A5019314486- Liver Disease Diagnosis and Treatment
- Alcohol Consumption and Health Effects
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- Immune cells in cancer
- Amino Acid Enzymes and Metabolism
- CAR-T cell therapy research
- RNA modifications and cancer
- Diabetes and associated disorders
- Liver Disease and Transplantation
- Immune Cell Function and Interaction
- PI3K/AKT/mTOR signaling in cancer
- Heme Oxygenase-1 and Carbon Monoxide
- Inflammasome and immune disorders
- Diet, Metabolism, and Disease
- Chronic Lymphocytic Leukemia Research
- Cancer, Hypoxia, and Metabolism
Beth Israel Deaconess Medical Center
2022-2024
Harvard University
2022-2024
Massachusetts Institute of Technology
2020-2023
IIT@MIT
2022
Metabolism is a fundamental process for all cellular functions. For decades, there has been growing evidence of relationship between metabolism and malignant cell proliferation. Unlike normal differentiated cells, cancer cells have reprogrammed in order to fulfill their energy requirements. These display crucial modifications many metabolic pathways, such as glycolysis glutaminolysis, which include the tricarboxylic acid (TCA) cycle, electron transport chain (ETC), pentose phosphate pathway...
Objective Alcohol use in metabolic dysfunction-associated steatohepatitis (MASH) is associated with an increased risk of fibrosis and liver-related death. Here, we aimed to identify a mechanism through which repeated alcohol binges exacerbate liver injury high fat-cholesterol-sugar diet (MASH diet)-induced model MASH. Design C57BL/6 mice received either chow or the MASH for 3 months without weekly binges. Neutrophil infiltration, neutrophil extracellular traps (NETs) were evaluated. Results...
Background: The recent increase in the incidence of alcohol-associated hepatitis (AH) coincides with obesity epidemic United States. However, current mouse models do not fully replicate combined insults obesity, metabolic dysfunction–associated steatohepatitis, and alcohol. aim this study was to develop a new model that recapitulates robust inflammatory fibrotic phenotype characteristic human MetALD. Methods: Eight- 10-week-old male C57BL/6 mice were fed chow or high fat-cholesterol-sugar...
Background & Aims: Prolonged systemic inflammation contributes to poor clinical outcomes in severe alcohol-associated hepatitis (AH) even after the cessation of alcohol use. However, mechanisms leading this persistent remain be understood. Approach Results: We show that while chronic induces nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation liver, binge results not only NLRP3 but also increased circulating...
Cancer immunotherapies, in particular checkpoint blockade immunotherapy (CBT), can induce control of cancer growth, with a fraction patients experiencing durable responses. However, the majority currently do not respond to CBT and molecular determinants resistance have been fully elucidated. Mounting clinical evidence suggests that clonal status neoantigens (NeoAg) impacts anti-tumor T cell response. High intratumor heterogeneity (ITH), where NeoAgs are expressed subclonally, is correlated...
Massive inflammation and liver failure are main contributors to the high mortality in alcohol-associated hepatitis (AH). In recent clinical trials, granulocyte colony-stimulating factor (G-CSF) therapy improved function survival patients with AH. However, mechanisms of G-CSF-mediated beneficial effects AH remain elusive. this study, we evaluated vivo G-CSF administration, using a mouse model treatment significantly reduced damage alcohol-fed mice even though it increased numbers...
Abstract Background & Aims Various intracellular pathways regulate inflammation in NASH. Cyclic GMP‐AMP synthase (cGAS) is a DNA sensor that activates STING and plays role inflammatory diseases. Here, we explored the of cGAS hepatic damage, steatosis, inflammation, liver fibrosis mouse models Methods deficient (cGAS‐KO) (STING‐KO) mice received high fat‐high cholesterol‐high sugar diet (HF‐HC‐HSD) or relevant control diets. Livers were evaluated after 16 30 weeks. Results HF‐HC‐HSD diet,...
Severe alcohol-associated hepatitis (AH) is a life-threatening form of liver disease. Liver neutrophil infiltration hallmark AH, yet the effects alcohol on functions remain elusive. Identifying therapeutic targets to reduce neutrophil-mediated damage essential. Bruton’s tyrosine kinase (BTK) plays an important role in development and function; however, BTK AH unknown. Using RNA sequencing circulating neutrophils, we found increase Btk expression ( P = 0.05) phosphorylated (pBTK) patients...
<h3>Background</h3> Many cancer immunotherapies depend on the ability of cytotoxic CD8+ T cells to recognize neoantigens MHCI complexes effectively eliminate tumor cells. However, patient response following immunotherapy is highly variable, with recent work suggesting that neoantigen expression patterns can impair response. Specifically, it was observed immune dampened when are expressed only by a subset (heterogeneous expression).<sup>1</sup> To study why anti-tumor immunity reduced in...
<h3>Background</h3> Intra-tumoral heterogeneity (ITH) can limit effective anti-tumor immune responses despite the presence of immunogenic neoantigens. Yet, there is little mechanistic insight into how ITH blunts T cell or clonal and sub-clonal neoantigens define immunologically unfavorable neoantigen architectures, preventing rational design neoantigen-targeting immunotherapy approaches for heterogenous tumors. <h3>Methods</h3> Using lentiviral transduction, we expressed single multiple with...
Abstract Cancer immunotherapies, in particular checkpoint blockade immunotherapy (CBT), can induce control of cancer growth, with a fraction patients experiencing durable responses. However, the majority currently do not respond to CBT and molecular determinants resistance have been fully elucidated. Mounting clinical evidence suggests that clonal status neoantigens (NeoAg) impacts anti-tumor T cell response. High intratumor heterogeneity (ITH), where NeoAgs are expressed subclonally, is...