A5016242807- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Lipoproteins and Cardiovascular Health
- IL-33, ST2, and ILC Pathways
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Macrophage Migration Inhibitory Factor
- Diabetes and associated disorders
- Fibroblast Growth Factor Research
- Cancer Cells and Metastasis
- Adenosine and Purinergic Signaling
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Nuclear Receptors and Signaling
- Pancreatic function and diabetes
- Extracellular vesicles in disease
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Signaling Pathways in Disease
- Calcium signaling and nucleotide metabolism
University of Michigan
2019-2025
Michigan United
2022
California State University, Long Beach
2011
Abstract Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to immunosuppressive microenvironment, we depleted Tregs a model of Contrary our expectations, Treg depletion failed relieve immunosuppression led accelerated tumor progression. We show that key source TGFβ ligands and, accordingly, their reprogramed fibroblast population, with loss tumor-restraining, smooth muscle actin–expressing fibroblasts. Conversely, observed an increase...
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with few effective therapeutic options. PDAC characterized by an extensive fibroinflammatory stroma that includes abundant infiltrating immune cells. Tumor-associated macrophages (TAM) are prevalent within the and key drivers of immunosuppression. TAMs in human murine elevated expression apolipoprotein E (ApoE), mediates cholesterol metabolism has known roles cardiovascular Alzheimer's disease but no role PDAC. We report here...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy 1,2 . This mediated in part by complex tumour microenvironment 3 , low vascularity 4 and metabolic aberrations 5,6 Although altered metabolism drives progression, the spectrum of metabolites used as nutrients PDA remains largely unknown. Here we identified uridine fuel for glucose-deprived conditions assessing how more than 175 impacted activity 21 pancreatic cell lines under nutrient...
An extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it well appreciated that are immunosuppressive and contribute to the poor response immunotherapy; however, mechanisms immune suppression complex not fully understood. Immunosuppressive classically defined by expression enzyme Arginase 1 (ARG1), which we demonstrated potently expressed tumor-associated from both human patients mouse models. While routinely used as polarization...
Pancreatic ductal adenocarcinoma (PDA) is associated with activation of WNT signaling. Whether this signaling pathway regulates the tumor microenvironment has remained unexplored. Through single-cell RNA sequencing human pancreatic cancer, we discovered that tumor-infiltrating CD4+ T cells express TCF7, encoding for transcription factor TCF1. We conditionally inactivated Tcf7 in CD4 expressing a mouse model cancer and observed changes immune microenvironment, including more CD8+ fewer...
Nutrient stress in the tumor microenvironment requires cancer cells to adopt adaptive metabolic programs for survival and proliferation. Therefore, knowledge of microenvironmental nutrient levels how cope with such nutrition is critical understand metabolism underpinning cell biology. Previously, we performed quantitative metabolomics interstitial fluid (the local perfusate) murine pancreatic ductal adenocarcinoma (PDAC) tumors comprehensively characterize availability these tumors. Here, develop
Abstract Pancreatic cancer is characterized by an extensive fibroinflammatory microenvironment. During carcinogenesis, normal stromal cells are converted to cytokine-high cancer-associated fibroblasts (CAF). The mechanisms underlying this conversion, including the regulation and function of fibroblast-derived cytokines, poorly understood. Thus, efforts therapeutically target CAFs have so far failed. Herein, we show that signals from epithelial expressing oncogenic KRAS—a hallmark pancreatic...
Proper Hedgehog (HH) signaling is essential for embryonic development, while aberrant HH drives pediatric and adult cancers. frequently dysregulated in pancreatic cancer, yet its role remains controversial, with both tumor-promoting tumor-restraining functions reported. Notably, the GLI family of transcription factors (GLI1, GLI2, GLI3), remain largely unexplored cancer. We therefore investigated individual combined contributions GLI1-3 to cancer progression. At pre-cancerous stages,...
Abstract Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed high rate early metastasis and low efficacy current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies our group others shown that tumor-associated macrophages (TAM) are instrumental in maintaining immunosuppression PDA. Here, we explored the role Notch signaling, key regulator immune response,...
Pancreatic ductal adenocarcinoma (PDAC) is a drug resistant and lethal cancer. Identification of the genes that consistently show altered expression across patients' cohorts can expose effective therapeutic targets strategies. To identify such genes, we separately analyzed five human PDAC microarray datasets. We defined as 'consistent' if upregulated or downregulated in ≥ 4 datasets (adjusted P<0.05). The were subsequently queried additional datasets, including single-cell RNA-sequencing...
Vacuoles of yeast Saccharomyces cerevisiae are functionally analogous to mammalian lysosomes. Both cellular organelles responsible for macromolecular degradation, ion/pH homeostasis, and stress survival. We hypothesized that undefined gene functions remain at post-endosomal stage vacuolar events performed a genome-wide screen directed such the late endosome vacuole interface – ENV genes. The immunodetection was designed identify mutants internally accumulate precursor form hydrolase...
Abstract An extensive fibroinflammatory stroma rich in macrophages is a hallmark of pancreatic cancer. In this disease, it well appreciated that are immunosuppressive and contribute to the poor response immunotherapy; however, mechanisms immune suppression complex not fully understood. Immunosuppressive classically defined by expression enzyme Arginase 1 (Arg1), which we demonstrated potently expressed tumor associated from both human patients mouse models. While routinely used as...
Pancreatic ductal adenocarcinoma (PDA) continues to have a dismal prognosis. The poor survival of patients with PDA has been attributed high rate early metastasis and low efficacy current therapies, which partly result from its complex immunosuppressive tumor microenvironment. Previous studies our group others shown that tumor-associated macrophages (TAMs) are instrumental in maintaining immunosuppression PDA. Here, we explored the role Notch signaling, key regulator immune response, within...
Abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal disease characterized by high invasiveness, therapeutic resistance, and metabolic aberrations. Although altered metabolism drives PDA growth survival, the complete spectrum of metabolites used as nutrients remains largely unknown. Here, we aimed to determine novel utilized PDA. We assessed how >175 impacted activity in 19 cell lines under nutrient-restricted conditions. This analysis identified uridine metabolite driver survival...
<p>Notch activation detected in C57BL/6J:CBF:H2B-Venus mouse pancreatic orthotopic tumor.</p>
<p>Notch activation in the tumor microenvironment of human PDA.</p>
<p>γ-secretase inhibitor treatment reduces expression of HES1 in vivo.</p>
<p>γ-secretase inhibitor treatment reduces expression of HES1 in vivo.</p>
<p>Notch activation detected in C57BL/6J:CBF:H2B-Venus mouse pancreatic orthotopic tumor.</p>
<p>Notch activation detected in C57BL/6J:CBF:H2B-Venus mouse pancreas and tumor microenvironment of spontaneous PanIN lesions.</p>
<p>Primer sequences for quantitative RT-PCR</p>
<p>Notch activation detected in C57BL/6J:CBF:H2B-Venus mouse pancreas and tumor microenvironment of spontaneous PanIN lesions.</p>
<p>Notch activation in the tumor microenvironment of human PDA.</p>