- Browse by Author
Browsing by Author "Dasari, Surendra"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers(American Society for Clinical Investigation, 2022-11-22) Hogenson, Tara L.; Xie, Hao; Phillips, William J.; Toruner, Merih D.; Li, Jenny J.; Horn, Isaac P.; Kennedy, Devin J.; Almada, Luciana L.; Marks, David L.; Carr, Ryan M.; Toruner, Murat; Sigafoos, Ashley N.; Koenig-Kappes, Amanda N.; Olson, Rachel Lo; Tolosa, Ezequiel J.; Zhang, Cheng; Li, Hu; Doles, Jason D.; Bleeker, Jonathan; Barrett, Michael T.; Boyum, James H.; Kipp, Benjamin R.; Mahipal, Amit; Hubbard, Joleen M.; Scheffler Hanson, Temperance J.; Petersen, Gloria M.; Dasari, Surendra; Oberg, Ann L.; Truty, Mark J.; Graham, Rondell P.; Levy, Michael J.; Zhu, Mojun; Billadeau, Daniel D.; Adjei, Alex A.; Dusetti, Nelson; Iovanna, Juan L.; Bekaii-Saab, Tanios S.; Ma, Wen Wee; Fernandez-Zapico, Martin E.; Anatomy, Cell Biology and Physiology, School of MedicineBACKGROUND: A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers. METHODS: We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments. RESULTS: We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures. CONCLUSION: While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers.Item Molecular signatures of inherited and acquired sporadic late onset nemaline myopathies(BMC, 2023-01-26) Nicolau, Stefan; Dasgupta, Aneesha; Dasari, Surendra; Charlesworth, M. Cristine; Johnson, Kenneth L.; Pandey, Akhilesh; Doles, Jason D.; Milone, Margherita; Anatomy, Cell Biology and Physiology, School of MedicineAcquired sporadic late onset nemaline myopathy (SLONM) and inherited nemaline myopathy (iNM) both feature accumulation of nemaline rods in muscle fibers. Unlike iNM, SLONM is amenable to therapy. The distinction between these disorders is therefore crucial when the diagnosis remains ambiguous after initial investigations. We sought to identify biomarkers facilitating this distinction and to investigate the pathophysiology of nemaline rod formation in these different disorders. Twenty-two muscle samples from patients affected by SLONM or iNM underwent quantitative histological analysis, laser capture microdissection for proteomic analysis of nemaline rod areas and rod-free areas, and transcriptomic analysis. In all iNM samples, nemaline rods were found in subsarcolemmal or central aggregates, whereas they were diffusely distributed within muscle fibers in most SLONM samples. In SLONM, muscle fibers harboring nemaline rods were smaller than those without rods. Necrotic fibers, increased endomysial connective tissue, and atrophic fibers filled with nemaline rods were more common in SLONM. Proteomic analysis detected differentially expressed proteins between nemaline rod areas and rod-free areas, as well as between SLONM and iNM. These differentially expressed proteins implicated immune, structural, metabolic, and cellular processes in disease pathophysiology. Notably, immunoglobulin overexpression with accumulation in nemaline rod areas was detected in SLONM. Transcriptomic analysis corroborated proteomic findings and further revealed substantial gene expression differences between SLONM and iNM. Overall, we identified unique pathological and molecular signatures associated with SLONM and iNM, suggesting distinct underlying pathophysiological mechanisms. These findings represent a step towards enhanced diagnostic tools and towards development of treatments for SLONM.