A5055665970- Liver Disease Diagnosis and Treatment
- Gene Regulatory Network Analysis
- Liver Diseases and Immunity
- Hepatitis C virus research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Hepatocellular Carcinoma Treatment and Prognosis
- Hepatitis B Virus Studies
- Cardiac tumors and thrombi
- RNA and protein synthesis mechanisms
- Liver Disease and Transplantation
- Systemic Lupus Erythematosus Research
- Diabetes and associated disorders
- Advanced Fluorescence Microscopy Techniques
- Lung Cancer Treatments and Mutations
- Gastroesophageal reflux and treatments
- Monoclonal and Polyclonal Antibodies Research
- Evolution and Genetic Dynamics
- Viral-associated cancers and disorders
- Adrenal Hormones and Disorders
- Bacterial Genetics and Biotechnology
- HIV/AIDS drug development and treatment
- Alcohol Consumption and Health Effects
- Sarcoma Diagnosis and Treatment
- Biosimilars and Bioanalytical Methods
Harvard University
2020-2025
Brigham and Women's Hospital
2022-2025
Massachusetts General Hospital
2019-2025
Mass General Brigham
2023
MGH Institute of Health Professions
2022
Kite (United States)
2016
Washington University in St. Louis
2012-2015
University of Cincinnati
2006
University of Toronto
2000
Ontario Institute for Cancer Research
2000
A major goal in computational biology is to develop models that accurately predict a gene's expression from its surrounding regulatory DNA. Here we present one class of such models, thermodynamic state ensemble models. We describe the biochemical derivation framework simple terms, and lay out mathematical components comprise each model. These include (1) possible states promoter, where defined as particular arrangement transcription factors bound DNA (2) binding constants affinity...
Abstract Background: Immune checkpoint inhibitors (ICIs) to treat cancer have revolutionized immuno-oncology. However, therapy is limited by frequent immune-related adverse events, including immune-mediated liver injury from (ILICI), which occurs in ∼1-17% of patients on anti-PD-1 and/or CTLA-4 therapy. While ILICI often mild, it can cause severe hepatic dysfunction, delay therapy, and require immunosuppressive treatments that may compromise anti-tumor immune responses. shares clinical...
ABSTRACT Glucocorticoid-induced adrenal insufficiency (GIAI) persists for months to years after long-term treatment, which past studies suggest is mediated by initial, post-withdrawal hypothalamic-pituitary suppression. We examined the timing of hypothalamic, pituitary, and (HPA) recovery 8 weeks dexamethasone (DEX) treatment in mice. At withdrawal, HPA function was fully suppressed, but Crh mRNA plasma ACTH surprisingly rebounded above control levels within 1 week. Despite this,...
Stochastic fluctuations in gene expression give rise to distributions of protein levels across cell populations. Despite a mounting number theoretical models explaining stochasticity expression, we lack robust, efficient, assumption-free approach for inferring the molecular mechanisms that underlie shape distributions. Here propose method sets biochemical rate constants govern chromatin modification, transcription, translation, and RNA degradation from expression. We asked whether rates...
Background: Histopathology remains the gold standard for diagnosing and staging metabolic dysfunction–associated steatotic liver disease (MASLD). The feasibility of studying MASLD progression in electronic medical records based on histological features is limited by free-text nature pathology reports. Here we introduce a natural language processing (NLP) algorithm to automatically score histology features. Methods: From Mass General Brigham health care system record, identified all patients...
Cell-to-cell variance in protein levels (noise) is a ubiquitous phenomenon that can increase fitness by generating phenotypic differences within clonal populations of cells. An important challenge to identify the specific molecular events control noise. This task complicated strong dependence protein's cell-to-cell on its mean expression level through power-law like relationship (σ2∝μ1.69). Here, we dissect nature this using stochastic model parameterized with experimentally measured values....
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,...
Alanine (ALT) and aspartate (AST) aminotransferases are standard-of-care biomarkers for liver injury though their temporal dynamics during resolution remain incompletely characterized. Here, we analyze aminotransferase kinetics to determine whether rate laws can be ascertained acute agnostic etiology. From 6.5 million AST ALT measurements in 91,086 patients, identify a single rate-limiting step transaminase decline enabling the discovery of plasma clearance rates (1.13 days
We examined the rates of variant population turnover V1-V2 and V4-V5 hypervariable domains human immunodeficiency virus type 1 (HIV-1) gp120 molecule in longitudinal plasma samples from 14 men with chronic HIV-1 infection using heteroduplex tracking assays (HTA). Six had high CD4+ T-cell loss, eight low loss over 2.5 to 8 years infection. found that env populations changed dramatically time all subjects; changes these regions were significantly correlated each another time. The subjects...
ABSTRACT Myelofibrosis is a hematologic condition that predisposes to the formation of large and small portal venous clots. Portal injury believed underlie mechanism development noncirrhotic hypertension in this population. We describe patient with myelofibrosis, proven hypertension, extramedullary hematopoiesis no imaging or pathologic evidence microvascular macrovascular clot. provide concise review literature which highlights patients myelofibrosis related conditions polycythemia vera...
Background: Liver function tests (LFTs) are elevated in >50% of hospitalized individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increased enzyme levels correlating a more COVID-19 course. Despite these observations, evaluations viral presence within liver parenchyma and impact on remain controversial. Methods Results: Our work is comprehensive immunopathological evaluation tissue from 33 patients severe, ultimately fatal, cases SARS-CoV-2 infection....
Abstract Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) is an essential tool for the detection of cell death in tissues. Although TUNEL not known to be compatible with multiplexed spatial proteomic methods, harmonizing such methods offers opportunity delineate cell-type specific labeling and precise contextualization complex Here we evaluated variations assay their compatibility a immunofluorescence method, multiple iterative by antibody neodeposition (MILAN), two...
Abstract Fibrolamellar carcinoma (FLC) is a rare malignancy disproportionately affecting adolescents and young adults with no standard of care. FLC characterized by thick stroma, which has long suggested an important role the tumor microenvironment. Over past decade, several studies have revealed aberrant markers pathways in FLC. However, significant drawback these efforts that they were conducted on bulk samples. Consequently, identities roles distinct cell types within milieu, patterns...
A 34-year-old man was admitted to the hospital because of dyspnea. An antibody differentiation assay confirmed a diagnosis human immunodeficiency virus type 1 infection, and chest imaging notable for diffuse ground-glass opacities. After treatment Pneumocystis jirovecii pneumonia initiated, acute abdominal pain developed. diagnostic procedure performed.