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7 results on '"Jasmin Joseph-Chazan"'

1. Single-cell RNA sequencing of liver fine-needle aspirates captures immune diversity in the blood and liver in chronic hepatitis B patients

Author

Alex S. Genshaft, Sonu Subudhi, Arlin Keo, Juan Diego Sanchez Vasquez, Nádia Conceição-Neto, Deeqa Mahamed, Lauke L. Boeijen, Nadia Alatrakchi, Chris Oetheimer, Mike Vilme, Riley Drake, Ira Fleming, Nancy Tran, Constantine Tzouanas, Jasmin Joseph-Chazan, Martin Arreola Villanueva, Harmen J. G. van de Werken, Gertine W. van Oord, Zwier M.A. Groothuismink, Boris J. Beudeker, Zgjim Osmani, Shirin Nkongolo, Aman Mehrotra, Kurt Spittaels, Jordan Feld, Raymond T. Chung, Robert J. de Knegt, Harry L. A. Janssen, Jeroen Aerssens, Jacques Bollekens, Nir Hacohen, Georg M. Lauer, Andre Boonstra, Alex K. Shalek, and Adam J. Gehring

Subjects
Hepatology
Published
2023

2. Data from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

David T. Ting, Benjamin D. Greenbaum, Peter J. Park, Kathleen H. Burns, David R. Walt, Shelley L. Berger, Theodore S. Hong, Martin J. Aryee, Miguel N. Rivera, Vikram Deshpande, Ryan B. Corcoran, David P. Ryan, Jennifer Y. Wo, Lipika Goyal, Jeffrey W. Clark, Lawrence S. Blaszkowsky, Jill N. Allen, Hui Zheng, Yasmeen Senussi, Padric M. Garden, Limor Cohen, Vishal Thapar, Matteo Ligorio, Kshitij S. Arora, Niyati Desai, Linda T. Nieman, Michael J. Raabe, Jasmin Joseph-Chazan, Chenyue Lu, Eric C. Tai, Kevin D. Vo, Emily E. Van Seventer, Richard Y. Ebright, Nova Xu, Antuan V. Tran, Stefanie Gerstberger, Annamaria Szabolcs, Charly R. Good, Katherine A. Alexander, Connie Wu, Martin S. Taylor, Christopher Jaicks, Katherine H. Xu, Chong Chu, Anupriya S. Kulkarni, Eunae You, Alexander Solovyov, Aparna R. Parikh, and Mihir Rajurkar

Abstract

Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.Significance:Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy.This article is highlighted in the In This Issue feature, p. 1397

Published
2023

3. Supplementary Figure from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

David T. Ting, Benjamin D. Greenbaum, Peter J. Park, Kathleen H. Burns, David R. Walt, Shelley L. Berger, Theodore S. Hong, Martin J. Aryee, Miguel N. Rivera, Vikram Deshpande, Ryan B. Corcoran, David P. Ryan, Jennifer Y. Wo, Lipika Goyal, Jeffrey W. Clark, Lawrence S. Blaszkowsky, Jill N. Allen, Hui Zheng, Yasmeen Senussi, Padric M. Garden, Limor Cohen, Vishal Thapar, Matteo Ligorio, Kshitij S. Arora, Niyati Desai, Linda T. Nieman, Michael J. Raabe, Jasmin Joseph-Chazan, Chenyue Lu, Eric C. Tai, Kevin D. Vo, Emily E. Van Seventer, Richard Y. Ebright, Nova Xu, Antuan V. Tran, Stefanie Gerstberger, Annamaria Szabolcs, Charly R. Good, Katherine A. Alexander, Connie Wu, Martin S. Taylor, Christopher Jaicks, Katherine H. Xu, Chong Chu, Anupriya S. Kulkarni, Eunae You, Alexander Solovyov, Aparna R. Parikh, and Mihir Rajurkar

Abstract

Supplementary Figure from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Published
2023

4. Supplementary Data from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

David T. Ting, Benjamin D. Greenbaum, Peter J. Park, Kathleen H. Burns, David R. Walt, Shelley L. Berger, Theodore S. Hong, Martin J. Aryee, Miguel N. Rivera, Vikram Deshpande, Ryan B. Corcoran, David P. Ryan, Jennifer Y. Wo, Lipika Goyal, Jeffrey W. Clark, Lawrence S. Blaszkowsky, Jill N. Allen, Hui Zheng, Yasmeen Senussi, Padric M. Garden, Limor Cohen, Vishal Thapar, Matteo Ligorio, Kshitij S. Arora, Niyati Desai, Linda T. Nieman, Michael J. Raabe, Jasmin Joseph-Chazan, Chenyue Lu, Eric C. Tai, Kevin D. Vo, Emily E. Van Seventer, Richard Y. Ebright, Nova Xu, Antuan V. Tran, Stefanie Gerstberger, Annamaria Szabolcs, Charly R. Good, Katherine A. Alexander, Connie Wu, Martin S. Taylor, Christopher Jaicks, Katherine H. Xu, Chong Chu, Anupriya S. Kulkarni, Eunae You, Alexander Solovyov, Aparna R. Parikh, and Mihir Rajurkar

Abstract

Supplementary Data from Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Published
2023

5. Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer

Author

Mihir Rajurkar, Aparna R. Parikh, Alexander Solovyov, Eunae You, Anupriya S. Kulkarni, Chong Chu, Katherine H. Xu, Christopher Jaicks, Martin S. Taylor, Connie Wu, Katherine A. Alexander, Charly R. Good, Annamaria Szabolcs, Stefanie Gerstberger, Antuan V. Tran, Nova Xu, Richard Y. Ebright, Emily E. Van Seventer, Kevin D. Vo, Eric C. Tai, Chenyue Lu, Jasmin Joseph-Chazan, Michael J. Raabe, Linda T. Nieman, Niyati Desai, Kshitij S. Arora, Matteo Ligorio, Vishal Thapar, Limor Cohen, Padric M. Garden, Yasmeen Senussi, Hui Zheng, Jill N. Allen, Lawrence S. Blaszkowsky, Jeffrey W. Clark, Lipika Goyal, Jennifer Y. Wo, David P. Ryan, Ryan B. Corcoran, Vikram Deshpande, Miguel N. Rivera, Martin J. Aryee, Theodore S. Hong, Shelley L. Berger, David R. Walt, Kathleen H. Burns, Peter J. Park, Benjamin D. Greenbaum, and David T. Ting

Subjects
Life Cycle Stages, Oncology, Lamivudine, Animals, Humans, RNA, RNA-Directed DNA Polymerase, DNA, Interferons, Tumor Suppressor Protein p53, Colorectal Neoplasms, Antiviral Agents, Article
Abstract

Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.Significance:Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy.This article is highlighted in the In This Issue feature, p. 1397

Published
2022

6. Clinical implementation of single-cell RNA sequencing using liver fine needle aspirate tissue sampling and centralized processing captures compartment specific immuno-diversity

Author

Gertine W. van Oord, Jasmin Joseph-Chazan, Raymond T. Chung, Jordan J. Feld, Juan D. Sanchez Vasquez, Chris Oetheimer, Martin Arreola Villanueva, Ira Fleming, Nir Hacohen, Alex S. Genshaft, Georg M. Lauer, Nancy Tran, Sonu Subudhi, Alex K. Shalek, Jacques Bollekens, Lauke L. Boeijen, Nadia Conceição-Neto, Aman Mehrotra, Adam J. Gehring, Nadia Alatrakchi, Arlin Keo, Constantine Tzouanas, Boris J. B. Beudeker, Zgjim Osmani, Robert J. de Knegt, Mike Vilme, Jeroen Aerssens, Harmen J.G. van de Werken, Harry L.A. Janssen, Shirin Nkongolo, Deeqa Mahamed, Andre Boonstra, Zwier M. A. Groothuismink, and Riley Drake

Subjects
Cell type, medicine.anatomical_structure, Immune system, Immunity, Cell, medicine, RNA, Compartment (development), Computational biology, Biology, Viral hepatitis, medicine.disease, Fine-needle aspirate
Abstract

Blood samples are frequently collected in human studies of the immune system but poorly represent tissue-resident immunity. Understanding the immunopathogenesis of tissue-restricted diseases, such as chronic hepatitis B, necessitates direct investigation of local immune responses. We developed a workflow that enables frequent, minimally invasive collection of liver fine-needle aspirates in multi-site international studies and centralized single-cell RNA sequencing data generation using the Seq-Well S3 picowell-based technology. All immunological cell types were captured, including liver macrophages, and showed distinct compartmentalization and transcriptional profiles, providing a systematic assessment of the capabilities and limitations of peripheral blood samples when investigating tissue-restricted diseases. The ability to electively sample the liver of chronic viral hepatitis patients and generate high-resolution data will enable multi-site clinical studies to power fundamental and therapeutic discovery.

Published
2021

7. Clinical Implementation of Single-Cell RNA Sequencing Using Liver Fine Needle Aspirate Tissuesampling and Centralized Processing Captures Compartment Specific Immuno-Diversity

Author

Alex S. Genshaft, Sonu Subudhi, Arlin Keo, Juan D. Sanchez Vasquez, Nádia Conceição-Neto, Deeqa Mahamed, Lauke L. Boeijen, Nadia Alatrakchi, Chris Oetheimer, Mike Vilme, Riley Drake, Ira Fleming, Nancy Tran, Constantine Tzouanas, Jasmin Joseph-Chazan, Martin Arreola Villanueva, Harmen J. G. van de Werken, Gertine W. van Oord, Zwier M.A. Groothuismink, Boris J. Beudeker, Zgjim Osmani, Shirin Nkongolo, Aman Mehrotra, Jordan Feld, Raymond T. Chung, Robert J. de Knegt, Harry L.A. Janssen, Jeroen Aerssens, Jacques Bollekens, Nir Hacohen, Georg M. Lauer, Andre Boonstra, Alex Shalek, and Adam J. Gehring

Subjects
History, Polymers and Plastics, Business and International Management, Industrial and Manufacturing Engineering
Published
2021

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