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3. Quantification of Ebola virus replication kinetics in vitro

Author

Liao, Laura E., Carruthers, Jonathan, Smither, Sophie J., Team, CL4 Virology, Weller, Simon A., Williamson, Diane, Laws, Thomas R., Garcia-Dorival, Isabel, Hiscox, Julian, Holder, Benjamin P., Beauchemin, Catherine A. A., Perelson, Alan S., Lopez-Garcia, Martin, Lythe, Grant, Barr, John, and Molina-Paris, Carmen

Subjects
Quantitative Biology - Cell Behavior
Abstract

Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic., Comment: 16 pages, 3 figures, to be published in PLOS Computational Biology

Published
2020
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5. Tutorial on agent-based models in NetLogo applied to immunology and virology

Author

Beauchemin, Catherine A. A., Liao, Laura E., and Blahut, Kenneth

Subjects
Quantitative Biology - Quantitative Methods, 92B05
Abstract

This tutorial introduces participants to the design and implementation of an agent-based model using NetLogo through one of two different projects: modelling T cell movement within a lymph node or modelling the progress of a viral infection in an in vitro cell culture monolayer. Each project is broken into a series of incremental steps of increasing complexity. Each step is described in detail and the code to type in is initially provided. However, each project has room to grow in complexity and biological realism so participants are encouraged to expand their project beyond the scope of the tutorial or to develop a project of their own.

Published
2018

9. Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody

Author

Asokan, Mangaiarkarasi, Dias, Joana, Liu, Cuiping, Maximova, Anna, Ernste, Keenan, Pegu, Amarendra, McKee, Krisha, Shi, Wei, Chen, Xuejun, Almasri, Cassandra, Promsote, Wanwisa, Ambrozak, David R., Gama, Lucio, Hu, Jianfei, Douek, Daniel C., Todd, John-Paul, Lifson, Jeffrey D., Fourati, Slim, Sekaly, Rafick P., Crowley, Andrew R., Ackerman, Margaret E., Ko, Sung Hee, Kilam, Divya, Boritz, Eli A., Liao, Laura E., Best, Katharine, Perelson, Alan S., Mascola, John R., and Koup, Richard A.

Published
2020

11. Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1

Author

Romero, Rodrigo, Sánchez-Rivera, Francisco J., Westcott, Peter M. K., Mercer, Kim L., Bhutkar, Arjun, Muir, Alexander, González Robles, Tania J., Lamboy Rodríguez, Swanny, Liao, Laura Z., Ng, Sheng Rong, Li, Leanne, Colón, Caterina I., Naranjo, Santiago, Beytagh, Mary Clare, Lewis, Caroline A., Hsu, Peggy P., Bronson, Roderick T., Vander Heiden, Matthew G., and Jacks, Tyler

Published
2020
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13. Toward Early-Warning Detection of Gravitational Waves from Compact Binary Coalescence

Author

Cannon, Kipp, Cariou, Romain, Chapman, Adrian, Crispin-Ortuzar, Mireia, Fotopoulos, Nickolas, Frei, Melissa, Hanna, Chad, Kara, Erin, Keppel, Drew, Liao, Laura, Privitera, Stephen, Searle, Antony, Singer, Leo, and Weinstein, Alan

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics, General Relativity and Quantum Cosmology
Abstract

Rapid detection of compact binary coalescence (CBC) with a network of advanced gravitational-wave detectors will offer a unique opportunity for multi-messenger astronomy. Prompt detection alerts for the astronomical community might make it possible to observe the onset of electromagnetic emission from (CBC). We demonstrate a computationally practical filtering strategy that could produce early-warning triggers before gravitational radiation from the final merger has arrived at the detectors., Comment: 16 pages, 7 figures, published in ApJ. Reformatted preprint with emulateapj

Published
2011
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14. Clinical outcomes of older and younger patients treated with loncastuximab tesirine in the LOTIS-2 clinical trial

Author

Hamadani, Mehdi, primary, Spira, Alexander, additional, Zhou, Xiaolei, additional, Liao, Laura, additional, Chen, Lei, additional, Radford, John, additional, Ai, Weiyun, additional, Solh, Melhem, additional, Ardeshna, Kirit M., additional, Hess, Brian, additional, Caimi, Paolo F., additional, Stathis, Anastasios, additional, Carlo-Stella, Carmelo, additional, Alderuccio, Juan Pablo, additional, Kahl, Brad, additional, Wang, Ying, additional, Qin, Yajuan, additional, Xu, Zhiying Cindy, additional, and Zinzani, Pier Luigi, additional

Published
2024
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19. Investigation of Relationships between Urinary Biomarkers of Phytoestrogens, Phthalates, and Phenols and Pubertal Stages in Girls

Author

Wolff, Mary S, Teitelbaum, Susan L, Pinney, Susan M, Windham, Gayle, Liao, Laura, Biro, Frank, Kushi, Lawrence H, Erdmann, Chris, Hiatt, Robert A, Rybak, Michael E, Calafat, Antonia M, and Centers, the Breast Cancer and Environment Research

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Clinical Research, Women's Health, Breast Cancer, Cancer, Pediatric, 4.1 Discovery and preclinical testing of markers and technologies, Body Mass Index, California, Child, Chromatography, High Pressure Liquid, Environmental Exposure, Female, Humans, Longitudinal Studies, New York City, Ohio, Phenols, Phthalic Acids, Phytoestrogens, Puberty, Tandem Mass Spectrometry, biomarkers, phenols, phthalates, phytoestrogens, puberty, Breast Cancer and Environment Research Centers, Environmental Sciences, Medical and Health Sciences, Toxicology, Biomedical and clinical sciences, Environmental sciences, Health sciences
Abstract

BackgroundHormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins.ObjectivesWe investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007).MethodsWe measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones.ResultsBreast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88-1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23-1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone.ConclusionsWeak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.

Published
2010

20. Publisher Correction: Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1

Author

Romero, Rodrigo, Sánchez-Rivera, Francisco J., Westcott, Peter M. K., Mercer, Kim L., Bhutkar, Arjun, Muir, Alexander, González Robles, Tania J., Rodríguez, Swanny Lamboy, Liao, Laura Z., Ng, Sheng Rong, Li, Leanne, Colón, Caterina I., Naranjo, Santiago, Beytagh, Mary Clare, Lewis, Caroline A., Hsu, Peggy P., Bronson, Roderick T., Vander Heiden, Matthew G., and Jacks, Tyler

Published
2020
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25. Poster: ABCL-316 Health-Related Quality of Life and Tolerability in Patients With/Without Skin Toxicity During Loncastuximab Tesirine Treatment in a Phase 2 Clinical Trial (LOTIS-2)

Author

Spira, Alexander, primary, Zhou, Xiaolei, additional, Liao, Laura, additional, Yu, Eric, additional, Chen, Lei, additional, Lau, Augustine, additional, Wang, Ying, additional, Gnanasakthy, Ari, additional, Radford, John, additional, and Hamadani, Mehdi, additional

Published
2022
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28. Modeling diverse genetic subtypes of lung adenocarcinoma with a next-generation alveolar type 2 organoid platform

Author

Naranjo, Santiago, primary, Cabana, Christina M., additional, LaFave, Lindsay M., additional, Romero, Rodrigo, additional, Shanahan, Sean-Luc, additional, Bhutkar, Arjun, additional, Westcott, Peter M.K., additional, Schenkel, Jason M., additional, Ghosh, Arkopravo, additional, Liao, Laura Z., additional, Del Priore, Isabella, additional, Yang, Dian, additional, and Jacks, Tyler, additional

Published
2022
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31. HSR22-171: Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Older Versus Younger Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma Treated in a Phase 2 Clinical Trial (LOTIS-2)

Author

Spira, Alexander, primary, Liao, Laura, additional, Zhou, Xiaolei, additional, Sherif, Bintu, additional, Chen, Lei, additional, Ungar, David, additional, Yu, Eric, additional, Radford, John, additional, and Hamadani, Mehdi, additional

Published
2022
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32. Modeling diverse genetic subtypes of lung adenocarcinoma with a next-generation alveolar type 2 organoid platform

Author

Naranjo, Santiago, primary, Cabana, Christina M., additional, LaFave, Lindsay M., additional, Westcott, Peter M.K., additional, Romero, Rodrigo, additional, Ghosh, Arkopravo, additional, Liao, Laura Z., additional, Schenkel, Jason M., additional, Priore, Isabella Del, additional, Bhutkar, Arjun, additional, Yang, Dian, additional, and Jacks, Tyler, additional

Published
2021
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34. Glycaemic control and hypoglycaemia burden in patients with type 2 diabetes initiating basal insulin in Europe and the USA

Author

Mauricio Puente, Dídac, Meneghini, Luigi, Seufert, Jochen, Liao, Laura, Wang, Hongwei, Tong, Liyue, Cali, Anna, Stella, Peter, Carita, Paulo, Khunti, Kamlesh, and Universitat Autònoma de Barcelona

Subjects
Glycaemic control, Basal insulin, Type 2 diabetes, Hypoglycaemia
Abstract

Estudi finançat per Sanofi Aims: To evaluate short- and long-term glycaemic control and hypoglycaemia incidence in insulin-naïve patients ≥30 years of age with type 2 diabetes (T2DM) initiating basal insulin (BI) with or without oral anti-hyperglycaemic drugs (OADs). Methods: This was an observational, retrospective longitudinal analysis of electronic medical records from 5 European countries and the USA. A multivariable logistic regression model assessed baseline and short-term (0-3 months post BI initiation) factors associated with longterm (3-24 months) glycaemic control and hypoglycaemia. Results: Overall, 40 627 patients were included; 20.9% and 27.8% achieved the general HbA1c target of ≤7% at 3 and 24 months post BI initiation, respectively. Failure to achieve HbA1c ≤7% at 3 months was associated with increased risk of failing to achieve target at 24 months (odds ratio [OR], 3.70 [95% CI, 3.41-4.00]). Over 24 months, 8.9% of patients experienced a recorded hypoglycaemic event. Hypoglycaemia during the initial 3-month period was associated with longer-term risk of these events over the ensuing 3 to 24 months (OR, 5.71 [95% CI, 4.67-6.99]). Conclusions: Initiating BI with or without OADs is associated with short- and long-term suboptimal glycaemic control; the majority of patients fail to achieve HbA1c target ≤7% in the first 3 months, or after 2 years of BI treatment. Treatment response and hypoglycaemia incidence by 3 months post BI initiation are associated with longer-term glycaemic control and hypoglycaemic risk, respectively. These results support the need for early anti-hyperglycaemic interventions that more effectively control blood glucose levels without increasing the risk of hypoglycaemia.

Published
2021

36. Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Romero, Rodrigo, Sánchez-Rivera, Francisco J, Westcott, Peter MK, Mercer, Kim L, Bhutkar, Arjun, Muir, Alexander, González Robles, Tania J, Lamboy Rodríguez, Swanny, Liao, Laura Z, Ng, Sheng Rong, Li, Leanne, Colón, Caterina I, Naranjo, Santiago, Beytagh, Mary Clare, Lewis, Caroline A, Hsu, Peggy P, Bronson, Roderick T, Vander Heiden, Matthew G, Jacks, Tyler, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Romero, Rodrigo, Sánchez-Rivera, Francisco J, Westcott, Peter MK, Mercer, Kim L, Bhutkar, Arjun, Muir, Alexander, González Robles, Tania J, Lamboy Rodríguez, Swanny, Liao, Laura Z, Ng, Sheng Rong, Li, Leanne, Colón, Caterina I, Naranjo, Santiago, Beytagh, Mary Clare, Lewis, Caroline A, Hsu, Peggy P, Bronson, Roderick T, Vander Heiden, Matthew G, and Jacks, Tyler

Abstract

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. Approximately 20–30% of human lung adenocarcinomas (LUADs) harbor mutations in Kelch-like ECH-associated protein 1 (KEAP1) that hyperactivate the nuclear factor, erythroid 2-like 2 (NFE2L2) antioxidant program. We previously showed that Kras-driven Keap1-mutant LUAD is highly aggressive and dependent on glutaminolysis. Here we performed a druggable genome CRISPR screen and uncovered a Keap1-mutant-specific dependency on solute carrier family 33 member 1 (Slc33a1), as well as several functionally related genes associated with the unfolded protein response. Genetic and biochemical experiments using mouse and human Keap1-mutant tumor lines, as well as preclinical genetically engineered mouse models, validate Slc33a1 as a robust Keap1-mutant-specific dependency. Furthermore, unbiased genome-wide CRISPR screening identified additional genes related to Slc33a1 dependency. Overall, our study provides a rationale for stratification of patients harboring KEAP1-mutant or NRF2-hyperactivated tumors as likely responders to targeted SLC33A1 inhibition and underscores the value of integrating functional genetic approaches with genetically engineered mouse models to identify and validate genotype-specific therapeutic targets.

Published
2021

38. CD8 Lymphocyte Depletion Enhances the Latency Reversal Activity of the SMAC Mimetic AZD5582 in ART-Suppressed Simian Immunodeficiency Virus-Infected Rhesus Macaques

Author

Mavigner, Maud, primary, Liao, Laura E., additional, Brooks, Alyssa D., additional, Ke, Ruian, additional, Mattingly, Cameron, additional, Schoof, Nils, additional, McBrien, Julia, additional, Carnathan, Diane, additional, Liang, Shan, additional, Vanderford, Thomas H., additional, Paiardini, Mirko, additional, Kulpa, Deanna, additional, Lifson, Jeffrey D., additional, Dunham, Richard M., additional, Easley, Kirk A., additional, Margolis, David M., additional, Perelson, Alan S., additional, Silvestri, Guido, additional, and Chahroudi, Ann, additional

Published
2021
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47. Signalling in single cell wound healing

Author

Liao, Laura

Abstract

A single cell, such as a frog egg, is able to repair injuries by orchestrating a localized signalling response on the plasma membrane. Proteins called Rho GTPases are recruited to, and form patterns around, the wound site. Patterning allows testable hypotheses to be made about the structure of the signalling network. Here, we extend a Rho GTPase signalling model from Simon et al. (2013) to test how a family of enzymes, protein kinase C (PKC), plays a role in cell repair signalling. Our models let PKCs affect basal Rho GTPase activation and/or inactivation rates, with increasing spatial detail. Ultimately, the model variants do not account for Rho GTPase patterning in all experiments. We suggest a new round of modelling and experiments to correct these issues.

Published
2013
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