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212 results on '"Danino, Tal"'

1. Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia

Author

Gurbatri, Candice R., Radford, Georgette A., Vrbanac, Laura, Im, Jongwon, Thomas, Elaine M., Coker, Courtney, Taylor, Samuel R., Jang, YoungUk, Sivan, Ayelet, Rhee, Kyu, Saleh, Anas A., Chien, Tiffany, Zandkarimi, Fereshteh, Lia, Ioana, Lannagan, Tamsin R. M., Wang, Tongtong, Wright, Josephine A., Kobayashi, Hiroki, Ng, Jia Q., Lawrence, Matt, Sammour, Tarik, Thomas, Michelle, Lewis, Mark, Papanicolas, Lito, Perry, Joanne, Fitzsimmons, Tracy, Kaazan, Patricia, Lim, Amanda, Stavropoulos, Alexandra M., Gouskos, Dion A., Marker, Julie, Ostroff, Cheri, Rogers, Geraint, Arpaia, Nicholas, Worthley, Daniel L., Woods, Susan L., and Danino, Tal

Published
2024
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5. Syndemic: Using Game-Based Learning to Engage Students in the Human Microbiome

Author

Ruskin, Emma, Danino, Tal, Tippins, Deborah J., Series Editor, Pontius, Joel, Series Editor, Cooper, Caren, Editorial Board Member, Espinet, Mariona, Editorial Board Member, Greenwood, David, Editorial Board Member, McKinley, Elizabeth, Editorial Board Member, Pierce, Clayton, Editorial Board Member, Rivera Maulucci, Maria S, Editorial Board Member, Reis, Giuliano, Editorial Board Member, Stewart, Arthur J., Editorial Board Member, Rivera Maulucci, María S., editor, Pfirman, Stephanie, editor, and Callahan, Hilary S., editor

Published
2023
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6. Segmentation with Residual Attention U-Net and an Edge-Enhancement Approach Preserves Cell Shape Features

Author

Zhu, Nanyan, Liu, Chen, Singer, Zakary S., Danino, Tal, Laine, Andrew F., and Guo, Jia

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Computer Vision and Pattern Recognition, Electrical Engineering and Systems Science - Image and Video Processing, I.4.6, I.4.7, I.5.1, I.5.2
Abstract

The ability to extrapolate gene expression dynamics in living single cells requires robust cell segmentation, and one of the challenges is the amorphous or irregularly shaped cell boundaries. To address this issue, we modified the U-Net architecture to segment cells in fluorescence widefield microscopy images and quantitatively evaluated its performance. We also proposed a novel loss function approach that emphasizes the segmentation accuracy on cell boundaries and encourages shape feature preservation. With a 97% sensitivity, 93% specificity, 91% Jaccard similarity, and 95% Dice coefficient, our proposed method called Residual Attention U-Net with edge-enhancement surpassed the state-of-the-art U-Net in segmentation performance as evaluated by the traditional metrics. More remarkably, the same proposed candidate also performed the best in terms of the preservation of valuable shape features, namely area, eccentricity, major axis length, solidity and orientation. These improvements on shape feature preservation can serve as useful assets for downstream cell tracking and quantification of changes in cell statistics or features over time., Comment: 7 pages, 4 figures, 1 table. Nanyan Zhu and Chen Liu share equal contribution and are listed as co-first authors

Published
2020

10. The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis

Author

Kobayashi, Hiroki, Gieniec, Krystyna A., Lannagan, Tamsin R.M., Wang, Tongtong, Asai, Naoya, Mizutani, Yasuyuki, Iida, Tadashi, Ando, Ryota, Thomas, Elaine M., Sakai, Akihiro, Suzuki, Nobumi, Ichinose, Mari, Wright, Josephine A., Vrbanac, Laura, Ng, Jia Q., Goyne, Jarrad, Radford, Georgette, Lawrence, Matthew J., Sammour, Tarik, Hayakawa, Yoku, Klebe, Sonja, Shin, Alice E., Asfaha, Samuel, Bettington, Mark L., Rieder, Florian, Arpaia, Nicholas, Danino, Tal, Butler, Lisa M., Burt, Alastair D., Leedham, Simon J., Rustgi, Anil K., Mukherjee, Siddhartha, Takahashi, Masahide, Wang, Timothy C., Enomoto, Atsushi, Woods, Susan L., and Worthley, Daniel L.

Published
2022
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14. Abstract B015: Toxin-producing bacterial therapy limits tumor growth in autochthonous mouse models of pancreatic ductal adenocarcinoma

Author

Decker-Farrell, Amanda R., primary, Sastra, Stephen A., additional, Harimoto, Tetsuhiro, additional, Hasselluhn, Marie C., additional, Li, Fangda, additional, Vincent, Rosa, additional, Palermo, Carmine F., additional, Ballister, Edward R., additional, Danino, Tal, additional, and Olive, Kenneth P., additional

Published
2024
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20. Probiotic-guided CAR-T cells for solid tumor targeting

Author

Vincent, Rosa L., primary, Gurbatri, Candice R., additional, Li, Fangda, additional, Vardoshvili, Ana, additional, Coker, Courtney, additional, Im, Jongwon, additional, Ballister, Edward R., additional, Rouanne, Mathieu, additional, Savage, Thomas, additional, de los Santos-Alexis, Kenia, additional, Redenti, Andrew, additional, Brockmann, Leonie, additional, Komaranchath, Meghna, additional, Arpaia, Nicholas, additional, and Danino, Tal, additional

Published
2023
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22. Probiotic neoantigen delivery vectors for precision cancer immunotherapy

Author

Redenti, Andrew, primary, Im, Jongwon, additional, Redenti, Benjamin, additional, Li, Fangda, additional, Rouanne, Mathieu, additional, Sheng, Zeren, additional, Sun, William, additional, Gurbatri, Candice R., additional, Huang, Shunyu, additional, Komaranchath, Meghna, additional, Jang, YoungUk, additional, Hahn, Jaeseung, additional, Ballister, Edward R., additional, Vincent, Rosa L., additional, Vardoshivilli, Ana, additional, Danino, Tal, additional, and Arpaia, Nicholas, additional

Published
2023
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26. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine

Author

Geller, Leore T., Barzily-Rokni, Michal, Danino, Tal, Jonas, Oliver H., Shental, Noam, Nejman, Deborah, Gavert, Nancy, Zwang, Yaara, Cooper, Zachary A., Shee, Kevin, Thaiss, Christoph A., Reuben, Alexandre, Livny, Jonathan, Avraham, Roi, Frederick, Dennie T., Ligorio, Matteo, Chatman, Kelly, Johnston, Stephen E., Mosher, Carrie M., Brandis, Alexander, Fuks, Garold, Gurbatri, Candice, Gopalakrishnan, Vancheswaran, Kim, Michael, Hurd, Mark W., Katz, Matthew, Fleming, Jason, Maitra, Anirban, Smith, David A., Skalak, Matt, Bu, Jeffrey, Michaud, Monia, Trauger, Sunia A., Barshack, Iris, Golan, Talia, Sandbank, Judith, Flaherty, Keith T., Mandinova, Anna, Garrett, Wendy S., Thayer, Sarah P., Ferrone, Cristina R., Huttenhower, Curtis, Bhatia, Sangeeta N., Gevers, Dirk, Wargo, Jennifer A., Golub, Todd R., and Straussman, Ravid

Published
2017

29. Colorectal cancer detection and treatment with engineered probiotics

Author

Gurbatri, Candice R, primary, Radford, Georgette, additional, Vrbanac, Laura, additional, Coker, Courtney, additional, Im, Jongwon, additional, Taylor, Samuel R, additional, Jang, YoungUk, additional, Sivan, Ayelet, additional, Rhee, Kyu, additional, Saleh, Anas A, additional, Chien, Tiffany, additional, Zandkarimi, Fereshteh, additional, Lia, Ioana, additional, Lannagan, Tamsin RM, additional, Wang, Tongtong, additional, Wright, Josephine A, additional, Thomas, Elaine, additional, Kobayashi, Hiroki, additional, Ng, Jia Q, additional, Lawrence, Matt, additional, Sammour, Tarik, additional, Thomas, Michelle, additional, Lewis, Mark, additional, Papanicolas, Lito, additional, Perry, Joanne, additional, Fitzsimmons, Tracy, additional, Kaazan, Patricia, additional, Lim, Amanda, additional, Marker, Julie, additional, Ostroff, Cheri, additional, Rogers, Geraint, additional, Arpaia, Nicholas, additional, Worthley, Daniel L, additional, Woods, Susan L, additional, and Danino, Tal, additional

Published
2023
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34. Probiotic neoantigen delivery vectors for precision cancer immunotherapy

Author

Redenti, Andrew, Im, Jongwon, Redenti, Benjamin, Li, Fangda, Rouanne, Mathieu, Sheng, Zeren, Sun, William, Gurbatri, Candice R., Huang, Shunyu, Komaranchath, Meghna, Jang, YoungUk, Hahn, Jaeseung, Ballister, Edward R., Vincent, Rosa L., Vardoshivilli, Ana, Danino, Tal, and Arpaia, Nicholas

Abstract

Microbial systems have been synthetically engineered to deploy therapeutic payloads in vivo1,2. With emerging evidence that bacteria naturally home in on tumours3,4and modulate antitumour immunity5,6, one promising application is the development of bacterial vectors as precision cancer vaccines2,7. Here we engineered probiotic Escherichia coliNissle 1917 as an antitumour vaccination platform optimized for enhanced production and cytosolic delivery of neoepitope-containing peptide arrays, with increased susceptibility to blood clearance and phagocytosis. These features enhance both safety and immunogenicity, achieving a system that drives potent and specific T cell-mediated anticancer immunity that effectively controls or eliminates tumour growth and extends survival in advanced murine primary and metastatic solid tumours. We demonstrate that the elicited antitumour immune response involves recruitment and activation of dendritic cells, extensive priming and activation of neoantigen-specific CD4+and CD8+T cells, broader activation of both T and natural killer cells, and a reduction of tumour-infiltrating immunosuppressive myeloid and regulatory T and B cell populations. Taken together, this work leverages the advantages of living medicines to deliver arrays of tumour-specific neoantigen-derived epitopes within the optimal context to induce specific, effective and durable systemic antitumour immunity.

Published
2024
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39. Synchronized cycles of bacterial lysis for in vivo delivery

Author

Din, M. Omar, Danino, Tal, Prindle, Arthur, Skalak, Matt, Selimkhanov, Jangir, Allen, Kaitlin, Julio, Ellixis, Atolia, Eta, Tsimring, Lev S., Bhatia, Sangeeta N., and Hasty, Jeff

Subjects
Cell death -- Analysis, Drugs -- Vehicles, Population biology -- Analysis, Chemotherapy -- Analysis, Cancer -- Chemotherapy, Drug delivery systems -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The widespread view of bacteria as strictly pathogenic has given way to an appreciation of the prevalence of some beneficial microbes within the human body (1-3). It is perhaps inevitable that some bacteria would evolve to preferentially grow in environments that harbour disease and thus provide a natural platform for the development of engineered therapies (4-6). Such therapies could benefit from bacteria that are programmed to limit bacterial growth while continually producing and releasing cytotoxic agents in situ (7-10). Here we engineer a clinically relevant bacterium to lyse synchronously at a threshold population density and to release genetically encoded cargo. Following quorum lysis, a small number of surviving bacteria reseed the growing population, thus leading to pulsatile delivery cycles. We used microfluidic devices to characterize the engineered lysis strain and we demonstrate its potential as a drug delivery platform via co-culture with human cancer cells in vitro. As a proof of principle, we tracked the bacterial population dynamics in ectopic syngeneic colorectal tumours in mice via a luminescent reporter. The lysis strain exhibits pulsatile population dynamics in vivo, with mean bacterial luminescence that remained two orders of magnitude lower than an unmodified strain. Finally, guided by previous findings that certain bacteria can enhance the efficacy of standard therapies (11), we orally administered the lysis strain alone or in combination with a clinical chemotherapeutic to a syngeneic mouse transplantation model of hepatic colorectal metastases. We found that the combination of both circuit-engineered bacteria and chemotherapy leads to a notable reduction of tumour activity along with a marked survival benefit over either therapy alone. Our approach establishes a methodology for leveraging the tools of synthetic biology to exploit the natural propensity for certain bacteria to colonize disease sites., In order to control population levels and facilitate drug delivery using bacteria, we engineered a synchronized lysis circuit (SLC) using coupled positive and negative feedback loops that have previously been [...]

Published
2016

48. A programmable probiotic encapsulation system enhances therapeutic delivery in vivo

Author

Harimoto, Tetsuhiro, primary, Hahn, Jaeseung, additional, Chen, Yu-Yu, additional, Im, Jongwon, additional, Zhang, Joanna, additional, Hou, Nicholas, additional, Li, Fangda, additional, Coker, Courtney, additional, Gray, Kelsey, additional, Harr, Nicole, additional, Chowdhury, Sreyan, additional, Pu, Kelly, additional, Nimura, Clare, additional, Arpaia, Nicholas, additional, Leong, Kam, additional, and Danino, Tal, additional

Published
2021
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50. A sensing array of radically coupled genetic 'biopixels'

Author

Prindle, Arthur, Samayoa, Phillip, Razinkov, Ivan, Danino, Tal, Tsimring, Lev S., and Hasty, Jeff

Subjects
Biosensors -- Research, Synthetic biology -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Although there has been considerable progress in the development of engineering principles for synthetic biology, a substantial challenge is the construction of robust circuits in a noisy cellular environment. Such an environment leads to considerable intercellular variability in circuit behaviour, which can hinder functionality at the colony level. Here we engineer the synchronization of thousands of oscillating colony 'biopixels' over centimetre-length scales through the use of synergistic intercellular coupling involving quorum sensing within a colony and gas-phase redox signalling between colonies. We use this platform to construct a liquid crystal display (LCD)-like macroscopic clock that can be used to sense arsenic via modulation of the oscillatory period. Given the repertoire of sensing capabilities of bacteria such as Escherichia coli, the ability to coordinate their behaviour over large length scales sets the stage for the construction of low cost genetic biosensors that are capable of detecting heavy metals and pathogens in the field., Synthetic biology can be broadly broken down into the 'top-down' synthesis of genomes (1) and the 'bottom-up' engineering of relatively small genetic circuits (2-10). In the field of genetic circuits, [...]

Published
2012
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