A5083158901- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Genomics and Diagnostics
- Cancer, Stress, Anesthesia, and Immune Response
- Single-cell and spatial transcriptomics
- Liver Disease Diagnosis and Treatment
- Lymphoma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Extracellular vesicles in disease
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- FOXO transcription factor regulation
- Immunodeficiency and Autoimmune Disorders
Broad Institute
2022-2025
Massachusetts Institute of Technology
2022-2024
Koch Institute for Integrative Cancer Research At MIT
2023
Harvard–MIT Division of Health Sciences and Technology
2023
Harvard University
2022-2023
Ragon Institute of MGH, MIT and Harvard
2023
Allen Institute
2023
Imidazoquinolines (IMDs), such as resiquimod (R848), are of great interest potential cancer immunotherapies because their ability to activate Toll-like receptor 7 (TLR7) and/or TLR8 on innate immune cells. Nevertheless, intravenous administration IMDs causes severe immune-related toxicities, and attempts improve tissue-selective exposure while minimizing acute systemic inflammation have proven difficult. Here, using a library R848 "bottlebrush prodrugs" (BPDs) that differ only by release...
Gliomas are incurable malignancies notable for having an immunosuppressive microenvironment with abundant myeloid cells, the immunomodulatory phenotypes of which remain poorly defined1. Here we systematically investigate these by integrating single-cell RNA sequencing, chromatin accessibility, spatial transcriptomics and glioma organoid explant systems. We discovered four expression programs: microglial inflammatory scavenger programs, both unique to primary brain tumours, systemic...
Gliomas are incurable malignancies notable for an immunosuppressive microenvironment with abundant myeloid cells whose immunomodulatory properties remain poorly defined. Here, utilizing scRNA-seq data 183,062 from 85 human tumors, we discover that nearly all glioma-associated express at least one of four activity programs: Scavenger Immunosuppressive, C1Q CXCR4 Inflammatory, and IL1B Inflammatory. All programs present in IDH1 mutant wild-type gliomas expressed macrophages, monocytes,...
Under chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural immune to perform crucial metabolic, synthetic, detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations surviving their functional repercussions remain unclear. Namely,...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with few effective therapies. Contributing to the complexity of this deadly cancer, PDAC tumors similar genomic backgrounds can express divergent transcriptional programs clinical importance. These subtypes, termed “cell states”, have prognostic significance: in “classical state” generally better outcomes and are thought be more responsive chemotherapy while those “basal aggressive. Currently, cell state not used...
Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with few effective treatments. Even the advent of mutationally-directed therapies targeting KRAS oncogene, PDAC transcriptional plasticity major mechanism therapeutic resistance. As result, there is desperate need to develop additional strategies treat this disease. In addition canonical genomic alterations in KRAS, TP53, CDKN2A, and SMAD4, tumors exhibit diverse programs, or "cell states," prognostic implications:...