Browsing by Author "Eisenbarth, David"

Now showing 1 - 3 of 3
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    Glioblastoma heterogeneity at single cell resolution
    (Springer Nature, 2023) Eisenbarth, David; Wang, Y. Alan; Medicine, School of Medicine
    Glioblastoma (GBM) is one of the deadliest types of cancer and highly refractory to chemoradiation and immunotherapy. One of the main reasons for this resistance to therapy lies within the heterogeneity of the tumor and its associated microenvironment. The vast diversity of cell states, composition of cells, and phenotypical characteristics makes it difficult to accurately classify GBM into distinct subtypes and find effective therapies. The advancement of sequencing technologies in recent years has further corroborated the heterogeneity of GBM at the single cell level. Recent studies have only begun to elucidate the different cell states present in GBM and how they correlate with sensitivity to therapy. Furthermore, it has become clear that GBM heterogeneity not only depends on intrinsic factors but also strongly differs between new and recurrent GBM, and treatment naïve and experienced patients. Understanding and connecting the complex cellular network that underlies GBM heterogeneity will be indispensable in finding new ways to tackle this deadly disease. Here, we present an overview of the multiple layers of GBM heterogeneity and discuss novel findings in the age of single cell technologies.
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    PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
    (Elsevier, 2024) Ku, Bomin; Eisenbarth, David; Baek, Seonguk; Jeong, Tae-Keun; Kang, Ju-Gyeong; Hwang, Daehee; Noh, Myung-Giun; Choi, Chan; Choi, Sungwoo; Seol, Taejun; Kim, Yun-Hee; Woo, Sang Myung; Kong, Sun-Young; Lim, Dae-Sik; Medicine, School of Medicine
    Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal types of cancer, and novel treatment regimens are direly needed. Epigenetic regulation contributes to the development of various cancer types, but its role in the development of and potential as a therapeutic target for PDAC remains underexplored. Here, we show that PRMT1 is highly expressed in murine and human pancreatic cancer and is essential for cancer cell proliferation and tumorigenesis. Deletion of PRMT1 delays pancreatic cancer development in a KRAS-dependent mouse model, and multi-omics analyses reveal that PRMT1 depletion leads to global changes in chromatin accessibility and transcription, resulting in reduced glycolysis and a decrease in tumorigenic capacity. Pharmacological inhibition of PRMT1 in combination with gemcitabine has a synergistic effect on pancreatic tumor growth in vitro and in vivo. Collectively, our findings implicate PRMT1 as a key regulator of pancreatic cancer development and a promising target for combination therapy.
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    Protocol to calculate the synergy of drug combinations in organoids and primary cells from murine tumors
    (Elsevier, 2024-10-01) Eisenbarth, David; Ku, Bomin; Lim, Dae-Sik; Medicine, School of Medicine
    Evaluating the synergy of drug combinations is crucial in advancing treatment regimens. Here, we present a protocol to establish primary cells and organoids from murine tumors and calculate drug synergy. We describe all necessary cell culture procedures, including establishing primary cultures, setting up treatment groups, and detecting cell viability. We then outline how to calculate the synergy score based on a bioinformatical pipeline. This approach applies to any disease model in which a combination of drugs needs to be evaluated. For complete details on the use and execution of this protocol, please refer to Ku et al.1.