Article
Biology
Lev Brio, Danit Wasserman, Efrat Michaely-Barbiro, Gal Barazany-Gal, Doron Gerber, Amit Tzur
Summary: Protein degradation mediated by the ubiquitin-proteasome pathway plays a crucial role in regulating signaling events. In vitro degradation assays, although laborious, have been important in understanding cell proliferation and other cellular processes. We present a microfluidic technology called protein degradation on chip (pDOC) that enables quick and simultaneous protein degradation assays using minute amounts of reagents. This technology offers a sensitive and high-throughput alternative to conventional degradation assays.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Chen Sun, Ming Bai, Weiwei Ke, Xiaoxun Wang, Xiangxuan Zhao, Zaiming Lu
Summary: The study demonstrated that XL888 can promote apoptosis of HCC cells induced by heat both in vitro and in vivo by affecting the expression of relevant proteins. This suggests a potential new combination strategy to enhance the efficiency of RFA.
Article
Engineering, Environmental
Yuanyuan Wang, Fengbang Wang, Zihan Chen, Maoyong Song, Xinglei Yao, Guibin Jiang
Summary: In this study, a high-throughput single-cell imaging method was used to investigate the crosstalk among quantum dot-induced ROS generation, apoptosis, and changes in nucleus size in macrophages. Results indicated a positive correlation between changes in nucleus size and ROS generation, with QDot exposure leading to ROS generation, cell apoptosis, and subsequent changes in nucleus size. These findings provide detailed insights into the heterogeneity of nanoparticle exposure in cellular responses.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Review
Chemistry, Analytical
Majood Haddad, Alex N. Frickenstein, Stefan Wilhelm
Summary: Understanding nanoparticle-cell interactions at single-nanoparticle and single-cell resolutions is crucial to improving the design of next-generation nanoparticles for safer, more effective, and more efficient applications in nanomedicine. This review focuses on recent advances in the continuous high-throughput analysis of nanoparticle-cell interactions at the single-cell level, discussing methods such as flow cytometry and inductively coupled plasma mass spectrometry, as well as their intersection in mass cytometry. The review also explores the challenges and opportunities in current single-cell analysis approaches and proposes directions for innovation in high-throughput analysis of nanoparticle-cell interactions.
TRAC-TRENDS IN ANALYTICAL CHEMISTRY
(2023)
Article
Biology
Chun-Te Chiang, Roy Lau, Ahmadreza Ghaffarizadeh, Matthew Brovold, Dipen Vyas, Edwin F. Juarez, Anthony Atala, David B. Agus, Shay Soker, Paul Macklin, Daniel Ruderman, Shannon M. Mumenthaler
Summary: Quantitative imaging dataset of CRC cell growth dynamics influenced by in vivo-mimicking conditions was presented, showing that highly aggressive HCT116 cell growth is affected by oxygen, substrate stiffness, and liver extracellular matrix. Hypoxia has a protective effect against oxaliplatin-induced cytotoxicity on plastic and liver extracellular matrix. Insights provided by this dataset contribute to understanding critical tumor microenvironment features that influence metastatic seeding and tumor growth.
Article
Chemistry, Analytical
Gerjen H. Tinnevelt, Kristiaan Wouters, Geert J. Postma, Rita Folcarelli, Jeroen J. Jansen
Summary: White blood cells play a crucial role in protecting the body from diseases, but can also be related to chronic inflammation, auto immune diseases, or leukemia. High-throughput analytical instruments have been developed to measure multiple proteins on millions of single cells to study the identity and function of different white blood cell types. Multivariate statistics are essential for fully extracting the information-rich biochemistry data. The process involves analyzing the study design, formulating a research question, preparing the data, converting single cells into a cellular distribution, and using clustering methods or models for analysis to differentiate cell (sub)types between groups.
ANALYTICA CHIMICA ACTA
(2021)
Article
Biochemical Research Methods
Shujie Yang, Joseph Rufo, Ruoyu Zhong, Joseph Rich, Zeyu Wang, Luke P. P. Lee, Tony Jun Huang
Summary: Acoustic tweezers offer an efficient and contact-free way to manipulate individual cells and particles. Its application in next-generation cellular assays can enhance our understanding of biological systems. With acoustic tweezers, users can conduct a variety of experiments involving trapping, patterning, pairing, and separating single cells in the field of biological sciences.
Article
Biochemistry & Molecular Biology
Mohammad Lotfollahi, Anna Klimovskaia Susmelj, Carlo De Donno, Leon Hetzel, Yuge Ji, Ignacio L. Ibarra, Sanjay R. Srivatsan, Mohsen Naghipourfar, Riza M. Daza, Beth Martin, Jay Shendure, Jose L. McFaline-Figueroa, Pierre Boyeau, F. Alexander Wolf, Nafissa Yakubova, Stephan Guennemann, Cole Trapnell, David Lopez-Paz, Fabian J. Theis
Summary: Recent advances in multiplexed single-cell transcriptomics experiments have enabled high-throughput study of drug and genetic perturbations. However, exhaustive exploration of the combinatorial perturbation space is not feasible experimentally. Therefore, computational methods are needed to predict, interpret, and prioritize perturbations. The compositional perturbation autoencoder (CPA) presented in this study combines linear models' interpretability with deep learning approaches' flexibility to model single-cell response and predict transcriptional perturbation response at the single-cell level for unseen dosages, cell types, time points, and species.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Tai-Ju Hsu, Kunal Nepali, Chi-Hao Tsai, Zuha Imtiyaz, Fan-Li Lin, George Hsiao, Mei-Jung Lai, Yu-Wen Cheng
Summary: AMD, caused by abnormalities in RPE cells, currently lacks diverse treatment options, with anti-VEGF agents being the main therapy despite associated side effects. The study showcases the potential of dual-target modulator G570 in treating wet AMD, indicating promising therapeutic developments in the future.
Article
Multidisciplinary Sciences
Scott A. Scarneo, Aaron P. Smith, Jacob Favret, Robert O'Connell, Joy Pickeral, Kelly W. Yang, Guido Ferrari, David R. Loiselle, Philip F. Hughes, Manjusha M. Kulkarni, Madhusudhana Gargesha, Bryan Scott, Debashish Roy, Barton F. Haynes, Jesse J. Kwiek, Timothy A. J. Haystead
Summary: Hsp90 has been investigated as a therapeutic target in cancer for over two decades. The membrane expressed form of Hsp90 (mHsp90) plays a crucial role in T cell activation and could be a therapeutic target for chronic diseases like rheumatoid arthritis.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Sophia D. Staerz, Erika M. Lisabeth, Evert Njomen, Thomas S. Dexheimer, Richard R. Neubig, Jetze J. Tepe
Summary: The balance between protein degradation and synthesis, proteostasis, is key for proper cellular function. The majority of intracellular protein degradation occurs through the ubiquitin-proteasome system, with pathways targeting unfolded proteins playing an important role. Dysregulation of proteolysis can lead to the accumulation of intrinsically disordered proteins (IDPs), contributing to various diseases. Enhancing the activity of the 20S proteasome using small molecules, such as erlotinib, has shown potential in combating IDP accumulation.
Article
Chemistry, Multidisciplinary
Mengli Zhou, Yushu Ma, Chun-Cheng Chianga, Edwin C. Rock, Kathryn E. Luker, Gary D. Luker, Yu-Chih Chen
Summary: This study presents a high-throughput microfluidic cell migration platform that quantifies individual cellular motility using robotic liquid handling and computer vision. Testing 172 compounds, it found a surprisingly low correlation between migration and growth inhibition. Many compounds were found to inhibit migration of most cells while leaving fast-moving subpopulations unaffected. Additionally, synergistic drug combinations were identified to stop fast-moving cells through single-cell morphological and molecular analysis.
Article
Pharmacology & Pharmacy
Han Sun, Xue-Kai Wang, Jian-Rui Li, Mei Tang, Hu Li, Lei Lei, Hong-Ying Li, Jing Jiang, Jia-Yu Li, Biao Dong, Jian-Dong Jiang, Zong-Gen Peng
Summary: The cell adhesion between leukocytes and endothelial cells plays a crucial role in pathophysiological function, and excessive adhesion caused by etiological agents has been associated with various acute and chronic diseases. Therefore, there is an urgent need for efficient and specific cell adhesion inhibitors to treat these diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Timothy Johnson, Christopher J. Minteer, Daniel Kottmann, Charles R. Dunlop, Sandra Bernaldo de Quiros Fernandez, Larissa S. Carnevalli, Yann Wallez, Alan Lau, Frances M. Richards, Duncan Jodrell
Summary: This study quantitatively described cell cycle-dependent drug sensitivities using a scalable and tolerated method, identifying compounds with G1 and S/G2-associated specificities that matched with a compound's mechanism of action. The findings suggest potential scheduling considerations for drug treatments based on cell cycle specificity, such as using CDK4/6 inhibitors before certain drugs for better efficacy.
Article
Orthopedics
Gen Kuroyanagi, Haruhiko Tokuda, Kazuhiko Fujita, Tetsu Kawabata, Go Sakai, Woo Kim, Tomoyuki Hioki, Junko Tachi, Rie Matsushima-Nishiwaki, Takanobu Otsuka, Hiroki Iida, Osamu Kozawa
Summary: This study demonstrates that HSP90 inhibitors upregulated the TGF-beta-induced HSP27 expression through the SAPK/JNK pathway.
BMC MUSCULOSKELETAL DISORDERS
(2022)
Article
Biochemistry & Molecular Biology
Eleonora Trotta, Paul H. Bessette, Stephanie L. Silveria, Lauren K. Ely, Kevin M. Jude, Duy T. Le, Charles R. Holst, Anthony Coyle, Marc Potempa, Lewis L. Lanier, K. Christopher Garcia, Natasha K. Crellin, Isaac J. Rondon, Jeffrey A. Bluestone
Article
Chemistry, Medicinal
Joerg Bussenius, Charles M. Blazey, Naing Aay, Neel K. Anand, Arlyn Arcalas, TaeGon Baik, Owen J. Bowles, Chris A. Buhr, Simona Costanzo, Jeffrey K. Curtis, Steven C. DeFina, Larisa Dubenko, Timothy S. Heuer, Ping Huang, Christopher Jaeger, Anagha Joshi, Abigail R. Kennedy, Angie I. Kim, Katherine Lara, Jae Lee, Jonathan Li, Julie C. Lougheed, Sunghoon Ma, Shiva Malek, Jean-Claire L. Manalo, Jean-Francois Martini, Garth McGrath, Monique Nicoll, John M. Nuss, Michael Pack, Csaba J. Peto, Tsze H. Tsang, Longcheng Wang, Scott W. Womble, Michael Yakes, Wentao Zhang, Kenneth D. Rice
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2012)
Article
Chemistry, Medicinal
Elena S. Koltun, Amy Lew Tsuhako, David S. Brown, Naing Aay, Arlyn Arcalas, Vicky Chan, Hongwang Du, Stefan Engst, Kim Ferguson, Maurizio Franzini, Adam Galan, Charles R. Holst, Ping Huang, Brian Kane, Moon H. Kim, Jia Li, David Markby, Manisha Mohan, Kevin Noson, Arthur Plonowski, Steven J. Richards, Scott Robertson, Kenneth Shaw, Gordon Stott, Thomas J. Stout, Jenny Young, Peiwen Yu, Cristiana A. Zaharia, Wentao Zhang, Peiwen Zhou, John M. Nuss, Wei Xu, Patrick C. Kearney
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2012)
Article
Chemistry, Medicinal
James W. Leahy, Chris A. Buhr, Henry W. B. Johnson, Byung Gyu Kim, TaeGon Baik, Jonah Cannoy, Timothy P. Forsyth, Joon Won Jeong, Matthew S. Lee, Sunghoon Ma, Kevin Noson, Longcheng Wang, Matthew Williams, John M. Nuss, Eric Brooks, Paul Foster, Leanne Goon, Nathan Heald, Charles Holst, Christopher Jaeger, Scott Lam, Julie Lougheed, Lam Nguyen, Arthur Plonowski, Joanne Song, Thomas Stout, Xiang Wu, Michael F. Yakes, Peiwen Yu, Wentao Zhang, Peter Lamb, Olivia Raeber
JOURNAL OF MEDICINAL CHEMISTRY
(2012)
Article
Multidisciplinary Sciences
Andrew Hinman, Charles R. Holst, Joey C. Latham, Joel J. Bruegger, Gozde Ulas, Kevin P. McCusker, Akiko Amagata, Dana Davis, Kevin G. Hoff, Amanda H. Kahn-Kirby, Virna Kim, Yuko Kosaka, Edgar Lee, Stephanie A. Malone, Janet J. Mei, Steve James Richards, Veronica Rivera, Guy Miller, Jeffrey K. Trimmer, William D. Shrader
Article
Genetics & Heredity
Marie Morimoto, Helen Waller-Evans, Zineb Ammous, Xiaofei Song, Kevin A. Strauss, Davut Pehlivan, Claudia Gonzaga-Jauregui, Erik G. Puffenberger, Charles R. Holst, Ender Karaca, Karlla W. Brigatti, Emily Maguire, Zeynep H. Coban-Akdemir, Akiko Amagata, C. Christopher Lau, Xenia Chepa-Lotrea, Ellen Macnamara, Tulay Tos, Sedat Isikay, Michele Nehrebecky, John D. Overton, Matthew Klein, Thomas C. Markello, Jennifer E. Posey, David R. Adams, Emyr Lloyd-Evans, James R. Lupski, William A. Gahl, May Christine V. Malicdan
AMERICAN JOURNAL OF HUMAN GENETICS
(2018)
Article
Multidisciplinary Sciences
Amanda H. Kahn-Kirby, Akiko Amagata, Celine I. Maeder, Janet J. Mei, Steve Sideris, Yuko Kosaka, Andrew Hinman, Stephanie A. Malone, Joel J. Bruegger, Leslie Wang, Virna Kim, William D. Shrader, Kevin G. Hoff, Joey C. Latham, Euan A. Ashley, Matthew T. Wheeler, Enrico Bertini, Rosalba Carrozzo, Diego Martinelli, Carlo Dionisi-Vici, Kimberly A. Chapman, Gregory M. Enns, William Gahl, Lynne Wolfe, Russell P. Saneto, Simon C. Johnson, Jeffrey K. Trimmer, Matthew B. Klein, Charles R. Holst
Article
Cell Biology
James C. Garbe, Charles R. Holst, Ekaterina Bassett, Thea Tlsty, Martha R. Stampfer
Article
Multidisciplinary Sciences
Charles R. Holst, Hani Bou-Reslan, Bryan B. Gore, Karen Wong, Deanna Grant, Sreedevi Chalasani, Richard A. Carano, Gretchen D. Frantz, Marc Tessier-Lavigne, Brad Bolon, Dorothy M. French, Avi Ashkenazi
Article
Oncology
Jianmin Zhang, Curtis R. Pickering, Charles R. Holst, Mona L. Gauthier, Thea D. Tlsty
Article
Biochemistry & Molecular Biology
KM McDermott, JM Zhang, CR Holst, BK Kozakiewicz, V Singla, TD Tlsty
Article
Oncology
TD Tlsty, YG Crawford, CR Holst, CA Fordyce, JM Zhang, K McDermott, K Kozakiewicz, TD Tlsty
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
(2004)
Article
Oncology
CR Holst, GJ Nuovo, M Esteller, K Chew, SB Baylin, JG Herman, TD Tlsty