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Targeting epigenetic regulators using bacterial macromolecule delivery

Description: PUBLIC HEALTH RELEVANCE: The experimental plan describes a therapeutic strategy to target epigenetic tumor regulators by using bacteria to controllably deliver genes and proteins into cancer cells. In this project, bacteria will be engineered to deliver shRNA, targeting NIPP1 and EZH2, and NIPP1-based peptides that dissociate NIPP1:PP1 complexes. This research will establish a new therapeutic platform that will enable targeting of cancer genes for which no therapy currently exists.
Funding type: research
Funder scheme: R01
Start date: 2014-09-01
End date: 2020-08-31
Investigator: NEIL S. FORBES
Institution: UNIVERSITY OF MASSACHUSETTS AMHERST
Subfield: Biotechnology
Funded outputs count: 25
Funder award ID: R01CA188382
OpenAlex ID: G2881906363
Salmonella vector creates de novo parvovirus that reduces solid tumors and forms antitumor immune memory
2026 · Shradha Khanduja, Vishnu Raman, et al. · Cell Reports Medicine · 1
Controlling intracellular protein delivery, tumor colonization and tissue distribution using flhDC in clinically relevant ΔsseJ Salmonella
2024 · Vishnu Raman, Christopher L. Hall, et al. · Molecular Therapy · 7
Setting “cold” tumors on fire: Cancer therapy with live tumor-targeting bacteria
2024 · Simin Manole, Dinh-Huy Nguyen, et al. · Med · 17
Controlled production of lipopolysaccharides increases immune activation in Salmonella treatments of cancer
2024 · Lars M. Howell, Simin Manole, et al. · Microbial Biotechnology · 8
Intracellular delivery of oncolytic viruses with engineered Salmonella causes viral replication and cell death
2024 · Shradha Khanduja, Shoshana M.K. Bloom, et al. · iScience · 17
Intracellular Salmonella delivery of an exogenous immunization antigen refocuses CD8 T cells against cancer cells, eliminates pancreatic tumors and forms antitumor immunity
2023 · Vishnu Raman, Lars M. Howell, et al. · Frontiers in Immunology · 24
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Build-a-bug workshop: Using microbial-host interactions and synthetic biology tools to create cancer therapies
2023 · Vishnu Raman, Chinmay P. Deshpande, et al. · Cell Host & Microbe · 37
Bacterial delivery of therapeutic proteins to the nuclei of cancer cells
2023 · Shoshana M. K. Bloom, Nicholas O'Hare, et al. · Biotechnology and Bioengineering · 3
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Microbial Imbalance Induces Inflammation by Promoting Salmonella Penetration through the Mucosal Barrier
2022 · Abhinav Sharma, Vishnu Raman, et al. · ACS Infectious Diseases · 8
Intracellular delivery of protein drugs with an autonomously lysing bacterial system reduces tumor growth and metastases
2021 · Vishnu Raman, Nele Van Dessel, et al. · Nature Communications · 177
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Bacteria-based immune therapies for cancer treatment
2021 · Lars M. Howell, Neil S. Forbes · Seminars in Cancer Biology · 47
Mucus blocks probiotics but increases penetration of motile pathogens and induces TNF‐α and IL‐8 secretion
2020 · Abhinav Sharma, Vishnu Raman, et al. · Biotechnology and Bioengineering · 9
In Vitro Reconstitution of an Intestinal Mucus Layer Shows That Cations and pH Control the Pore Structure That Regulates Its Permeability and Barrier Function
2020 · Abhinav Sharma, Jun-Goo Kwak, et al. · ACS Applied Bio Materials · 42
Phosphatase Regulator NIPP1 Restrains Chemokine-Driven Skin Inflammation
2020 · Iris Verbinnen, Marloes Jonkhout, et al. · Journal of Investigative Dermatology · 7
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Detection of tumors with fluoromarker‐releasing bacteria
2019 · Jan T. Panteli, Nele Van Dessel, et al. · International Journal of Cancer · 20
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The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella
2019 · Vishnu Raman, Nele Van Dessel, et al. · Journal for ImmunoTherapy of Cancer · 34
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White paper on microbial anti-cancer therapy and prevention
2018 · Neil S. Forbes, Robert S. Coffin, et al. · Journal for ImmunoTherapy of Cancer · 174
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Tissue transport affects how treatment scheduling increases the efficacy of chemotherapeutic drugs
2017 · Dan E. Ganz, Briana Sexton-Stallone, et al. · Journal of Theoretical Biology · 2
Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cell masses
2016 · Jan T. Panteli, Neil S. Forbes · Biotechnology and Bioengineering · 36
Microfluidic Device to Quantify the Behavior of Therapeutic Bacteria in Three-Dimensional Tumor Tissue
2016 · Emily L. Brackett, Charles A. Swofford, et al. · Methods in molecular biology · 5
Persistent enhancement of bacterial motility increases tumor penetration
2015 · Dana N. Thornlow, Emily L. Brackett, et al. · Biotechnology and Bioengineering · 39
Potent and Tumor specific: Arming Bacteria With Therapeutic Proteins
2015 · Nele Van Dessel, Charles A Swofford, et al. · Therapeutic Delivery · 52
Genetically modified bacteria as a tool to detect microscopic solid tumor masses with triggered release of a recombinant biomarker
2015 · Jan T. Panteli, Brittany A. Forkus, et al. · Integrative Biology · 46
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Quorum-sensing Salmonella selectively trigger protein expression within tumors
2015 · Charles A. Swofford, Nele Van Dessel, et al. · Proceedings of the National Academy of Sciences · 147
Trg-deficient Salmonella colonize quiescent tumor regions by exclusively penetrating or proliferating
2014 · Miaomin Zhang, Neil S. Forbes · Journal of Controlled Release · 46
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