Review
Oncology
Boheng Li, Qin Wan, Zhubo Li, Wee-Joo Chng
Summary: Janus kinases (JAKs) are transmembrane receptors that play a role in lymphoid cancer pathogenesis by mediating gene expression through the JAK/STAT pathway. JAK abnormalities can lead to over-activation of the JAK/STAT pathway and the nuclear role of JAK tyrosine kinases. Anti-JAK therapeutics have been developed to effectively target lymphoid cancer cells.
Article
Cell Biology
Bhawana Maurya, Satya Surabhi, Rituparna Das, Pranjali Pandey, Ashim Mukherjee, Mousumi Mutsuddi
Summary: Mahe, an RNA helicase, regulates Notch signaling and neuronal development in Drosophila. The study demonstrates that Mahe can promote apoptosis by modulating the JAK/STAT pathway components. Through transcriptome profiling and RNA immunoprecipitation experiments, the study reveals the regulatory mechanism of Mahe on the JAK/STAT pathway.
CELL DEATH & DISEASE
(2021)
Review
Pharmacology & Pharmacy
Qianqian Yin, Longyun Wang, Haiyang Yu, Daquan Chen, Wenwei Zhu, Changgang Sun
Summary: The JAK-STAT signaling pathway is closely related to cell proliferation, apoptosis, differentiation, and inflammatory response, essential for inhibiting inflammation, initiating innate immunity, and coordinating adaptive immune mechanisms. Various plant polyphenol compounds play a role in suppressing abnormal activation in the JAK-STAT pathway, showing significant effects in anti-inflammatory, antitumor, and cardiovascular disease control.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Yanhua Luo, Tahir Ali, Zizhen Liu, Ruyan Gao, Axiang Li, Canyu Yang, Li Ling, Liufang He, Shupeng Li
Summary: EPO has antidepressant potential by inhibiting inflammatory response and regulating JAK2/STAT5 signaling.
Review
Biochemistry & Molecular Biology
Hyunjung Park, Sangjik Lee, Jaehun Lee, Hyuk Moon, Simon Weonsang Ro
Summary: This review highlights the importance of the JAK/STAT pathway in hepatocellular carcinoma (HCC) and its association with factors such as chronic inflammation and cirrhosis. It also summarizes recent advancements in targeting the JAK/STAT pathway for HCC treatment, emphasizing the potential of this pathway as a promising avenue for therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Antonio Lahera, Laura Vela-Martin, Pablo Fernandez-Navarro, Pilar Llamas, Jose L. Lopez-Lorenzo, Javier Cornago, Javier Santos, Jose Fernandez-Piqueras, Maria Villa-Morales
Summary: This study identified the JAK3(Q988P) mutation in a T-ALL patient, which plays an oncogenic role in leukemogenesis and confers resistance to conventional treatment as well as ruxolitinib. These findings highlight the importance of evaluating this mutation for guiding personalized therapeutic strategies.
MOLECULAR CARCINOGENESIS
(2023)
Article
Cardiac & Cardiovascular Systems
Nannan Hao, Zihao Zhou, Feifei Zhang, Yong Li, Rui Hu, Junjie Zou, Rui Zheng, Lei Wang, Lingxiao Xu, Wenfeng Tan, Chunjian Li, Fang Wang
Summary: Vascular calcification (VC), characterized by the osteogenic transdifferentiation of vascular smooth muscle cells, is associated with enhanced cardiovascular morbidity and mortality. Inflammation plays a key role in VC initiation and progression. IL-29, a member of type III interferon, is implicated in the pathogenesis of autoimmune diseases. This study evaluated the role of IL-29 in VC and its underlying inflammatory mechanisms.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Review
Oncology
Alexander Ou, Martina Ott, Dexing Fang, Amy B. Heimberger
Summary: Glioblastoma is a highly refractory and deadly human malignancy, with the dysregulated JAK/STAT signaling pathway playing a key role in tumorigenesis and resistance to therapy, influencing functions such as proliferation, anti-apoptosis, angiogenesis, stem cell maintenance, and immune suppression. Current understanding of JAK/STAT signaling in glioblastoma highlights the need for targeted inhibition and future research directions in the field.
Review
Pharmacology & Pharmacy
Qiuyu Pang, Lu You, Xiangmin Meng, Yumeng Li, Tian Deng, Deyong Li, Bingmei Zhu
Summary: The JAK/STAT signaling pathway plays a crucial role in cell growth, differentiation, immune response, and hematopoietic system development. It has been found to have regulatory functions in various cardiovascular diseases, such as myocardial ischemia-reperfusion injury, acute myocardial infarction, hypertension, myocarditis, heart failure, angiogenesis, and fibrosis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Yuqian Chang, Pan Kang, Tingting Cui, Weinan Guo, Weigang Zhang, Pengran Du, Xiuli Yi, Sen Guo, Tianwen Gao, Chunying Li, Shuli Li
Summary: T-96, extracted from Tripterygium wilfordii Hook F, has been found to have anti-inflammatory and immunosuppressive properties. It can effectively inhibit the activation and infiltration of CD8(+) T cells in the skin, making it a potential therapeutic option for vitiligo.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Medicine, General & Internal
Malgorzata Galecka, Janusz Szemraj, Kuan-Pin Su, Angelos Halaris, Michael Maes, Aleksandra Skiba, Piotr Galecki, Katarzyna Blizniewska-Kowalska
Summary: This study found that there is increased expression of JAK3 and decreased expression of STAT1 in depressed patients.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Sara La Manna, Ilaria De Benedictis, Daniela Marasco
Summary: The JAK-STAT pathway is a vital signaling cascade involved in regulating various cellular activities. It plays a crucial role in immune responses, neuroinflammatory diseases, and tumor cell recognition. Targeting JAK-STAT, particularly through the use of natural inhibitors such as SOCS proteins, has potential in immunotherapeutic approaches to cancer and immune deficiency disorders.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Diana Rodrigues, Yoan Renaud, K. VijayRaghavan, Lucas Waltzer, Maneesha S. Inamdar
Summary: This study reveals the heterogeneity of posterior progenitors (PP) in the Drosophila larval lymph gland and identifies molecular-genetic tools for studying this cell population. Functional analysis shows that PP resist differentiation upon immune challenge, promoting survival in a JAK-STAT-dependent manner, contrasting with the response of anterior lobe progenitors (AP).
Article
Biochemistry & Molecular Biology
Lena Jakob, Tony Andreas Mueller, Michael Rassner, Helen Kleinfelder, Pia Veratti, Jan Mitschke, Cornelius Miething, Robert A. J. Oostendorp, Dietmar Pfeifer, Miguel Waterhouse, Justus Duyster
Summary: The IL-6 family cytokine Oncostatin M (OSM) has various effects on cell development, growth, hematopoiesis, inflammation, and cancer. It can have both proliferative and antiproliferative effects depending on the target cell, with mechanisms involving OSM receptors and signaling pathways. Studies in murine cells show that OSM affects proliferation in stromal and fibroblast cell lines by activating JAK-STAT, PI3K-AKT, and MAPK-ERK pathways through OSMR, offering new insights into proliferation regulation by mOSM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Allergy
Yiming Luo, Madison Alexander, Massimo Gadina, John J. O'Shea, Francoise Meylan, Daniella M. Schwartz
Summary: The JAK-STAT pathway is recognized as a central mediator of human physiological processes, with genomic sequencing leading to the discovery of clinical syndromes caused by mutations in JAK and STAT genes. Additionally, the therapeutic use of JAK inhibitors has expanded to include various diseases, with clinical studies providing mechanistic insights and improving patient care.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Swann Floc'hlay, Emily S. Wong, Bingqing Zhao, Rebecca R. Viales, Morgane Thomas-Chollier, Denis Thieffry, David A. Garfield, Eileen E. M. Furlong
Summary: Genetic variation (allelic imbalance) more frequently impacts gene expression, especially metabolic and environmental response genes. Allelic imbalance in cis-regulatory elements is common and highly heritable, but generally does not propagate to gene expression. Genetic variation affects RNA levels through mechanisms involving H3K4me3 or chromatin accessibility and H3K27ac.
Review
Cell Biology
Gabriel R. Cavalheiro, Tim Pollex, Eileen E. M. Furlong
Summary: The past decade has witnessed significant advancements in understanding the three-dimensional properties of the genome, particularly in terms of chromatin structures and their impact on gene expression. However, there is still much to learn about the underlying mechanisms and functional roles of genome topology. Recent studies utilizing genetic manipulations have provided new insights into the relationship between genome topology and gene expression, with a focus on enhancer function.
CURRENT OPINION IN GENETICS & DEVELOPMENT
(2021)
Article
Cell Biology
Anna C. Koegler, Yacine Kherdjemil, Katharina Bender, Adam Rabinowitz, Raquel Marco-Ferreres, Eileen E. M. Furlong
Summary: Many developmental regulators have complex and context-specific roles in different tissues and stages, making the dissection of their function extremely challenging. The improved light-inducible nuclear export system (iLEXY) enables rapid, efficient, and reversible nuclear protein depletion in embryos, and is generalizable to proteins of diverse sizes and functions, highlighting its power in dissecting the function of pleiotropic factors during embryogenesis with unprecedented temporal precision.
DEVELOPMENTAL CELL
(2021)
Article
Cell Biology
Stefano Secchia, Mattia Forneris, Tobias Heinen, Oliver Stegle, Eileen E. M. Furlong
Summary: This study combines single-cell regulatory genomics with loss-of-function mutants to systematically evaluate the functional input of transcription factors (TFs) and uncover cellular and molecular phenotypes. By performing experiments at different time points during Drosophila embryo development, the researchers reconstruct the developmental trajectories and identify the TFs and enhancers involved in major muscle types. They also develop a single-nucleus genotyping strategy to assess mutant phenotypes and discover new ones while revealing regulatory input and mode of action.
DEVELOPMENTAL CELL
(2022)
Article
Cell Biology
Charalampos Chrysovalantis Galouzis, Eileen E. M. Furlong
Summary: Enhancers are cis-regulatory elements that can activate transcription remotely to regulate a specific pattern of gene expression. Mechanisms of enhancer-promoter communication, including the role of cohesin and the Mediator complex, as well as the genetic dissection and genome-wide approaches, highlight key components such as core promoter sequence and genomic context.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Article
Biology
Jean-Philippe Mocho, Florian Lang, Guillaume Valentin, Sebastien Bedu, Robin McKimm, Juan Ramos, Yolanda Saavedra Torres, Sarah E. Wheatley, Joseph Higgins, Mollie E. Millington, Pia Rengtved Lundegaard, Ruben Chamorro Valverde, Vlasta Jencic, Kristine von Krogh
Summary: The study evaluated the euthanasia effectiveness of different methods on zebrafish larvae in laboratories from various countries, with overdose of clove oil, lidocaine with ethanol, and electrical stunning being the most effective. Lidocaine was found to be the most suitable euthanasia treatment for older larvae, and further assessment is needed for the electrical stunning method.
Article
Multidisciplinary Sciences
Diego Calderon, Ronnie Blecher-Gonen, Xingfan Huang, Stefano Secchia, James Kentro, Riza M. Daza, Beth Martin, Alessandro Dulja, Christoph Schaub, Cole Trapnell, Erica Larschan, Kate M. O'Connor-Giles, Eileen E. M. Furlong, Jay Shendure
Article
Multidisciplinary Sciences
Kim Theilgaard-Monch, Sachin Pundhir, Kristian Reckzeh, Jinyu Su, Marta Tapia, Benjamin Furtwangler, Johan Jendholm, Janus Schou Jakobsen, Marie Sigurd Hasemann, Kasper Jermiin Knudsen, Jack Bernard Cowland, Anna Fossum, Erwin Schoof, Mikkel Bruhn Schuster, Bo T. Porse
Summary: This study reveals the regulatory mechanism of tissue-specific transcription factors in cell differentiation, which first launch an enhancer-primed differentiation program, then promote cell cycle exit by repressing MYC target gene expression and E2F-mediated gene expression, and by up-regulating Cdk1/2/4 inhibitors. Following cell cycle exit, the primed differentiation program is activated for terminal differentiation.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Blanca Pijuan-Sala, Eileen E. M. Furlong
Article
Biology
Katrin Moller, Max Brambach, Ambra Villani, Elisa Gallo, Darren Gilmour, Francesca Peri
Summary: The migration of the centrosome in microglia is a crucial step in the engulfment of apoptotic cells. Additionally, microglia demonstrate plasticity in their phagocytic ability, as they can switch between different modes of engulfment under certain conditions.
Article
Multidisciplinary Sciences
Gabriel R. Cavalheiro, Charles Girardot, Rebecca R. Viales, Tim Pollex, T. B. Ngoc Cao, Perrine Lacour, Songjie Feng, Adam Rabinowitz, Eileen E. M. Furlong
Summary: During early Drosophila embryogenesis, most TAD boundaries are established by a combination of CTCF, BEAF-32, and CP190, although a subset of boundaries show higher dependence on specific insulators. Weakened boundaries result in aberrant gene expression due to unconstrained enhancer activity.
Article
Multidisciplinary Sciences
Anne Meldgaard Hansen, Ying Ge, Mikkel Bruhn Schuster, Sachin Pundhir, Janus Schou Jakobsen, Adrija Kalvisa, Marta Cecylia Tapia, Sandra Gordon, Francesca Ambri, Frederik Otzen Bagger, Deo Pandey, Kristian Helin, Bo Torben Porse
Summary: The study reveals that H3K9me2 is crucial for the proliferation of AML and its loss leads to activation of the interferon pathway. Mechanistically, destabilization of a complex involving SUV39H1, G9A, and GLP is responsible for this activation.
Article
Biotechnology & Applied Microbiology
Tobias Heinen, Stefano Secchia, James P. Reddington, Bingqing Zhao, Eileen E. M. Furlong, Oliver Stegle
Summary: In this paper, the authors developed a computational framework called scDALI to characterize the genetic effects specific to certain cell states. Application of scDALI to single-cell sequencing data from fruit fly embryos and human iPSCs revealed heterogeneous genetic effects in specific lineages, developmental stages, or cell types.
Meeting Abstract
Oncology
Janus S. Jakobsen, Matteo Riva, Maria C. Melander, Randi W. Hansen, Klaus Kofoed, Mikkel W. Pedersen, Jutta Deckert, Lene Hansen, Niels Jorgen Skartved, Johan Lantto, Camilla Frohlich, Michael Monrad Grandal
Review
Multidisciplinary Sciences
Liesbeth Minnoye, Georgi K. Marinov, Thomas Krausgruber, Lixia Pan, Alexandre P. Marand, Stefano Secchia, William J. Greenleaf, Eileen E. M. Furlong, Keji Zhao, Robert J. Schmitz, Christoph Bock, Stein Aerts
Summary: This article discusses the characteristics and biochemical methods of chromatin accessibility, emphasizing its importance in identifying candidate regulatory genomic regions. It also mentions the use of bioinformatics tools for data interpretation and discovery of key regulators, as well as the maintenance of data quality and reproducibility. Lastly, it points out that while chromatin accessibility profiling is valuable, it needs to be complemented with orthogonal assays to explain the complex gene regulation process.
NATURE REVIEWS METHODS PRIMERS
(2021)
