
Abstract New immune-based strategies for cancer treatment including the activation of tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs) have led to effective therapeutics against late-stage disease. However, function immune system in combating early-stage cancers remains uncertain. To establish a mechanism that activates cells early carcinogenesis, we studied role an epithelial-derived cytokine, thymic stromal lymphopoietin (TSLP), stages breast development. We previously discovered...