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1,805 results on '"Rubin, Eric"'

1. Engineered Mycobacterium tuberculosis triple-kill-switch strain provides controlled tuberculosis infection in animal models

Author

Wang, Xin, Su, Hongwei, Wallach, Joshua B., Wagner, Jeffrey C., Braunecker, Benjamin J., Gardner, Michelle, Guinn, Kristine M., Howard, Nicole C., Klevorn, Thais, Lin, Kan, Liu, Yue J., Liu, Yao, Mugahid, Douaa, Rodgers, Mark, Sixsmith, Jaimie, Wakabayashi, Shoko, Zhu, Junhao, Zimmerman, Matthew, Dartois, Véronique, Flynn, JoAnne L., Lin, Philana Ling, Ehrt, Sabine, Fortune, Sarah M., Rubin, Eric J., and Schnappinger, Dirk

Published
2025
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5. Reducing the risks of nuclear war—the role of health professionals

Author

Abbasi, Kamran, Ali, Parveen, Barbour, Virginia, Bibbins-Domingo, Kirsten, Olde Rikkert, Marcel G. M., Haines, Andy, Helfand, Ira, Horton, Richard, Mash, Bob, Mitra, Arun, Monteiro, Carlos, Naumova, Elena N., Rubin, Eric J., Ruff, Tilman, Sahni, Peush, Tumwine, James, Yonga, Paul, and Zielinski, Chris

Published
2024
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7. Reducing the risks of nuclear war—the role of health professionals

Author

Abbasi, Kamran, Ali, Parveen, Barbour, Virginia, Bibbins-Domingo, Kirsten, Rikkert, Marcel GM Olde, Haines, Andy, Helfand, Ira, Horton, Richard, Mash, Bob, Mitra, Arun, Monteiro, Carlos, Naumova, Elena N., Rubin, Eric J., Ruff, Tilman, Sahni, Peush, Tumwine, James, Yonga, Paul, and Zielinski, Chris

Published
2023

15. Call For Emergency Action to Limit Global Temperature Increases, Restore Biodiversity, and Protect Health Wealthy nations must do much more, much faster

Author

Atwoli, Lukoye, Baqui, Abdullah H., Benfield, Thomas, Bosurgi, Raffaella, Godlee, Fiona, Hancocks, Stephen, Horton, Richard, Laybourn-Langton, Laurie, Monteiro, Carlos Augusto, Norman, Ian, Patrick, Kirsten, Praities, Nigel, Rikkert, Marcel G.M. Olde, Rubin, Eric J., Sahni, Peush, Smith, Richard, Talley, Nick, Turale, Sue, and Vázquez, Damián

Published
2021

17. Chemical–genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy

Author

Koh, Eun-Ik, Oluoch, Peter O., Ruecker, Nadine, Proulx, Megan K., Soni, Vijay, Murphy, Kenan C., Papavinasasundaram, Kadamba, Reames, Charlotte J., Trujillo, Carolina, Zaveri, Anisha, Zimmerman, Matthew D., Aslebagh, Roshanak, Baker, Richard E., Shaffer, Scott A., Guinn, Kristine M., Fitzgerald, Michael, Dartois, Véronique, Ehrt, Sabine, Hung, Deborah T., Ioerger, Thomas R., Rubin, Eric J., Rhee, Kyu Y., Schnappinger, Dirk, and Sassetti, Christopher M.

Published
2022

24. Inflammation unites diverse acute and chronic diseases.

Author

Libby, Peter, Smith, Robin, Rubin, Eric J., Glassberg, Marilyn K., Farkouh, Michael E., and Rosenson, Robert S.

Subjects
ACUTE diseases, LUNG diseases, PHARMACEUTICAL industry, CHRONIC diseases, CARDIOVASCULAR diseases
Abstract

Background: Inflammation and immunity contribute pivotally to diverse acute and chronic diseases. Inflammatory pathways have become increasingly targets for therapy. Yet, despite substantial similarity in mechanisms and pathways, the scientific, medical, pharma and biotechnology sectors have generally focused programs finely on a single disease entity or organ system. This insularity may impede progress in innovation and the harnessing of powerful new insights into inflammation biology ripe for clinical translation. Methods: A multidisciplinary thinktank reviewed highlights how inflammation contributes to diverse diseases, disturbed homeostasis, ageing and impaired healthspan. We explored how common inflammatory and immune mechanisms that operate in key conditions in their respective domains. This consensus review highlights the high degree of commonality of inflammatory mechanisms in a diverse array of conditions that together contribute a major part of the global burden of morbidity and mortality and present an enormous challenge to public health and drain on resources. Results: We demonstrate how that shared inflammatory mechanisms unite many seemingly disparate diseases, both acute and chronic. The examples of infection, cardiovascular conditions, pulmonary diseases, rheumatological disorders, dementia, cancer and ageing illustrate the overlapping pathogenesis. We outline opportunities to synergize, reduce duplication and consolidate efforts of the clinical, research and pharmaceutical communities. Enhanced recognition of these commonalties should promote cross‐fertilization and hasten progress in this rapidly moving domain. Conclusions: Greater appreciation of the shared mechanisms should simplify understanding seemingly disparate diseases for clinicians and help them to recognize inflammation as a therapeutic target which the development of novel therapies is rendering actionable. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Development of MK-8353, an orally administered ERK1/2 inhibitor, in patients with advanced solid tumors

Author

Moschos, Stergios J, Sullivan, Ryan J, Hwu, Wen-Jen, Ramanathan, Ramesh K, Adjei, Alex A, Fong, Peter C, Shapira-Frommer, Ronnie, Tawbi, Hussein A, Rubino, Joseph, Rush, Thomas S, Zhang, Da, Miselis, Nathan R, Samatar, Ahmed A, Chun, Patrick, Rubin, Eric H, Schiller, James, Long, Brian J, Dayananth, Priya, Carr, Donna, Kirschmeier, Paul, Bishop, W Robert, Deng, Yongqi, Cooper, Alan, Shipps, Gerald W, Moreno, Blanca Homet, Robert, Lidia, Ribas, Antoni, and Flaherty, Keith T

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Digestive Diseases, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, 5.1 Pharmaceuticals, Administration, Oral, Adult, Animals, Biological Availability, Cell Line, Tumor, Diarrhea, Dogs, Dose-Response Relationship, Drug, Drug Eruptions, Drug Evaluation, Preclinical, Fatigue, Female, Humans, Indazoles, MAP Kinase Signaling System, Male, Maximum Tolerated Dose, Mice, Middle Aged, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Nausea, Neoplasm Staging, Neoplasms, Protein Kinase Inhibitors, Pyridines, Pyrrolidines, Rats, Triazoles, Xenograft Model Antitumor Assays, Young Adult, Clinical Trials, Melanoma, Oncology, Signal transduction, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundConstitutive activation of ERK1/2 occurs in various cancers, and its reactivation is a well-described resistance mechanism to MAPK inhibitors. ERK inhibitors may overcome the limitations of MAPK inhibitor blockade. The dual mechanism inhibitor SCH772984 has shown promising preclinical activity across various BRAFV600/RAS-mutant cancer cell lines and human cancer xenografts.MethodsWe have developed an orally bioavailable ERK inhibitor, MK-8353; conducted preclinical studies to demonstrate activity, pharmacodynamic endpoints, dosing, and schedule; completed a study in healthy volunteers (P07652); and subsequently performed a phase I clinical trial in patients with advanced solid tumors (MK-8353-001). In the P07652 study, MK-8353 was administered as a single dose in 10- to 400-mg dose cohorts, whereas in the MK-8353-001 study, MK-8353 was administered in 100- to 800-mg dose cohorts orally twice daily. Safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity were analyzed.ResultsMK-8353 exhibited comparable potency with SCH772984 across various preclinical cancer models. Forty-eight patients were enrolled in the P07652 study, and twenty-six patients were enrolled in the MK-8353-001 study. Adverse events included diarrhea (44%), fatigue (40%), nausea (32%), and rash (28%). Dose-limiting toxicity was observed in the 400-mg and 800-mg dose cohorts. Sufficient exposure to MK-8353 was noted that correlated with biological activity in preclinical data. Three of fifteen patients evaluable for treatment response in the MK-8353-001 study had partial response, all with BRAFV600-mutant melanomas.ConclusionMK-8353 was well tolerated up to 400 mg twice daily and exhibited antitumor activity in patients with BRAFV600-mutant melanoma. However, antitumor activity was not particularly correlated with pharmacodynamic parameters.Trial registrationClinicalTrials.gov NCT01358331.FundingMerck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., and NIH (P01 CA168585 and R35 CA197633).

Published
2018

27. Spatiotemporal localization of proteins in mycobacteria

Author

Zhu, Junhao, Wolf, Ian D., Dulberger, Charles L., Won, Harim I., Kester, Jemila C., Judd, Julius A., Wirth, Samantha E., Clark, Ryan R., Li, Yawei, Luo, Yuan, Gray, Todd A., Wade, Joseph T., Derbyshire, Keith M., Fortune, Sarah M., and Rubin, Eric J.

Published
2021
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30. From Famine to Feast: Developing Early-Phase Combination Immunotherapy Trials Wisely

Author

Day, Daphne, Monjazeb, Arta M, Sharon, Elad, Ivy, S Percy, Rubin, Eric H, Rosner, Gary L, and Butler, Marcus O

Subjects
Clinical Research, Cancer, Vaccine Related, Clinical Trials and Supportive Activities, Immunization, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Clinical Trials as Topic, Combined Modality Therapy, Humans, Immunotherapy, Neoplasms, Treatment Outcome, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Not until the turn of this century has immunotherapy become a fundamental component of cancer treatment. While monotherapy with immune modulators, such as immune checkpoint inhibitors, provides a subset of patients with durable clinical benefit and possible cure, combination therapy offers the potential for antitumor activity in a greater number of patients. The field of immunology has provided us with a plethora of potential molecules and pathways to target. This abundance makes it impractical to empirically test all possible combinations efficiently. We recommend that potential immunotherapy combinations be chosen based on sound rationale and available data to address the mechanisms of primary and acquired immune resistance. Novel trial designs may increase the proportion of patients receiving potentially efficacious treatments and, at the same time, better define the balance of clinical activity and safety. We believe that implementing a strategic approach in the early development of immunotherapy combinations will expedite the delivery of more effective therapies with improved safety and durable outcomes.

Published
2017

31. The Tuberculosis Drug Accelerator at year 10: what have we learned?

Author

Aldridge, Bree B., Barros-Aguirre, David, Barry, III, Clifton E., Bates, Robert H., Berthel, Steven J., Boshoff, Helena I., Chibale, Kelly, Chu, Xin-Jie, Cooper, Christopher B., Dartois, Véronique, Duncan, Ken, Fotouhi, Nader, Gusovsky, Fabian, Hipskind, Philip A., Kempf, Dale J., Lelièvre, Joël, Lenaerts, Anne J., McNamara, Case W., Mizrahi, Valerie, Nathan, Carl, Olsen, David B., Parish, Tanya, Petrassi, H. Michael, Pym, Alexander, Rhee, Kyu Y., Robertson, Gregory T., Rock, Jeremy Michael, Rubin, Eric J., Russell, Betsy, Russell, David G., Sacchettini, James C., Schnappinger, Dirk, Schrimpf, Michael, Upton, Anna M., Warner, Peter, Wyatt, Paul Graham, and Yuan, Ying

Published
2021
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33. Mapping the Ultrasound Landscape to Define Point-of-Care Ultrasound and Diagnostic Ultrasound: A Proposal From the Society of Radiologists in Ultrasound and ACR Commission on Ultrasound

Author

Patel, Maitray D., Horrow, Mindy M., Kamaya, Aya, Frates, Mary C., Dahiya, Nirvikar, Golding, Lauren, Chong, Wui K., Gerena, Marielia, Ghate, Sujata, Glanc, Phyllis, Goldbach, Alyssa R., Gupta, Sonia, Hill, Paul A., Johnson, Stephen I., Kocher, Madison R., Rubin, Eric, Sohaey, Roya, Waltz, Jeffrey T., Wolfman, Darcy J., and Middleton, William D.

Published
2021
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38. Call for emergency action to limit global temperature increases, restore biodiversity, and protect health

Author

Atwoli Lukoye, Baqui Abdullah H., Benfield Thomas, Bosurgi Raffaella, Godlee Fiona, Hancocks Stephen, Horton Richard, Laybourn-Langton Laurie, Monteiro Carlos Augusto, Norman Ian, Patrick Kirsten, Praities Nigel, Olde Rikkert Marcel GM, Rubin Eric J., Sahni Peush, Smith Richard, Talley Nick, Turale Sue, and Vázquez Damián

Subjects
Diseases of the respiratory system, RC705-779
Published
2021
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39. Proceedings From the ASCO/College of American Pathologists Immune Checkpoint Inhibitor Predictive Biomarker Summit

Author

Hayes, Daniel F., Herbst, Roy S., Myles, Jonathan L., Topalian, Suzanne L., Yohe, Sophia L., Aronson, Naomi, Bellizzi, Andrew M., Basu Roy, Upal, Bradshaw, Georganne, Edwards, Robin H., El-Gabry, Ehab A., Elvin, Julia, Gajewski, Thomas F., McShane, Lisa M., Oberley, Matthew, Philip, Reena, Rimm, David L., Rosenbaum, Jason N., Rubin, Eric H., Schlager, Lisa, Sherwood, Shimere W., Stewart, Mark, Taube, Janis M., Thurin, Magdalena, Vasalos, Patricia, and Laser, Jordan

Published
2022
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40. Mycobacterium tuberculosis FtsX extracellular domain activates the peptidoglycan hydrolase, RipC

Author

Mavrici, Daniela, Marakalala, Mohlopheni J, Holton, James M, Prigozhin, Daniil M, Gee, Christine L, Zhang, Yanjia J, Rubin, Eric J, and Alber, Tom

Subjects
Biochemistry and Cell Biology, Biological Sciences, Rare Diseases, Genetics, Emerging Infectious Diseases, Tuberculosis, Infectious Diseases, 2.2 Factors relating to the physical environment, Good Health and Well Being, Amino Acid Substitution, Bacterial Proteins, Binding Sites, Cell Cycle Proteins, Cell Wall, Crystallography, X-Ray, Enzyme Activation, Hydrolysis, Mycobacterium smegmatis, Mycobacterium tuberculosis, N-Acetylmuramoyl-L-alanine Amidase, Phenotype, Protein Conformation, Protein Structure, Tertiary, Signal Transduction, Virulence Factors, bacterial cell wall, extracellular signaling, divisome, long-range conformational change
Abstract

Bacterial growth and cell division are coordinated with hydrolysis of the peptidoglycan (PG) layer of the cell wall, but the mechanisms of regulation of extracellular PG hydrolases are not well understood. Here we report the biochemical, structural, and genetic analysis of the Mycobacterium tuberculosis homolog of the transmembrane PG-hydrolase regulator, FtsX. The purified FtsX extracellular domain binds the PG peptidase Rv2190c/RipC N-terminal segment, causing a conformational change that activates the enzyme. Deletion of ftsEX and ripC caused similar phenotypes in Mycobacterium smegmatis, as expected for genes in a single pathway. The crystal structure of the FtsX extracellular domain reveals an unprecedented fold containing two lobes connected by a flexible hinge. Mutations in the hydrophobic cleft between the lobes reduce RipC binding in vitro and inhibit FtsX function in M. smegmatis. These studies suggest how FtsX recognizes RipC and support a model in which a conformational change in FtsX links the cell division apparatus with PG hydrolysis.

Published
2014

43. Informing the Tolerability of Cancer Treatments Using Patient-Reported Outcome Measures: Summary of an FDA and Critical Path Institute Workshop

Author

Kluetz, Paul G., Kanapuru, Bindu, Lemery, Steven, Johnson, Laura Lee, Fiero, Mallorie H., Arscott, Karen, Barbachano, Yolanda, Basch, Ethan, Campbell, Michelle, Cappelleri, Joseph C., Cella, David, Cleeland, Charles, Coens, Corneel, Daniels, Selena, Denlinger, Crystal S., Fairclough, Dianne L., Hillard, James R., Minasian, Lori, Mitchell, Sandra A., O’Connor, Daniel, Patel, Sheetal, Rubin, Eric H., Ryden, Anna, Soltys, Katherine, Sridhara, Rajeshwari, Thanarajasingam, Gita, Velikova, Galina, and Coons, Stephen Joel

Published
2018
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45. Call for emergency action to limit global temperature increases, restore biodiversity and protect health.

Author

Atwoli, Lukoye, Baqui, Abdullah H., Benfield, Thomas, Bosurgi, Raffaella, Godlee, Fiona, Hancocks, Stephen, Horton, Richard, Laybourn Langton, Laurie, Monteiro, Carlos Augusto, Norman, Ian, Patrick, Kirsten, Praities, Nigel, Olde Rikkert, Marcel G. M., Rubin, Eric J., Sahni, Peush, Smith, Richard, Talley, Nicholas J., Turale, Sue, and Vázquez, Damián

Published
2024
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46. Mycobacterium tuberculosis releases an antacid that remodels phagosomes

Author

Buter, Jeffrey, Cheng, Tan-Yun, Ghanem, Marwan, Grootemaat, Anita E., Raman, Sahadevan, Feng, Xinxin, Plantijn, Ashmir R., Ennis, Thomas, Wang, Joyce, Cotton, Rachel N., Layre, Emilie, Ramnarine, Alexandrea K., Mayfield, Jacob A., Young, David C., Jezek Martinot, Amanda, Siddiqi, Noman, Wakabayashi, Shoko, Botella, Helene, Calderon, Roger, Murray, Megan, Ehrt, Sabine, Snider, Barry B., Reed, Michael B., Oldfield, Eric, Tan, Shumin, Rubin, Eric J., Behr, Marcel A., van der Wel, Nicole N., Minnaard, Adriaan J., and Moody, D. Branch

Published
2019
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47. Large-scale chemical–genetics yields new M. tuberculosis inhibitor classes

Author

Johnson, Eachan O., LaVerriere, Emily, Office, Emma, Stanley, Mary, Meyer, Elisabeth, Kawate, Tomohiko, Gomez, James E., Audette, Rebecca E., Bandyopadhyay, Nirmalya, Betancourt, Natalia, Delano, Kayla, Da Silva, Israel, Davis, Joshua, Gallo, Christina, Gardner, Michelle, Golas, Aaron J., Guinn, Kristine M., Kennedy, Sofia, Korn, Rebecca, McConnell, Jennifer A., Moss, Caitlin E., Murphy, Kenan C., Nietupski, Raymond M., Papavinasasundaram, Kadamba G., Pinkham, Jessica T., Pino, Paula A., Proulx, Megan K., Ruecker, Nadine, Song, Naomi, Thompson, Matthew, Trujillo, Carolina, Wakabayashi, Shoko, Wallach, Joshua B., Watson, Christopher, Ioerger, Thomas R., Lander, Eric S., Hubbard, Brian K., Serrano-Wu, Michael H., Ehrt, Sabine, Fitzgerald, Michael, Rubin, Eric J., Sassetti, Christopher M., Schnappinger, Dirk, and Hung, Deborah T.

Published
2019
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