Hannah R. Watkoske
A5014047829- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- MicroRNA in disease regulation
- Diabetes and associated disorders
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- Pancreatitis Pathology and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immune cells in cancer
- Galectins and Cancer Biology
- Extracellular vesicles in disease
- Renal and related cancers
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Radiomics and Machine Learning in Medical Imaging
- Phagocytosis and Immune Regulation
University of Michigan
2022-2024
Abstract The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from in absence disease and rapid postmortem degradation. We obtained pancreata brain dead donors, thus avoiding any warm ischemia time. 30 donors were diverse age race had no known disease. Histopathologic analysis samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions most individuals irrespective age. Using a combination multiplex IHC, single-cell RNA sequencing,...
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...
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...
Abstract Dysregulation of epigenetic factors is a key component tumorigenesis. BMI1, member the polycomb repressor complex 1 (PRC1), an oncogenic factor studied in many types cancer, including pancreatic ductal adenocarcinoma (PDAC). PDAC third most common cause cancer-related death United States and investigation biology involved transformation critical for improving outcomes this devastating disease. In PDAC, BMI1 required initiation cancer mice enhances vitro growth human murine tumor...
Abstract Study of early pancreas neoplasia in humans had previously been limited by lack available tissue. Recent work our group on deceased donor pancreata identified pancreatic intraepithelial (PanIN) lesions non-diseased organs and defined a transcriptomic signature for the microenvironment these pre-cancerous lesions. Prevalence PanINs healthy human tissue was higher than expected established novel model to expand understanding complex biology precursor Epigenetic changes chromatin...
Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival rate only 13%. PDAC develops from precursor lesions, commonly Intraepithelial Neoplasia (PanIN). Studying PanIN in human patients difficult due to its microscopic nature and lack indication for sampling pancreas absence disease. In collaboration Gift Life - Michigan, local organ tissue donor organization, we obtained over 80 pancreata research. Surprisingly, found vast majority organs,...
<p>Supplementary Figures 11-14 and associated legends.</p>
<div>Abstract<p>The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the in absence disease and rapid postmortem degradation. We obtained pancreata brain dead donors thus avoiding any warm ischemia time. The 30 were diverse age race had no known disease. Histopathological analysis samples revealed PanIN lesions most individuals irrespective age. Using a combination multiplex immunohistochemistry, single cell RNA sequencing,...
<div>Abstract<p>The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the in absence disease and rapid postmortem degradation. We obtained pancreata brain dead donors thus avoiding any warm ischemia time. The 30 were diverse age race had no known disease. Histopathological analysis samples revealed PanIN lesions most individuals irrespective age. Using a combination multiplex immunohistochemistry, single cell RNA sequencing,...
<p>Supplementary Figures 1-10 and associated legends</p>
<p>Supplementary Figures 1-10 and associated legends</p>
<p>Supplementary Figures 11-14 and associated legends.</p>
<p>Supplementary Figures 11-14 and associated legends.</p>
<p>Supplementary Figures 1-10 and associated legends</p>
<p>Supplementary Figures 1-10 and associated legends</p>
<p>Supplementary Figures 11-14 and associated legends.</p>
<div>Abstract<p>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...
<p>Figure S1: IL<sup>-33+</sup> stromal cells are abundant in human and mouse PDA.</p>
<p>Figure S2: Stromal IL-33 promotes PDA growth.</p>
<p>Figure S3: Pancreatic fibroblasts secrete IL-33 in response to oxidative stress.</p>