Article
Cell Biology
Eunice Cho, Hua Jane Lou, Leena Kuruvilla, David A. Calderwood, Benjamin E. Turk
Summary: This study identifies PPP6C as a crucial phosphatase for MEK in the ERK pathway, which is frequently mutated or downregulated in melanoma. Loss of PPP6C leads to hyperphosphorylation of MEK, enhancing signaling through the pathway and reducing sensitivity to MEK inhibitors. Its recurrent mutations in melanoma cause MEK hyperphosphorylation, suggesting their role in promoting the disease by activating the core oncogenic pathway.
Article
Multidisciplinary Sciences
Sandro Sousa, Vincenzo Nicosia
Summary: This study proposes a non-parametric measurement method to quantify socioeconomic segregation in urban areas through diffusion. The method allows for effective comparison of segregation levels in different urban areas and shows a strong association with socioeconomic deprivation.
NATURE COMMUNICATIONS
(2022)
Review
Ecology
Felipe Franco-Gaviria, Monica Amador-Jimenez, Naomi Millner, Charlotte Durden, Dunia H. Urrego
Summary: This study provides a theoretical and conceptual framework to quantify the resilience of socio-ecological systems (SES) in a long-term context. The approach combines elements from interdisciplinarity and network perspectives, using dynamic Bayesian networks (DBN) to establish links between social and ecological variables and resilience attributes. The proposed DBN is tested in Monquentiva, Colombia, and the results show that social change and increased ecological diversity foster SES resilience. The ability to predict SES response over time and under complex interactions highlights the utility of DBNs for decision support and environmental management.
FRONTIERS IN FORESTS AND GLOBAL CHANGE
(2022)
Article
Biology
Gary K. L. Chan, Samantha Maisel, Yeonjoo C. Hwang, Bryan C. Pascual, Rebecca R. B. Wolber, Phuong Vu, Krushna C. Patra, Mehdi Bouhaddou, Heidi L. Kenerson, Huat C. Lim, Donald Long, Raymond S. Yeung, Praveen Sethupathy, Danielle L. Swaney, Nevan J. Krogan, Rigney E. Turnham, Kimberly J. Riehle, John D. Scott, Nabeel Bardeesy, John D. Gordan
Summary: Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. The downstream oncogenic signaling mechanisms of PKA activation in human cancer were explored using phosphoproteomics and kinase activity profiling. Two signaling networks, RAS/MAPK components and an AURKA/GSK3 sub-network, were identified, both affecting MYC oncoproteins. Primary mechanism of PKA effects on MYC was found to be translation, which could be blocked with the eIF4A inhibitor zotatifin, suggesting a potential treatment strategy for PKA-driven cancers.
Review
Biochemistry & Molecular Biology
Ammad Ahmad Farooqi, Rukset Attar, Baojun Xu
Summary: Cancer is a life-threatening disease that has been extensively studied in the past three decades. Thymoquinone, a natural product, has shown promising potential in cancer chemoprevention through its multifunctionality. Further research is needed to transition thymoquinone from preclinical studies to clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Engineering, Biomedical
Payam E. Farahani, Ellen H. Reed, Evan J. Underhill, Kazuhiro Aoki, Jared E. Toettcher
Summary: Cells receive information from their environment and use optogenetic tools to study how they decode signals and produce appropriate responses. Optogenetics helps researchers manipulate protein interactions and activities with precision, leading to a better understanding and engineering of biology.
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING, VOL 23, 2021
(2021)
Review
Oncology
Antonia Schubert, Michael Boutros
Summary: Extracellular vesicles (EVs) have emerged as potential diagnostic and prognostic markers for cancer therapy, yet much remains unknown about their exact mechanisms of signaling specificity and cargo transfer. Several signaling cascades utilize EVs for signaling in tumor-stroma interaction, including key pathways such as Wnt and TGF-beta, which are tightly associated with tumor progression and metastasis. Multiple mechanisms of how EVs interplay with signaling cascades to mediate complex processes have been described, shedding light on the potential therapeutic applications and gaps in knowledge.
MOLECULAR ONCOLOGY
(2021)
Article
Cell Biology
GuoYan Wang, SenLin Qin, Lei Chen, HuiJun Geng, YiNing Zheng, Chao Xia, JunHu Yao, Lu Deng
Summary: This study found that sodium butyrate (NaB) enhances RSL3- and erastin-induced cell ferroptosis by downregulating the expression of SLC7A11 and GPX4, leading to lipid ROS production. The FFAR2-AKT-NRF2 and FFAR2-mTORC1 axes mediate the downregulation of SLC7A11 and GPX4 by NaB in a cAMP-PKA-dependent manner. Functionally, NaB inhibits tumor growth and this effect can be reversed by the mTORC1 activator MHY1485 and the ferroptosis inhibitor Ferr-1. Overall, NaB treatment can induce mTOR-dependent ferroptosis and suppress tumor growth, suggesting its potential clinical applications for colorectal cancer treatment.
CELL DEATH & DISEASE
(2023)
Article
Gastroenterology & Hepatology
Lu Tian, Luqing Zhao, Karen Man-Fong Sze, Charles Shing Kam, Vanessa Sheung-In Ming, Xia Wang, Vanilla Xin Zhang, Daniel Wai-Hung Ho, Tan-To Cheung, Lo-Kong Chan, Irene Oi-Lin Ng
Summary: RalA is significantly up-regulated in HCC patients and associated with aggressive tumor behavior and poor prognosis. Its up-regulation is driven by copy number gain, while RalGAPA2 knockdown increases RalA activity. Tumors with down-regulated RalGAPA2 and up-regulated RalA display more aggressive behavior and poorer survival, with Ral inhibition showing potential as a therapeutic approach.
Article
Biochemistry & Molecular Biology
Marine Beck, Mathilde Baranger, Ahlam Moufok-Sadoun, Emilie Bersuder, Isabelle Hinkel, Georg Mellitzer, Elisabeth Martin, Laetitia Marisa, Isabelle Duluc, Aurelien de Reynies, Christian Gaiddon, Jean-Noel Freund, Isabelle Gross
Summary: This study focused on the atypical cadherin MUCDHL, which is down-regulated in colorectal tumors, especially in tumors with worse prognosis. Loss of MUCDHL enhanced tumor incidence and burden in intestinal tumor-prone mice, and targeted key oncogenic signaling pathways through its extracellular domain. The study illustrates how the loss of a gene critical for the morphological and functional features of mature cells contributes to tumorigenesis by dysregulating oncogenic pathways.
Review
Microbiology
Madeline R. Barron, Vincent B. Young
Summary: The relationship between the gut environment and bacterial colonization is of great significance. The complex interactions between multiple factors in the gut environment make it difficult to uncover the characteristics of the system using reductionist methods. The systems biology approach provides a more comprehensive perspective. This article explores the relationship between the gut environment and bacterial colonization from the perspective of systems biology, and provides guidance for future research.
Article
Oncology
Jiji T. Kurup, Seongho Kim, Benjamin L. Kidder
Summary: Using a network biology framework, we identified cancer type-specific gene regulatory networks for 17 types of cancer, and elucidated core transcription factors and regulatory networks for multiple cancer types. By comparing normal tissues and cells to cancer type-specific networks, we found that the expression of key network-influencing factors can serve as a prognostic indicator for cancer patients.
Article
Medicine, Research & Experimental
Argelia Calvillo-Robledo, Rodolfo Daniel Cervantes-Villagrana, Paula Morales, Bruno A. Marichal-Cancino
Summary: GPR55 is an orphan receptor that has been found to play a crucial role in various pathophysiological processes. This receptor can be modulated by cannabinoids and is proposed to be a part of the endocannabinoid system. The LPI/GPR55 axis is involved in cell survival and tumor progression, and has potential as a biomarker for cancer diagnosis.
Article
Biochemistry & Molecular Biology
Chao Wang, Jonathan Leavenworth, Chao Zhang, Zhichao Liu, Katherine Y. Yuan, Yicun Wang, Guangxin Zhang, Shuaibin Wang, Xuelian Cui, Yue Zhang, Sejong Bae, Jiangbing Zhou, Lizhong Wang, Runhua Liu
Summary: In prostate cancer, high expression of eIF4A1 is regulated by DNA methylation and it plays an oncogenic role through the BRD2 signaling pathway.
Article
Medicine, Research & Experimental
Won Gun Choi, Wonsuk Choi, Tae Jung Oh, Hye-Na Cha, Inseon Hwang, Yun Kyung Lee, Seung Yeon Lee, Hyemi Shin, Ajin Lim, Dongryeol Ryu, Jae Myoung Suh, So-Young Park, Sung Hee Choi, Hail Kim
Summary: Inhibition of serotonin signaling in adipose tissues can improve insulin resistance by reducing lipolysis.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Joshua A. Jadwin, Timothy G. Curran, Adam T. Lafontaine, Forest M. White, Bruce J. Mayer
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Oncology
Hui Liu, Charles J. Murphy, Florian A. Karreth, Kristina B. Emdal, Kangkang Yang, Forest M. White, Olivier Elemento, Alex Toker, Gerburg M. Wulf, Lewis C. Cantley
Article
Chemistry, Physical
Efrat Flashner-Abramson, Jonathan Abramson, Forest M. White, Nataly Kravchenko-Balasha
Article
Biochemistry & Molecular Biology
Ruedi Aebersold, Jeffrey N. Agar, I. Jonathan Amster, Mark S. Baker, Carolyn R. Bertozzi, Emily S. Boja, Catherine E. Costello, Benjamin F. Cravatt, Catherine Fenselau, Benjamin A. Garcia, Ying Ge, Jeremy Gunawardena, Ronald C. Hendrickson, Paul J. Hergenrother, Christian G. Huber, Alexander R. Ivanov, Ole N. Jensen, Michael C. Jewett, Neil L. Kelleher, Laura L. Kiessling, Nevan J. Krogan, Martin R. Larsen, Joseph A. Loo, Rachel R. Ogorzalek Loo, Emma Lundberg, Michael J. MacCoss, Parag Mallick, Vamsi K. Mootha, Milan Mrksich, Tom W. Muir, Steven M. Patrie, James J. Pesavento, Sharon J. Pitteri, Henry Rodriguez, Alan Saghatelian, Wendy Sandoval, Hartmut Schluter, Salvatore Sechi, Sarah A. Slavoff, Lloyd M. Smith, Michael P. Snyder, Paul M. Thomas, Mathias Uhlen, Jennifer E. Van Eyk, Marc Vidal, David R. Walt, Forest M. White, Evan R. Williams, Therese Wohlschlager, Vicki H. Wysocki, Nathan A. Yates, Nicolas L. Young, Bing Zhang
NATURE CHEMICAL BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Martin Schwill, Rastislav Tamaskovic, Aaron S. Gajadhar, Florian Kast, Forest M. White, Andreas Pluckthun
Article
Biochemistry & Molecular Biology
Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White
MOLECULAR SYSTEMS BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Lauren E. Stopfer, Joshua M. Mesfin, Brian A. Joughin, Douglas A. Lauffenburger, Forest M. White
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Ritu Raman, Erin B. Rousseau, Michael Wade, Allison Tong, Max J. Cotler, Jenevieve Kuang, Alejandro Aponte Lugo, Elizabeth Zhang, Ann M. Graybiel, Forest M. White, Robert Langer, Michael J. Cima
Article
Multidisciplinary Sciences
Walid M. Abdelmoula, Begona Gimenez-Cassina Lopez, Elizabeth C. Randall, Tina Kapur, Jann N. Sarkaria, Forest M. White, Jeffrey N. Agar, William M. Wells, Nathalie Y. R. Agar
Summary: This study demonstrates the application of artificial intelligence in mining Mass Spectrometry Imaging (MSI) data to reveal biologically relevant metabolomic and proteomic information acquired from different mass spectrometry platforms. By utilizing a fully connected variational autoencoder, the researchers developed the msiPL method to learn and visualize the underlying non-linear spectral manifold in MSI data, uncovering biologically relevant clusters of tissue anatomy and tumor heterogeneity in various tissue types.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Ishwar N. Kohale, Jia Yu, Yongxian Zhuang, Xiaoyang Fan, Raven J. Reddy, Jason Sinnwell, Krishna R. Kalari, Judy C. Boughey, Jodi M. Carter, Matthew P. Goetz, Liewei Wang, Forest M. White
Summary: Breast cancer is the leading cause of cancer-related deaths in women globally, with triple negative breast cancer (TNBC) known for being highly aggressive and resistant to chemotherapy. In this study, the researchers identified Src family kinases (SFKs) as potential drug targets for chemotherapy-resistant TNBC. However, the prevalence of SFK-driven tumors was found to be low in human tumor tissue specimens. These findings highlight the importance of characterizing phosphotyrosine signaling profiles for patient stratification and therapeutic options.
Article
Multidisciplinary Sciences
Lauren E. Stopfer, Nicholas J. Rettko, Owen Leddy, Joshua M. Mesfin, Eric Brown, Shannon Winski, Bryan Bryson, James A. Wells, Forest M. White
Summary: Combining multiple therapeutic strategies may improve survival benefits for NRAS/BRAF mutant melanoma patients. This study utilized immunopeptidomics to measure the impact of MEK inhibition on anti-tumor immunity and identified enhanced expression of specific tumor antigens following therapy. Targeting these upregulated tumor antigens can enhance cell killing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Owen Leddy, Forest M. White, Bryan D. Bryson
Article
Biology
Jacqueline S. Gerritsen, Joseph S. Faraguna, Rudy Bonavia, Frank B. Furnari, Forest M. White
Summary: This study investigated the relationship between specific EGFR phosphorylation sites and the signaling network as well as cell response. The results showed that the EGFR network remains resilient even with multiple Y-to-F mutations in the C-terminal tail. Additionally, the study revealed previously unidentified network nodes associated with EGFR signaling. The data-driven model highlighted the signaling network nodes associated with distinct EGF-driven cell responses.
LIFE SCIENCE ALLIANCE
(2023)
Article
Cell Biology
Nader Morshed, Meelim J. Lee, Felicia H. Rodriguez, Douglas A. Lauffenburger, Diego Mastroeni, Forest M. White
Summary: The study analyzed the proteome and phosphoproteome of brain tissue from Alzheimer's disease patients, uncovering correlations between neuronal synaptic protein abundances, microglial reactivity markers, and phosphorylation sites on kinases targeting tau. This provides insight into pathology-associated phosphorylation signaling events in Alzheimer's disease.
Article
Biology
Brian C. Del Rosario, Andrea J. Kriz, Amanda M. Del Rosario, Anthony Anselmo, Christopher J. Frye, Forest M. White, Ruslan Sadreyev, Jeannie T. Lee