A5027836515- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Liver physiology and pathology
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- Immunotherapy and Immune Responses
- Radiopharmaceutical Chemistry and Applications
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Genetic and Kidney Cyst Diseases
- Liver Disease Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Ferroptosis and cancer prognosis
- Breast Cancer Treatment Studies
- Advanced Breast Cancer Therapies
- Ethics in Business and Education
- Cancer Diagnosis and Treatment
Northeastern University
2025
The University of Texas Southwestern Medical Center
2021-2024
Southwestern Medical Center
2022-2024
Harold C. Simmons Comprehensive Cancer Center
2023
Karolinska Institutet
2023
University of California, Irvine
2022
University of Baltimore
2020-2021
Johns Hopkins University
2018-2021
Sidney Kimmel Comprehensive Cancer Center
2017-2021
Hong Kong Baptist University
2019-2021
<h3>Objective</h3> Immune responses are important in dictating non-alcoholic steatohepatitis (NASH) outcome. We previously reported that upregulation of hedgehog (Hh) and osteopontin (OPN) occurs NASH, Hh-regulated accumulation natural killer T (NKT) cells promotes hepatic stellate cell (HSC) activation, cirrhotic livers harbour large numbers NKT cells. <h3>Design</h3> The hypothesis activated drive fibrogenesis during NASH was evaluated by assessing if depletion protects against fibrosis;...
We present an integrated single-cell RNA sequencing atlas of the primary breast tumor microenvironment (TME) containing 236,363 cells from 119 biopsy samples across eight datasets. In this study, we leverage resource for multiple analyses immune and cancer epithelial cell heterogeneity. define natural killer (NK) heterogeneity through six subsets in TME. Because NK correlates with heterogeneity, characterize at level single-gene expression, molecular subtype, 10 categories reflecting...
Objective Chronic fibrosing liver injury is a major risk factor for hepatocarcinogenesis in humans. Mice with targeted deletion of Mdr2 (the murine ortholog MDR3) develop chronic injury. Hepatocellular carcinoma (HCC) emerges spontaneously such mice by 50–60 weeks age, providing model fibrosis-associated hepatocarcinogenesis. We used Mdr2−/− to investigate the hypothesis that activation hedgehog (Hh) signaling pathway promotes development both fibrosis and HCC. Methods Hepatic fibrosis, Hh...
Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer escape NK cell surveillance. Using ex vivo in models of metastasis, we establish that keratin-14+ breast are vulnerable to cells. We then discovered exposure causes lose their cytotoxic ability promote metastatic outgrowth. Gene expression comparisons revealed healthy an active molecular phenotype, whereas tumor-exposed (teNK) resemble resting Receptor–ligand analysis between...
<h3>Objective</h3> Vascular remodelling during liver damage involves loss of healthy sinusoidal endothelial cell (LSEC) phenotype via capillarisation. Hedgehog (Hh) signalling regulates vascular development and increases injury. This study therefore examined its role in <h3>Design</h3> Primary LSEC were cultured for 5 days to induce Pharmacological, antibody-mediated genetic approaches used manipulate Hh signalling. Effects on mRNA protein expression Hh-regulated genes capillarisation...
Schistosomiasis mansoni is a major cause of portal fibrosis and hypertension. The Hedgehog pathway regulates fibrogenic repair in some types liver injury.Determine if activation occurs during progression schistosomiasis to determine macrophage-related mechanisms are involved.Immunohistochemistry was used characterize the cells that generate respond ligands 28 biopsies from patients with different grades staged by ultrasound. Cultured macrophages (RAW264.7 primary rat Kupffer cells)...
Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role Hh-dependent myofibroblasts hepatocarcinogenesis is unknown. Here, we used human HCC samples, mouse model, hepatoma cell/myofibroblast cocultures to examine hypothesis modulates myofibroblasts'...
Schistosomiasis is a major cause of portal hypertension worldwide. It associates with fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated hypothesis schistosome eggs release factors directly stimulate liver cells to produce osteopontin (OPN), pro-fibrogenic protein stimulates hepatic stellate become myofibroblasts. also investigated utility OPN as biomarker and/or severity hypertension. Cultured...
To prevent damage to the host or its commensal microbiota, epithelial tissues must match intensity of immune response severity a biological threat. Toll-like receptors allow cells identify microbe associated molecular patterns. However, mechanisms that mitigate noise in single ensure quantitatively appropriate responses remain unclear. Here we address this question using cell and molecule approaches mammary primary organoids. We find respond bacterial patterns by activating subset an...
Fast volumetric imaging of large fluorescent samples with high-resolution is required for many biological applications. Oblique plane microscopy (OPM) provides high spatiotemporal resolution, but the field view typically limited by its optical train and pixel number camera. Mechanically scanning sample or decreasing overall magnification system can partially address this challenge, albeit reducing speed spatial respectively. Here, we introduce a novel dual-axis scan unit OPM that facilitates...
Background Alcohol consumption promotes hepatocellular carcinoma ( HCC ). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol hepatotoxic, habitual ingestion evokes recurrent hepatic alcohol‐preferring P ) rat model mimics the level of humans who habitually abuse alcohol. Previously, we showed heavy amplified age‐related hepatocarcinogenesis in rats, over 80%...
Abstract Purpose Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these along with characterization of the microenvironment (TME) between tumors (BrTs), axillary metastases (AxMs), liver (LvMs), non-axillary lymph node metastases, non-liver to determine differences related site metastatic disease. Methods 3076 unpaired biopsies...
Abstract Background: Breast cancer is a complex disease characterized by heterogeneity, and the analysis of circulating tumor DNA (ctDNA) holds promise for capturing this heterogeneity. Recently, ctDNA testing has been employed in clinical practice to guide targeted therapies metastatic breast cancer, particularly cases hormone receptor-positive with mutations PIK3CA ESR1. This approach becomes necessary when traditional biopsies are inadequate next-generation sequencing (NGS) or fail...
Metastatic disease results from the dissemination of tumor cells beyond their organ origin to grow in distant organs and is primary cause death patients with advanced breast cancer. Preclinical murine models which tumors spontaneously metastasize are valuable tools for studying metastatic progression novel cancer treatment combinations. Here, we characterize a syngeneic cell line that provides model neu-expressing quicker onset widespread metastases after orthotopic mammary implantation...
Breast cancer metastases exhibit many different genetic alterations, including copy number amplifications (CNA). CNA are alterations that increasingly becoming relevant to breast oncology clinical practice. Here we identify in metastatic tumor samples using publicly available datasets and characterize their expression function a mouse model of cancer. Our findings demonstrate our organoid generation can be implemented study clinically features reflect the heterogeneity individual tumors.
572 Background: Endocrine therapy (ET) reduces mortality in hormonally driven breast cancer (BC). The impacts of ET on the estrogen receptor are well known; however, there is limited data impact host's immune system. This project aims to elucidate potential immunomodulatory effects ET-induced deprivation HR+/HER2 negative early-stage patients (pts) as baseline differences between BC pts and healthy controls (HC). Methods: Pts with Stage I-III HR+/HER2- initiating after completion local...
The poor prognosis of pancreatic cancer patients using currently available therapies mandates novel therapeutics that combine anti-neoplastic potency with toxicity-minimizing specificity. Employing an overlapping pathway screen to identify genes exhibiting coordinated expression as a consequence terminal cell differentiation and replicative senescence, we identified human polynucleotide phosphorylase (hPNPase(old-35)), 3',5'-exoribonuclease exhibits robust growth-suppressing effects in wide...