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17 results on '"Schweickert, Patrick G."'

4. Supplementary Data from Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1–Dependent Immune Evasion

Author

Yang, Yi, primary, Stang, Amanda, primary, Schweickert, Patrick G., primary, Lanman, Nadia A., primary, Paul, Erin N., primary, Monia, Brett P., primary, Revenko, Alexey S., primary, Palumbo, Joseph S., primary, Mullins, Eric S., primary, Elzey, Bennett D., primary, Janssen, Edith M., primary, Konieczny, Stephen F., primary, and Flick, Matthew J., primary

Published
2023
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5. Data from Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1–Dependent Immune Evasion

Author

Yang, Yi, primary, Stang, Amanda, primary, Schweickert, Patrick G., primary, Lanman, Nadia A., primary, Paul, Erin N., primary, Monia, Brett P., primary, Revenko, Alexey S., primary, Palumbo, Joseph S., primary, Mullins, Eric S., primary, Elzey, Bennett D., primary, Janssen, Edith M., primary, Konieczny, Stephen F., primary, and Flick, Matthew J., primary

Published
2023
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7. Anti-TIGIT antibodies promote immune activation relevant to targeting stem-like and tumor-specific T cells in combination with anti-PD-1

Author

Sivick Gauthier, Kelsey E, primary, Piovesan, Dana, additional, de Groot, Amber E, additional, Reiner, Gabrielle L, additional, Schweickert, Patrick G, additional, Soriano, Ferdie, additional, Chen, Ada, additional, Singh, Hema, additional, Zhao, Xiaoning, additional, Seitz, Lisa, additional, Reddy, Anita, additional, Young, Stephen W, additional, Walker, Nigel, additional, and Walters, Matthew J, additional

Published
2022
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8. Abstract P206: AB521 potently and selectively inhibits pro-tumorigenic gene transcription by Hypoxia-Inducible Factor (HIF)-2α in vitro and in vivo

Author

Gauthier, Kelsey E. Sivick, primary, Piovesan, Dana, additional, Cho, Soonweng, additional, Lawson, Kenneth V., additional, Schweickert, Patrick G., additional, Lopez, Alejandra, additional, Liu, Suan, additional, Park, Timothy, additional, Mailyan, Artur, additional, Fournier, Jeremy T. A., additional, Beatty, Joel W., additional, Drew, Samuel L., additional, Kalisiak, Jarek, additional, Gal, Balint, additional, Mata, Guillaume, additional, Wang, Zhang, additional, Rosen, Brandon R., additional, Hardman, Clayton, additional, Epplin, Matthaw P., additional, Yu, Kai, additional, Haelsig, Karl T., additional, Jin, Lixia, additional, Ginn, Elaine, additional, Au, Jennie, additional, Meleza, Cesar A., additional, Tencer, Joel, additional, Pham, Amber, additional, Kwon, Hyock J., additional, Young, Stephen W., additional, Leleti, Manmohan, additional, Powers, Jay P., additional, and Walters, Matthew J., additional

Published
2021
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10. Investigating the respective roles of SOX9 and PAR1 in pancreatic ductal adenocarcinoma initiation and immune evasion

Author

Schweickert, Patrick G

Subjects
endocrine system diseases, 60405 Gene Expression (incl. Microarray and other genome-wide approaches), FOS: Biological sciences, FOS: Clinical medicine, Immunology, Cell Biology, Cancer
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a poorly immune responsive, treatment refractory disease, representing the fourth leading cause of cancer deaths in the United States. A lack of significant improvements in patient prognoses over the last few decades highlights the necessity for a more basic understanding of how PDAC develops and progresses. To this end, the research outlined here investigates the contributions of SOX9 and PAR1 in PDAC initiation and tumor immune evasion, respectively. SOX9 is a developmental transcription factor important for proper pancreas development that is restricted to only a small subset of cells in the adult organ. However, SOX9 is aberrantly expressed in precancerous lesions of the pancreas and throughout PDAC development. Using genetically engineered mouse models we demonstrated that PDAC precursor lesions cannot form in the absence of SOX9 and conversely formed at an accelerated rate when SOX9 was ectopically expressed. Surprisingly deletion of SOX9 in primary mouse PDAC cell lines had no impact on tumor growth in subcutaneous allograft experiments, indicating that although SOX9 expression is necessary for PDAC initiation, it is dispensable in many cases for tumor maintenance and growth. Research investigating the transcriptional changes induced by SOX9 prior to lesion formation is ongoing to identify additional downstream factors critical for disease initiation. Previous research has shown that PDAC tumors frequently display low levels of immune infiltration, which is a major limitation for the use of immune-based therapeutics and is generally an unfavorable prognostic factor. We show that in primary mouse tumor cells ablation of the thrombin receptor PAR1 caused a significant increase in the infiltration of tumor targeting CD8a+ T cells which in turn were found to eliminate PAR1 knockout tumors. When PAR1KO and PAR1 expressing PDAC tumor cells were co-injected into wild type mice, cells lacking PAR1 were preferentially targeted and eliminated by the immune system, indicating that PAR1 provides cell autonomous protection during an active anti-tumor adaptive immune response. Furthermore, we identified a previously underappreciated association between PAR1-mediated expression of Csf2 and Ptgs2, and PDAC tumor immune evasion. Together these findings provide novel insights into the mechanisms and drivers of PDAC initiation and immune evasion.

Published
2020
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12. Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1–Dependent Immune Evasion

Author

Yang, Yi, primary, Stang, Amanda, additional, Schweickert, Patrick G., additional, Lanman, Nadia A., additional, Paul, Erin N., additional, Monia, Brett P., additional, Revenko, Alexey S., additional, Palumbo, Joseph S., additional, Mullins, Eric S., additional, Elzey, Bennett D., additional, Janssen, Edith M., additional, Konieczny, Stephen F., additional, and Flick, Matthew J., additional

Published
2019
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14. Induced PTF 1a expression in pancreatic ductal adenocarcinoma cells activates acinar gene networks, reduces tumorigenic properties, and sensitizes cells to gemcitabine treatment

Author

Jakubison, Brad L., primary, Schweickert, Patrick G., additional, Moser, Sarah E., additional, Yang, Yi, additional, Gao, Hongyu, additional, Scully, Kathleen, additional, Itkin‐Ansari, Pamela, additional, Liu, Yunlong, additional, and Konieczny, Stephen F., additional

Published
2018
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15. Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar–ductal metaplasia

Author

Liu, Xin, primary, Pitarresi, Jason R., additional, Cuitiño, Maria C., additional, Kladney, Raleigh D., additional, Woelke, Sarah A., additional, Sizemore, Gina M., additional, Nayak, Sunayana G., additional, Egriboz, Onur, additional, Schweickert, Patrick G., additional, Yu, Lianbo, additional, Trela, Stefan, additional, Schilling, Daniel J., additional, Halloran, Shannon K., additional, Li, Maokun, additional, Dutta, Shourik, additional, Fernandez, Soledad A., additional, Rosol, Thomas J., additional, Lesinski, Gregory B., additional, Shakya, Reena, additional, Ludwig, Thomas, additional, Konieczny, Stephen F., additional, Leone, Gustavo, additional, Wu, Jinghai, additional, and Ostrowski, Michael C., additional

Published
2016
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17. Induced PTF1a expression in pancreatic ductal adenocarcinoma cells activates acinar gene networks, reduces tumorigenic properties, and sensitizes cells to gemcitabine treatment.

Author

Jakubison, Brad L., Schweickert, Patrick G., Moser, Sarah E., Yang, Yi, Gao, Hongyu, Scully, Kathleen, Itkin‐Ansari, Pamela, Liu, Yunlong, and Konieczny, Stephen F.

Abstract

Pancreatic acinar cells synthesize, package, and secrete digestive enzymes into the duodenum to aid in nutrient absorption and meet metabolic demands. When exposed to cellular stresses and insults, acinar cells undergo a dedifferentiation process termed acinar–ductal metaplasia (ADM). ADM lesions with oncogenic mutations eventually give rise to pancreatic ductal adenocarcinoma (PDAC). In healthy pancreata, the basic helix‐loop‐helix (bHLH) factors MIST1 and PTF1a coordinate an acinar‐specific transcription network that maintains the highly developed differentiation status of the cells, protecting the pancreas from undergoing a transformative process. However, when MIST1 and PTF1a gene expression is silenced, cells are more prone to progress to PDAC. In this study, we tested whether induced MIST1 or PTF1a expression in PDAC cells could (i) re‐establish the transcriptional program of differentiated acinar cells and (ii) simultaneously reduce tumor cell properties. As predicted, PTF1a induced gene expression of digestive enzymes and acinar‐specific transcription factors, while MIST1 induced gene expression of vesicle trafficking molecules as well as activation of unfolded protein response components, all of which are essential to handle the high protein production load that is characteristic of acinar cells. Importantly, induction of PTF1a in PDAC also influenced cancer‐associated properties, leading to a decrease in cell proliferation, cancer stem cell numbers, and repression of key ATP‐binding cassette efflux transporters resulting in heightened sensitivity to gemcitabine. Thus, activation of pancreatic bHLH transcription factors rescues the acinar gene program and decreases tumorigenic properties in pancreatic cancer cells, offering unique opportunities to develop novel therapeutic intervention strategies for this deadly disease. [ABSTRACT FROM AUTHOR]

Published
2018
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