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Your search keyword '"Shopsowitz, Kevin E."' showing total 184 results
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184 results on '"Shopsowitz, Kevin E."'

1. Human ASXL1 Deficiency Causes Epigenetic Dysfunction, Combined Immunodeficiency and EBV-Associated Hodgkin Lymphoma

Author

Fu, Maggie P, primary, Sharma, Mehul, additional, Merrill, Sarah M, additional, Yousefi, Pariya, additional, Tan, Ryan, additional, Modi, Bhavi P, additional, Del Bel, Kate, additional, Deyell, Rebecca J, additional, Rozmus, Jacob, additional, Rehmus, Wingfield, additional, Hildebrand, Kyla J, additional, James, Elliot, additional, Blanchard-Rohner, Geraldine, additional, Lin, Susan, additional, Shopsowitz, Kevin E, additional, Setiadi, Audi, additional, Terry, Jefferson, additional, Lee, Anna F, additional, Drogemoller, Britt I, additional, Matthews, Allison, additional, Tarailo-Graovac, Maja, additional, Sauve, Laura, additional, Mitchell, Hana, additional, Prendiville, Julie S, additional, MacIsaac, Julie L, additional, Dever, Kristy, additional, Lin, David TS, additional, Meijer, Mandy, additional, Ross, Colin JD, additional, Dobson, Simon RM, additional, Vercauteren, Suzanne M, additional, Wasserman, Wyeth W, additional, van Karnebeek, Clara DM, additional, McKinnon, Margaret L, additional, Kobor, Michael S, additional, Turvey, Stuart E, additional, and Biggs, Catherine M, additional

Published
2023
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2. Expanding the molecular and phenotypic spectrum of CTLA‐4 insufficiency.

Author

Duke, Sean, Maiarana, James, Yousefi, Pariya, Burks, Elijah, Gerrie, Samantha, Setiadi, Audi, Amid, Ali, Boerkel, Cornelius, Erdle, Stephanie, Guttman, Orlee, Kanani, Amin, Lawrence, Sally, Lee, Anna F., Pourshahnazari, Persia, Rayar, Meera, Rozmus, Jacob, Schrader, Dewi, Sharma, Mehul, Shopsowitz, Kevin E., and Tan, Ryan

Subjects
CYTOTOXIC T lymphocyte-associated molecule-4, MOLECULAR spectra, AUTOIMMUNE diseases, REGULATORY T cells, ADRENAL insufficiency
Abstract

This article explores the molecular and phenotypic aspects of CTLA-4 insufficiency, a rare genetic disorder that affects the immune system. It presents two case studies, one involving a 22-month-old infant and the other a 13-year-old boy, both of whom exhibit different symptoms and outcomes associated with the condition. The article emphasizes the significance of genetic testing in accurately diagnosing and treating CTLA-4 insufficiency. Additionally, it discusses the functional validation of two new variants in the CTLA4 gene and their potential implications for disease progression and treatment. [Extracted from the article]

Published
2024
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5. Enhancing chemotherapy response through augmented synthetic lethality by co-targeting nucleotide excision repair and cell-cycle checkpoints

Author

Kong, Yi Wen, Dreaden, Erik C., Morandell, Sandra, Zhou, Wen, Dhara, Sanjeev S., Sriram, Ganapathy, Lam, Fred C., Patterson, Jesse C., Quadir, Mohiuddin, Dinh, Anh, Shopsowitz, Kevin E., Varmeh, Shohreh, Yilmaz, Ömer H., Lippard, Stephen J., Reinhardt, H. Christian, Hemann, Michael T., Hammond, Paula T., and Yaffe, Michael B.

Published
2020
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7. Human JAK1 gain of function causes dysregulated myelopoeisis and severe allergic inflammation

Author

Biggs, Catherine M., primary, Cordeiro-Santanach, Anna, additional, Prykhozhij, Sergey V., additional, Deveau, Adam P., additional, Lin, Yi, additional, Del Bel, Kate L., additional, Orben, Felix, additional, Ragotte, Robert J., additional, Saferali, Aabida, additional, Mostafavi, Sara, additional, Dinh, Louie, additional, Dai, Darlene, additional, Weinacht, Katja G., additional, Dobbs, Kerry, additional, Ott de Bruin, Lisa, additional, Sharma, Mehul, additional, Tsai, Kevin, additional, Priatel, John J., additional, Schreiber, Richard A., additional, Rozmus, Jacob, additional, Hosking, Martin C.K., additional, Shopsowitz, Kevin E., additional, McKinnon, Margaret L., additional, Vercauteren, Suzanne, additional, Seear, Michael, additional, Notarangelo, Luigi D., additional, Lynn, Francis C., additional, Berman, Jason N., additional, and Turvey, Stuart E., additional

Published
2022
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11. Impacts of COVID‐19 and elective surgery cancellations on platelet supply and utilization in the Canadian Province of British Columbia

Author

Shopsowitz, Kevin E., primary, Lim, Christina, additional, Shih, Andrew W., additional, Fishbane, Nick, additional, Berry, Brian R., additional, Bigham, Mark, additional, Petraszko, Tanya, additional, Trudeau, Jacqueline, additional, Wyatt, Maureen, additional, Yan, Matthew T. S., additional, and Morrison, Douglas, additional

Published
2021
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12. Rational design of multistage drug delivery vehicles for pulmonary RNA interference therapy

Author

Silva, A Sofia, Shopsowitz, Kevin E, Correa, Santiago, Morton, Stephen W, Dreaden, Erik C, Casimiro, Teresa, Aguiar-Ricardo, Ana, Hammond, Paula T, Silva, A Sofia, Shopsowitz, Kevin E, Correa, Santiago, Morton, Stephen W, Dreaden, Erik C, Casimiro, Teresa, Aguiar-Ricardo, Ana, and Hammond, Paula T

Abstract

© 2020 Elsevier B.V. Small interfering RNA (siRNA) therapy has significant potential for the treatment of myriad diseases, including cancer. While intravenous routes of delivery have been found to be effective for efficient targeting to the liver, achieving high accumulations selectively in other organs, including lung tissues, can be a challenge. We demonstrate the rational design and engineering of a layer-by-layer (LbL) nanoparticle-containing aerosol that is able to achieve efficient, multistage delivery of siRNA in vitro. For the purpose, LbL nanoparticles were, for the first time, encapsulated in composite porous micro scale particles using a supercritical CO2-assisted spray drying (SASD) apparatus using chitosan as an excipient. Such particles exhibited aerodynamic properties highly favorable for pulmonary administration, and effective silencing of mutant KRAS in lung cancer cells derived from tumors of a non-small cell lung cancer (NSCLC) autochthonous model. Furthermore, efficient alveolar accumulation following inhalation in healthy mice was also observed, corroborating in vitro aerodynamic results, and opening new perspectives for further studies of effective lung therapies These results show that multistage aerosols assembled by supercritical CO2-assisted spray drying can enable efficient RNA interference therapy of pulmonary diseases including lung cancer.

Published
2021

13. Engineering Periodic shRNA for Enhanced Silencing Efficacy

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies, Wu, Connie, Shopsowitz, Kevin E, Hammond, Paula T, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies, Wu, Connie, Shopsowitz, Kevin E, and Hammond, Paula T

Abstract

RNA interference (RNAi) provides a versatile therapeutic approach via silencing of specific genes, particularly undruggable targets in cancer and other diseases. However, challenges in the delivery of small interfering RNA (siRNA) have hampered clinical translation. Polymeric or periodic short hairpin RNAs (p-shRNAs) - synthesized by enzymatic amplification of circular DNA - are a recent development that can potentially address these delivery barriers by showing improved stability and complexation to enable nanoparticle packaging. Here, we modify these biomacromolecules via structural and sequence engineering coupled with selective enzymatic digestion to generate an open-ended p-shRNA (op-shRNA) that is cleaved over ten times more efficiently to yield siRNA. The op-shRNA induces considerably greater gene silencing than p-shRNA in multiple cancer cell lines up to 9 days. Furthermore, its high valency and flexibility dramatically improve complexation with a low molecular weight polycation compared to monomeric siRNA. Thus, op-shRNA provides an RNAi platform that can potentially be packaged and efficiently delivered to disease sites with higher therapeutic efficacy.

Published
2021

14. Enhancing chemotherapy response through augmented synthetic lethality by co-targeting nucleotide excision repair and cell-cycle checkpoints

Author

Koch Institute for Integrative Cancer Research at MIT, Center for Precision Cancer Medicine, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Biological Engineering, Kong, Yi Wen, Dreaden, Erik C, Morandell, Sandra, Zhou, Wen, Dhara, Sanjeev S, Sriram, Ganapathy, Lam, Fred C, Patterson, Jesse C, Quadir, Mohiuddin, Dinh, Anh, Shopsowitz, Kevin E, Varmeh, Shohreh, Yilmaz, Ömer H, Lippard, Stephen J, Reinhardt, H Christian, Hemann, Michael T, Hammond, Paula T, Yaffe, Michael B, Koch Institute for Integrative Cancer Research at MIT, Center for Precision Cancer Medicine, Massachusetts Institute of Technology. Department of Chemical Engineering, Massachusetts Institute of Technology. Department of Chemistry, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Biological Engineering, Kong, Yi Wen, Dreaden, Erik C, Morandell, Sandra, Zhou, Wen, Dhara, Sanjeev S, Sriram, Ganapathy, Lam, Fred C, Patterson, Jesse C, Quadir, Mohiuddin, Dinh, Anh, Shopsowitz, Kevin E, Varmeh, Shohreh, Yilmaz, Ömer H, Lippard, Stephen J, Reinhardt, H Christian, Hemann, Michael T, Hammond, Paula T, and Yaffe, Michael B

Abstract

© 2020, The Author(s). In response to DNA damage, a synthetic lethal relationship exists between the cell cycle checkpoint kinase MK2 and the tumor suppressor p53. Here, we describe the concept of augmented synthetic lethality (ASL): depletion of a third gene product enhances a pre-existing synthetic lethal combination. We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. Delivery of siRNA-peptide nanoplexes co-targeting MK2 and XPA to pre-existing p53-deficient tumors in a highly aggressive, immunocompetent mouse model of lung adenocarcinoma improves long-term survival and cisplatin response beyond those of the synthetic lethal p53 mutant/MK2 combination alone. These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment.

Published
2021

15. Free-standing mesoporous silica films with tunable chiral nematic structures

Author

Shopsowitz, Kevin E., Qi, Hao, Hamad, Wadood Y., and MacLachlan, Mark J.

Subjects
Chirality -- Research, Molecular structure -- Research, Silica -- Properties -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Chirality at the molecular level is found in diverse biological structures, such as polysaccharides, proteins and DNA, and is responsible for many of their unique properties (1). Introducing chirality into porous inorganic solids may produce new types of materials that could be useful for chiral separation, stereospecific catalysis, chiral recognition (sensing) and photonic materials (2-5). Template synthesis of inorganic solids using the self-assembly of lyotropic liquid crystals offers access to materials with well-defined porous structures (6-12), but only recently has chirality been introduced into hexagonal mesostructures through the use of a chiral surfactant (13,14). Efforts to impart chirality at a larger length scale using self-assembly are almost unknown. Here we describe the development of a photonic mesoporous inorganic solid that is a cast of a chiral nematic liquid crystal formed from nanocrystalline cellulose. These materials may be obtained as free-standing films with high surface area. The peak reflected wavelength of the films can be varied across the entire visible spectrum and into the near-infrared through simple changes in the synthetic conditions. To the best of our knowledge these are the first materials to combine mesoporosity with long-range chiral ordering that produces photonic properties. Our findings could lead to the development of new materials for applications in, for example, tuneable reflective filters and sensors. In addition, this type of material could be used as a hard template to generate other new materials with chiral nematic structures., The chiral nematic (or cholesteric) liquid crystalline phase, in which mesogens are organized in a helical assembly, was first observed for cholesterol derivatives but is now known for a variety [...]

Published
2010
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19. Machine learning optimized multiparameter radar plots for B‐cell acute lymphoblastic leukemiaminimal residual disease analysis

Author

Shopsowitz, Kevin E., Liu, Lorraine, Setiadi, Audi, Al‐Bakri, Maryam, and Vercauteren, Suzanne

Abstract

Flow cytometry is widely used for B‐ALL minimal residual disease (MRD) analysis given its speed, availability, and sensitivity; however, distinguishing B‐lymphoblasts from regenerative B‐cells is not always straightforward. Radar plots, which project multiple markers onto a single plot, have been applied to other MRD analyses. Here we aimed to develop optimized radar plots for B‐ALL MRD analysis. We compiled Children's Oncology Group (COG) flow data from 20 MRD‐positive and 9 MRD‐negative B‐ALL cases (enriched for hematogones) to create labeled training and test data sets with equal numbers of B‐lymphoblasts, hematogones, and mature B‐cells. We used an automated approach to create hundreds of radar plots and ranked them based on the ability of support vector machine (SVM) models to separate blasts from normal B‐cells in the training data set. Top‐performing radar plots were compared with PCA, t‐SNE, and UMAP plots, evaluated with the test data set, and integrated into clinical workflows. SVM area under the ROC curve (AUC) for COG tube 1/2 radar plots improved from 0.949/0.921 to 0.989/0.968 after optimization. Performance was superior to PCA plots and comparable to UMAP, but with better generalizability to new data. When integrated into an MRD workflow, optimized radar plots distinguished B‐lymphoblasts from other CD19‐positive populations. MRD quantified by radar plots and serial gating were strongly correlated. Radar plots were successfully optimized to discriminate between diverse B‐lymphoblast populations and non‐malignant CD19‐positive populations in B‐ALL MRD analysis. Our novel radar plot optimization strategy could be adapted to other MRD panels and clinical scenarios.

Published
2022
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20. Impacts of COVID‐19 and elective surgery cancellations on platelet supply and utilization in the Canadian Province of British Columbia.

Author

Shopsowitz, Kevin E., Lim, Christina, Shih, Andrew W., Fishbane, Nick, Berry, Brian R., Bigham, Mark, Petraszko, Tanya, Trudeau, Jacqueline, Wyatt, Maureen, Yan, Matthew T. S., and Morrison, Douglas

Subjects
*CANADIAN provinces, *ELECTIVE surgery, *BLOOD platelets, *COVID-19, SURGERY practice
Abstract

Background and Objectives: The coronavirus disease 2019 (COVID‐19) pandemic raised concerns about the vulnerability of platelet supply and the uncertain impact of the resumption of elective surgery on utilization. We report the impact of COVID‐19 on platelet supply and utilization across a large, integrated healthcare system in the Canadian province of British Columbia (BC). Materials and Methods: Historical platelet use in BC by indication was compiled for fiscal year 2010/2011–2019/2020. Platelet collections, initial daily inventory and disposition data were assessed pre‐COVID‐19 (1 April 2018–15 March 2020) and for two COVID‐19 time periods in BC: a shutdown phase with elective surgeries halted (16 March–17 May, 2020) and a renewal phase when elective surgeries resumed (18 May–27 September 2020); comparisons were made provincially and for individual health authorities. Results: Historically, elective surgeries accounted for 10% of platelets transfused in BC. Initial daily supplier inventory increased from baseline during both COVID‐19 periods (93/90 units vs. 75 units pre‐COVID‐19). During the shutdown phase, platelet utilization decreased 10.4% (41 units/week; p < 0.0001), and remained significantly decreased during the ensuing renewal period. Decreased platelet utilization was attributed to fewer transfusions during the shutdown phase followed by a decreased discard/expiry rate during the renewal phase compared to pre‐COVID‐19 (15.2% vs. 18.9% pre‐COVID‐19; p < 0.0001). Differences in COVID‐19 platelet utilization patterns were noted between health authorities. Conclusion: Decreased platelet utilization was observed in BC compared to pre‐COVID‐19, likely due to a transient reduction in elective surgery as well as practice and policy changes triggered by pandemic concerns. [ABSTRACT FROM AUTHOR]

Published
2022
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23. RNA‐Peptide nanoplexes drug DNA damage pathways in high‐grade serous ovarian tumors

Author

Dreaden, Erik C., primary, Kong, Yi Wen, additional, Quadir, Mohiuddin A., additional, Correa, Santiago, additional, Suárez‐López, Lucia, additional, Barberio, Antonio E., additional, Hwang, Mun Kyung, additional, Shi, Aria C., additional, Oberlton, Benjamin, additional, Gallagher, Paige N., additional, Shopsowitz, Kevin E., additional, Elias, Kevin M., additional, Yaffe, Michael B., additional, and Hammond, Paula T., additional

Published
2018
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24. Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment

Author

Deng, Zhou J., Morton, Stephen W., Ben-Akiva, Elana, Dreaden, Erik C., Shopsowitz, Kevin E., and Hammond, Paula T.

Abstract

A single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-negative breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-l-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA molecules, and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose viaintravenous administration significantly reduced the target gene expression in the tumors by almost 80%. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold in vitroand led to up to an 8-fold decrease in tumor volume compared to the control treatments with no observed toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system.

Published
2024
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32. Novel PPV/Mesoporous Organosilica Composites : Influence of the Host Chirality on a Conjugated Polymer Guest

Author

Hessam, S., MacLachlan, Mark J., Hamad, Wadood Y., Shopsowitz, Kevin E., Qi, Hao, Giese, Michael R. A., and Mehrt, M.

Subjects
chemistry.chemical_classification, Circular dichroism, Materials science, Chemie, Surfaces and Interfaces, Polymer, Conjugated system, Condensed Matter Physics, Photochemistry, Fluorescence, Mesoporous organosilica, Polymerization, chemistry, Liquid crystal, Polymer chemistry, Electrochemistry, General Materials Science, Chirality (chemistry), Spectroscopy
Abstract

The conjugated polymer poly(p-phenylenevinylene) (PPV) was polymerized in the pores of chiral nematic mesoporous organosilica to give a composite film showing the strong characteristic fluorescence of PPV as well as the iridescence due to the photonic band gap of the host material. Detailed circular dichroism (CD) studies reveal a chiral structure of the polymer within the pores. These new fluorescent materials undergo fluorescence quenching upon exposure to electron deficient aromatics such as 2,4,6-trinitrotoluene (TNT), indicating that they may be useful for developing chemical sensors.

Published
2013

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