A5022822292- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- COVID-19 Clinical Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Immune cells in cancer
- Cancer Research and Treatments
- Ocular Surface and Contact Lens
- RNA Research and Splicing
- Radiomics and Machine Learning in Medical Imaging
- Immune responses and vaccinations
- vaccines and immunoinformatics approaches
- Antimicrobial Peptides and Activities
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- Salivary Gland Disorders and Functions
- Long-Term Effects of COVID-19
- Molecular Biology Techniques and Applications
- Cancer-related molecular mechanisms research
- Pancreatic and Hepatic Oncology Research
Massachusetts General Hospital
2021-2024
Broad Institute
2021-2023
Center for Cancer Research
2021-2022
Harvard University
2021
Boston University
2018
Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs disease outcome, we focused on tumor-to-tumor variation to examine 52 head neck squamous cell carcinomas. We found macrophage polarity-defined by
Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls perform bulk RNA sequencing enriched neutrophils, plasma proteomics, high-throughput antibody profiling to investigate relationships between states severity. We identify dynamic switches six distinct subtypes. At days 3 7 post-hospitalization, with display a granulocytic...
Immune checkpoint blockade (CPB) improves melanoma outcomes, but many patients still do not respond. Tumor mutational burden (TMB) and tumor-infiltrating T cells are associated with response, integrative models improve survival prediction. However, integrating immune/tumor-intrinsic features using data from a single assay (DNA/RNA) remains underexplored. Here, we analyze whole-exome bulk RNA sequencing of tumors new published cohorts 189 178 receiving CPB, respectively. Using DNA, calculate...
Abstract Alternative splicing is a core biological process that enables profound and essential diversification of gene function. Short-read RNA sequencing approaches fail to resolve isoforms therefore primarily enable expression measurements - an isoform unaware representation the transcriptome. Conversely, full-length using long-read technologies are able capture complete transcript isoforms, but their utility deeply constrained due throughput limitations. Here, we introduce MAS-ISO-seq,...
Many cancer patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses. Circulating biomarkers the potential to identify primary resistance or early progression on therapy alter course and avoid unnecessary toxicity. Unbiased multimodal proteomic profiling in blood has been underexplored due previously limited scalability of multiplexing technologies cohorts lacking time-series sampling. To address this, we performed plasma >2,900 proteins...
The risk of developing lymphoma in patients with Sjögren’s syndrome (SS) is 44 times higher than the normal population most common lymphomas derived from marginal zone B (MZB) cells. Current understanding role MZB cells SS primarily based on salivary gland pathology, while their contextual association lacrimal glands and ocular manifestations largely remains unknown. We examined this possibility using a mouse model (thrombospondin-1 deficient (TSP1−/−)) well-characterized disease. determined...
Abstract Introduction: Efforts to overcome resistance immune checkpoint inhibition (ICI) are paramount, and novel combination strategies in development. Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment that has demonstrated modulatory effects. We hypothesized may prime the tumor microenvironment (TME) through direct modulation of tumor, thereby generating anti-tumor response ICI refractory tumors. Methods: In this non-randomized phase II...
Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. We hypothesized that may modify the immune microenvironment through direct modulation of tumor, thereby generating anti-tumor response in tumors refractory to checkpoint inhibition (ICI). In this non-randomized phase II single-center study (NCT03290677), subjects with unresectable melanoma progressing on ICI underwent enlarging metastasis, and was continued for a minimum two additional cycles....
Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized + patients, 78 âˆ' acute respiratory distress syndrome 8 healthy controls, performed bulk RNA-sequencing enriched neutrophils, plasma proteomics, cfDNA measurements high throughput antibody profiling assays to investigate relationship neutrophil states...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with few effective treatment options. It characterized by highly desmoplastic tumor microenvironment and paucity of dendritic cells, leading to low immune cell infiltration poor outcomes immunotherapy treatments that are in other cancers. In recent pilot study, metastatic PDAC patients who had progressed on chemotherapy were treated combination dual checkpoint blockade (ICB) therapy radiation which resulted an 18% overall...
Purpose: The efficacy of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in large B-cell lymphoma (LBCL) patients is limited by acute toxicities, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS). Previous biomarker studies have been constrained narrow protein panels time points. We employed NULISATM, a novel ultrasensitive assay capable simultaneously quantifying 204 proteins, to identify temporal proteome associations with...
e21503 Background: Melanoma therapy has been revolutionized by two novel therapeutic approaches: mitogen activated protein kinase (MAPK) targeted (MTT) and immune checkpoint blockade (ICB). It shown that MTT enhances anti-tumor immunity within the tumor microenviroment (TME), thus providing a strong rationale for its combination with immunotherapy. Regimens combining ICB there have had mixed results, which patients (pts) should be treated these combinations is unknown. Methods: 16 pts...
Cancer immunotherapy with checkpoint blockade (CPB) leads to improved outcomes in melanoma and other tumor types, but a majority of patients do not respond. High mutation burden (TMB) high levels tumor-infiltrating T cells have been associated response immunotherapy, integrative models predict clinical benefit using DNA or RNA alone comprehensively explored. We sequenced from receiving CPB, aggregated previously published data, yielding whole exome sequencing data for 189 bulk 178 patients....
9522 Background: Melanoma therapy has been revolutionized by two novel therapeutic approaches: mitogen activated protein kinase (MAPK) targeted (MTT) and immune checkpoint blockade (ICB). Less than half of patients respond to ICB monotherapy, in part due non-responsive tumor microenvironment (TME). It previously shown that MTT enhances anti-tumor immunity within the TME, thus providing a strong rationale for its combination with immunotherapy. Regimens combining have had mixed results, which...
Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized + patients, 78 - acute respiratory distress syndrome 8 healthy controls, performed bulk RNA-sequencing enriched neutrophils, plasma proteomics, cfDNA measurements high throughput antibody profiling assays to investigate relationship neutrophil states...
Abstract Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers but been ineffective for microsatellite stable (MSS) PDAC. The lack efficacy immunotherapies in PDAC is due to: 1) a desmoplastic tumor microenvironment (TME); 2) presence suppressive cells, including myeloid derived suppressor cells and regulatory T cells; 3) antigen-presenting dendritic (DCs) that are important priming an effective immune response to generate functionally antigen-specific cells. We...