Samantha B. Kemp
A5058464154- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Radiomics and Machine Learning in Medical Imaging
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Chemokine receptors and signaling
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Hedgehog Signaling Pathway Studies
- Cancer Cells and Metastasis
- Lipoproteins and Cardiovascular Health
- Nanoparticle-Based Drug Delivery
- Biochemical and Molecular Research
- Macrophage Migration Inhibitory Factor
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Cancer, Hypoxia, and Metabolism
- Fibroblast Growth Factor Research
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Pancreatitis Pathology and Treatment
- Nuclear Receptors and Signaling
- Cancer-related gene regulation
University of Michigan
2018-2025
University of Pennsylvania
2021-2025
Cancer Research Institute
2022-2025
UPMC Hillman Cancer Center
2022-2024
California University of Pennsylvania
2023-2024
Michigan Medicine
2021-2022
Michigan Center for Translational Pathology
2020
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...
Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition 18 murine tissues 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals heterogeneity across tumors, identifies coordinated between immune cell subsets in pancreatic ductal adenocarcinoma. Expression CD105 demarks two stable...
Abstract Mutations in the KRAS oncogene are found more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), Gly-to-Asp mutations (KRASG12D) being most common. Here, we tested efficacy a small-molecule KRASG12D inhibitor, MRTX1133, implantable and autochthonous PDAC models an intact immune system. In vitro studies validated specificity potency MRTX1133. vivo, MRTX1133 prompted deep tumor regressions all tested, including complete or near-complete remissions after 14 days....
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity incompletely understood. The Hedgehog pathway functions in paracrine manner, with ligands secreted cancer cells signaling to stromal microenvironment. Previous reports investigating role have been contradictory, alternately...
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 Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by mutations 1,2 . RMC-7977 is highly selective inhibitor active GTP-bound forms KRAS, HRAS and NRAS, affinity for both mutant wild-type variants 3 More than 90% cases pancreatic ductal adenocarcinoma (PDAC) activating in KRAS 4 Here we assessed therapeutic comprehensive range PDAC models. We observed broad pronounced anti-tumour activity across models...
Pancreatic ductal adenocarcinoma (PDA) is accompanied by reprogramming of the local microenvironment, but changes at distal sites are poorly understood. We implanted biomaterial scaffolds, which act as an artificial premetastatic niche, into immunocompetent tumor-bearing and control mice, identified a unique tumor-specific gene expression signature that includes high C1qa , C1qb Trem2 Chil3 . Single-cell RNA sequencing mapped these genes to two distinct macrophage populations in one marked...
Mitochondrial glutamate-oxaloacetate transaminase 2 (GOT2) is part of the malate-aspartate shuttle, a mechanism by which cells transfer reducing equivalents from cytosol to mitochondria. GOT2 key component mutant KRAS (KRAS*)-mediated rewiring glutamine metabolism in pancreatic ductal adenocarcinoma (PDA). Here, we demonstrate that loss disturbs redox homeostasis and halts proliferation PDA vitro. knockdown (KD) cell lines vitro induced NADH accumulation, decreased Asp α-ketoglutarate (αKG)...
Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using mouse model of pancreatic ductal adenocarcinoma (PDAC) study tumor relapse following immunotherapy-induced responses, we find that is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), EMT-transcription factors ZEB1 and SNAIL functioning as master genetic epigenetic regulators this effect. in not due immunosuppression the immune microenvironment,...
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,...
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal cancer cells, as well intermediary individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach. Experimental Design: We performed subtyping on dataset containing 18 human PDAC samples identify multiple subtypes. generated patient-derived...
Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component tumor microenvironment, which includes immune, stromal, parenchymal cells. In particular, most PDACs characterized a hypovascular hypoxic environment that alters cell behavior limits efficacy chemotherapy immunotherapy. Characterization spatial features vascular niche could advance our understanding inter- intratumoral heterogeneity in PDAC. this study,...
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...
Pancreatic ductal adenocarcinoma (PDA) initiation and progression are accompanied by an immunosuppressive inflammatory response. Here, we evaluated the immunomodulatory role of chemosensory signaling in metaplastic tuft cells (MTCs) analyzing GNAT3, a gustatory pathway G-protein expressed MTCs, during PDA progression.
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) patients with tumors enriched for the basal-like molecular subtype exhibit enhanced resistance to standard-of-care treatments and have significantly worse overall survival compared classic subtype–enriched tumors. It is important develop genomic resources, enabling identification of novel putative targets in a statistically rigorous manner. Experimental Design: We compiled single-cell RNA sequencing (scRNA-seq) atlas human pancreas...
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