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478 results on '"Taraballi, Francesca"'

1. β-catenin mRNA encapsulated in SM-102 lipid nanoparticles enhances bone formation in a murine tibia fracture repair model.

Author

Nelson, Anna, Mancino, Chiara, Gao, Xueqin, Choe, Joshua, Chubb, Laura, Williams, Katherine, Czachor, Molly, Marcucio, Ralph, Taraballi, Francesca, Cooke, John, Huard, Johnny, Bahney, Chelsea, and Ehrhart, Nicole

Subjects
Canonical Wnt, Fracture healing, Gene therapy, Lipid nanoparticles, mRNA
Abstract

Fractures continue to be a global economic burden as there are currently no osteoanabolic drugs approved to accelerate fracture healing. In this study, we aimed to develop an osteoanabolic therapy which activates the Wnt/β-catenin pathway, a molecular driver of endochondral ossification. We hypothesize that using an mRNA-based therapeutic encoding β-catenin could promote cartilage to bone transformation formation by activating the canonical Wnt signaling pathway in chondrocytes. To optimize a delivery platform built on recent advancements in liposomal technologies, two FDA-approved ionizable phospholipids, DLin-MC3-DMA (MC3) and SM-102, were used to fabricate unique ionizable lipid nanoparticle (LNP) formulations and then tested for transfection efficacy both in vitro and in a murine tibia fracture model. Using firefly luciferase mRNA as a reporter gene to track and quantify transfection, SM-102 LNPs showed enhanced transfection efficacy in vitro and prolonged transfection, minimal fracture interference and no localized inflammatory response in vivo over MC3 LNPs. The generated β-cateninGOF mRNA encapsulated in SM-102 LNPs (SM-102-β-cateninGOF mRNA) showed bioactivity in vitro through upregulation of downstream canonical Wnt genes, axin2 and runx2. When testing SM-102-β-cateninGOF mRNA therapeutic in a murine tibia fracture model, histomorphometric analysis showed increased bone and decreased cartilage composition with the 45 μg concentration at 2 weeks post-fracture. μCT testing confirmed that SM-102-β-cateninGOF mRNA promoted bone formation in vivo, revealing significantly more bone volume over total volume in the 45 μg group. Thus, we generated a novel mRNA-based therapeutic encoding a β-catenin mRNA and optimized an SM-102-based LNP to maximize transfection efficacy with a localized delivery.

Published
2024

10. Heterologous mRNA-protein vaccination with Tc24 induces a robust cellular immune response against Trypanosoma cruzi, characterized by an increased level of polyfunctional CD8+ T-cells

Author

Poveda, Cristina, Leão, Ana Carolina, Mancino, Chiara, Taraballi, Francesca, Chen, Yi-Lin, Adhikari, Rakesh, Villar, Maria Jose, Kundu, Rakhi, Nguyen, Duc M., Versteeg, Leroy, Strych, Ulrich, Hotez, Peter J., Bottazzi, Maria Elena, Pollet, Jeroen, and Jones, Kathryn M.

Published
2023
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13. Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Elbow and Upper Extremity: An Orthoregeneration Network Foundation Review.

Author

Lazzaretti Fernandes, Tiago, Taraballi, Francesca, Shao, Zhenxing, Roessler, Philip P., and Cardona-Ramírez, Sebastián

Abstract

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the elbow and upper extremity, including the tendons (lateral epicondylitis, medial epicondylitis, biceps tendonitis, triceps tendonitis), articular cartilage (osteoarthritis, osteochondral lesions), and bone (fractures, nonunions, avascular necrosis, osteonecrosis). Promising and established treatment modalities include hyaluronic acid; botulinum toxin; corticosteroids; leukocyte-rich and leukocyte-poor platelet-rich plasma; autologous blood; bone marrow aspirate comprising mesenchymal stromal cells (alternatively termed medicinal signaling cells and frequently mesenchymal stem cells [MSCs]) and bone marrow aspirate concentrate; MSCs harvested from adipose and skin (dermis) sources; vascularized bone grafts; bone morphogenic protein scaffold made from osteoinductive and conductive β-tricalcium phosphate and poly-ε-caprolactone with hydrogels, human MSCs, and matrix metalloproteinases; and collagen sponge. Autologous blood preparations such as autologous blood injections and platelet-rich plasma show positive outcomes for nonresponsive tendinopathy. In addition, cellular therapies such as tissue-derived tenocyte-like cells and MSCs show a promising ability to regulate degenerative processes by modulating tissue response to inflammation and preventing continuous degradation and support tissue restoration. Level V, expert opinion. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Harnessing RNA Technology to Advance Therapeutic Vaccine Antigens against Chagas Disease

Author

Mancino, Chiara, Pollet, Jeroen, Zinger, Assaf, Jones, Kathryn M., Villar, Maria José, Leao, Ana Carolina, Adhikari, Rakesh, Versteeg, Leroy, Tyagi Kundu, Rakhi, Strych, Ulrich, Giordano, Federica, Hotez, Peter J., Bottazzi, Maria Elena, Taraballi, Francesca, Poveda, Cristina, Mancino, Chiara, Pollet, Jeroen, Zinger, Assaf, Jones, Kathryn M., Villar, Maria José, Leao, Ana Carolina, Adhikari, Rakesh, Versteeg, Leroy, Tyagi Kundu, Rakhi, Strych, Ulrich, Giordano, Federica, Hotez, Peter J., Bottazzi, Maria Elena, Taraballi, Francesca, and Poveda, Cristina

Published
2024

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Author

Nelson, Anna, Nelson, Anna, Mancino, Chiara, Gao, Xueqin, Choe, Joshua, Chubb, Laura, Williams, Katherine, Czachor, Molly, Marcucio, Ralph, Taraballi, Francesca, Cooke, John, Huard, Johnny, Bahney, Chelsea, Ehrhart, Nicole, Nelson, Anna, Nelson, Anna, Mancino, Chiara, Gao, Xueqin, Choe, Joshua, Chubb, Laura, Williams, Katherine, Czachor, Molly, Marcucio, Ralph, Taraballi, Francesca, Cooke, John, Huard, Johnny, Bahney, Chelsea, and Ehrhart, Nicole

Published
2024

30. Metal–Organic Framework as a New Type of Magnetothermally‐Triggered On‐Demand Release Carrier

Author

Ge, Xueying, primary, Mohapatra, Jeotikanta, additional, Silva, Enya, additional, He, Guihua, additional, Gong, Lingshan, additional, Lyu, Tengteng, additional, Madhogaria, Richa P., additional, Zhao, Xin, additional, Cheng, Yuchuan, additional, Al‐Enizi, Abdullah M., additional, Nafady, Ayman, additional, Tian, Jian, additional, Liu, J. Ping, additional, Phan, Manh‐Huong, additional, Taraballi, Francesca, additional, Pettigrew, Roderic I., additional, and Ma, Shengqian, additional

Published
2023
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31. Intramuscular but not nebulized administration of a mRNA vaccine against Rhodococcus equi stimulated humoral immune responses in neonatal foals

Author

Legere, Rebecca M., primary, Poveda, Cristina, additional, Ott, Jeannine A., additional, Bray, Jocelyne M., additional, Villafone, Emma G., additional, Silveira, Bibiana Petri da, additional, Kahn, Susanne K., additional, Martin, Cameron L., additional, Mancino, Chiara, additional, Taraballi, Francesca, additional, Criscitiello, Michael F., additional, Berghman, Luc, additional, Bordin, Angela I., additional, Pollet, Jeroen, additional, and Cohen, Noah D., additional

Published
2023
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39. Systemic Cisplatin Does Not Affect the Bone Regeneration Process in a Critical Size Defect Murine Model

Author

Brozovich, Ava A., Lenna, Stefania, Brenner, Carson, Serpelloni, Stefano, Paradiso, Francesca, McCulloch, Patrick, Yustein, Jason T., Weiner, Bradley, and Taraballi, Francesca

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor, and the current standard of care for OS includes neoadjuvant chemotherapy, followed by an R0 surgical resection of the primary tumor, and then postsurgical adjuvant chemotherapy. Bone reconstruction following OS resection is particularly challenging due to the size of the bone voids and because patients are treated with adjuvant and neoadjuvant systemic chemotherapy, which theoretically could impact bone formation. We hypothesized that an osteogenic material could be used in order to induce bone regeneration when adjuvant or neoadjuvant chemotherapy is given. We utilized a biomimetic, biodegradable magnesium-doped hydroxyapatite/type I collagen composite material (MHA/Coll) to promote bone regeneration in the presence of systemic chemotherapy in a murine critical size defect model. We found that in the presence of neoadjuvant or adjuvant chemotherapy, MHA/Coll is able to enhance and increase bone formation in a murine critical size defect model (11.16 ± 2.55 or 13.80 ± 3.18 versus 8.70 ± 0.81 mm3) for pre-op cisplatin + MHA/Coll (p-value = 0.1639) and MHA/Coll + post-op cisplatin (p-value = 0.1538), respectively, at 12 weeks. These findings indicate that neoadjuvant and adjuvant chemotherapy will not affect the ability of a biomimetic scaffold to regenerate bone to repair bone voids in OS patients. This preliminary data demonstrates that bone regeneration can occur in the presence of chemotherapy, suggesting that there may not be a necessity to modify the current standard of care concerning neoadjuvant and adjuvant chemotherapy for the treatment of metastatic sites or micrometastases.

Published
2024
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41. Mice deficient for G-protein coupled receptor 75 display altered presynaptic structural protein expression and disrupted fear conditioning recall

Author

Speidell, A, Walton, S, Campbell, L, Tomassoni-Ardori, F, Tessarollo, L, Corbo, C, Taraballi, F, Mocchetti, I, Speidell, Andrew, Walton, Sofia, Campbell, Lee A, Tomassoni-Ardori, Francesco, Tessarollo, Lino, Corbo, Claudia, Taraballi, Francesca, Mocchetti, Italo, Speidell, A, Walton, S, Campbell, L, Tomassoni-Ardori, F, Tessarollo, L, Corbo, C, Taraballi, F, Mocchetti, I, Speidell, Andrew, Walton, Sofia, Campbell, Lee A, Tomassoni-Ardori, Francesco, Tessarollo, Lino, Corbo, Claudia, Taraballi, Francesca, and Mocchetti, Italo

Abstract

There are a number of G-protein-coupled receptors (GPCRs) that are considered “orphan receptors” because the information on their known ligands is incomplete. Yet, these receptors are important targets to characterize, as the discovery of their ligands may lead to potential new therapies. GPR75 was recently deorphanized because at least two ligands appear to bind to it, the chemokine CCL5 and the eicosanoid 20-Hydroxyeicosatetraenoic acid. Recent reports suggest that GPR75 may play a role in regulating insulin secretion and obesity. However, little is known about the function of this receptor in the brain. To study the function of GPR75, we have generated a knockout (KO) mouse model of this receptor and we evaluated the role that this receptor plays in the adult hippocampus by an array of histological, proteomic, and behavioral endpoints. Using RNAscope® technology, we identified GPR75 puncta in several Rbfox3-/NeuN-positive cells in the hippocampus, suggesting that this receptor has a neuronal expression. Proteomic analysis of the hippocampus in 3-month-old GPR75 KO animals revealed that several markers of synapses, including synapsin I and II are downregulated compared with wild type (WT). To examine the functional consequence of this down-regulation, WT and GPR75 KO mice were tested on a hippocampal-dependent behavioral task. Both contextual memory and anxiety-like behaviors were significantly altered in GPR75 KO, suggesting that GPR75 plays a role in hippocampal activity.

Published
2023

43. Supplementary Figures S1-S5 from Microparticle-Delivered Cxcl9 Prolongs Braf Inhibitor Efficacy in Melanoma

Author

Romano, Gabriele, primary, Paradiso, Francesca, primary, Li, Peng, primary, Shukla, Pooja, primary, Barger, Lindsay N., primary, El Naggar, Olivia, primary, Miller, John P., primary, Liang, Roger J., primary, Helms, Timothy L., primary, Lazar, Alexander J., primary, Wargo, Jennifer A., primary, Taraballi, Francesca, primary, Costello, James C., primary, and Kwong, Lawrence N., primary

Published
2023
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44. Data from Microparticle-Delivered Cxcl9 Prolongs Braf Inhibitor Efficacy in Melanoma

Author

Romano, Gabriele, primary, Paradiso, Francesca, primary, Li, Peng, primary, Shukla, Pooja, primary, Barger, Lindsay N., primary, El Naggar, Olivia, primary, Miller, John P., primary, Liang, Roger J., primary, Helms, Timothy L., primary, Lazar, Alexander J., primary, Wargo, Jennifer A., primary, Taraballi, Francesca, primary, Costello, James C., primary, and Kwong, Lawrence N., primary

Published
2023
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45. Supplementary Tables from Microparticle-Delivered Cxcl9 Prolongs Braf Inhibitor Efficacy in Melanoma

Author

Romano, Gabriele, primary, Paradiso, Francesca, primary, Li, Peng, primary, Shukla, Pooja, primary, Barger, Lindsay N., primary, El Naggar, Olivia, primary, Miller, John P., primary, Liang, Roger J., primary, Helms, Timothy L., primary, Lazar, Alexander J., primary, Wargo, Jennifer A., primary, Taraballi, Francesca, primary, Costello, James C., primary, and Kwong, Lawrence N., primary

Published
2023
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