Article
Cell Biology
Kathleen Zohorsky, Shigang Lin, Kibret Mequanint
Summary: The study demonstrated that utilizing bead-bound Jagged1 was effective in activating Notch3 and promoting SMC differentiation/maturation, while magnetic pulling forces did not activate Notch3 but instead provided necessary clustering or traction forces for Notch activation. The findings suggest that manipulation of Jagged1 presentation strategy can improve biomaterial-driven control of SMC behavior.
Article
Developmental Biology
Oscar Cazares, Sharmila Chatterjee, Pinky Lee, Catherine Strietzel, J. W. Bubolz, Gwyndolen Harburg, Jon Howard, Sol Katzman, Jeremy Sanford, Lindsay Hinck
Summary: The study identifies a regulatory pathway in the mammary gland that controls alveolar progenitor differentiation and lactation by governing Notch activation, where ROBO1 plays a crucial role.
Review
Biotechnology & Applied Microbiology
Sundus Kaimari, Archana Kamalakar, Steven L. Goudy
Summary: JAG1 is an important ligand for the NOTCH signaling pathway, necessary for differentiation of stem cells and cranial neural crest cells. However, delivery of soluble JAG1 inhibits NOTCH signaling, so alternative immobilization approaches are being explored. This review discusses the role of JAG1 in disease, its potential as a therapeutic agent, and current delivery methods.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Immunology
Yang Chen, Hua Huang, Wen Zhong, Lan Li, Yanrong Lu, Hai-bo Si
Summary: This study aimed to investigate the role and potential mechanism of microRNA-140-5p (miR-140-5p) in cartilage progenitor/stem cells (CPCs) fate changes and regulatory mechanisms in osteoarthritis (OA) pathogenesis. The findings revealed that fate changes in OA CPCs were associated with downregulation of miR-140-5p and upregulation of Jagged1 and Notch signals. Furthermore, miR-140-5p was found to protect CPCs by inhibiting Jagged1/Notch signaling, providing attractive targets for OA therapeutics.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Simona Hankeova, Noemi Van Hul, Jakub Laznovsky, Elisabeth Verboven, Katrin Mangold, Naomi Hensens, Csaba Adori, Elvira Verhoef, Tomas Zikmund, Feven Dawit, Michaela Kavkova, Jakub Salplachta, Marika Sjoqvist, Bengt R. Johansson, Mohamed G. Hassan, Linda Fredriksson, Karsten Baumgartel, Vitezslav Bryja, Urban Lendahl, Andrew Jheon, Florian Alten, Kristina Tear Fahnehjelm, Bjorn Fischler, Jozef Kaiser, Emma R. Andersson
Summary: This study found significant sex differences in spontaneous bleeding events reported by ALGS patients, with more girls than boys experiencing intracranial hemorrhage. Jag1(Ndr/Ndr) mice displayed various vascular defects, and retinography proved to be a non-invasive method to analyze vascular changes in patients.
EMBO MOLECULAR MEDICINE
(2022)
Article
Orthopedics
Jianping Zhang, Na Li, Siyu Lu, Yanling Chen, Lequn Shan, Xingcheng Zhao, Yongqing Xu
Summary: The high expression of Jagged1 is closely related to the metastasis and recurrence of osteosarcoma in 68 clinical specimens. Expression of Jagged1 was significantly higher in F5M2 cells with high metastasis compared to F4 cells with low metastasis. Knockdown of Jagged1 led to reduced proliferation, migration, and invasion abilities in osteosarcoma cells.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2021)
Review
Neurosciences
Sean J. Miller, Cameron E. Campbell, Helen A. Jimenez-Corea, Guan-Hui Wu, Robert Logan
Summary: Parkinson's disease is a common neurodegenerative disease without a cure. While research often focuses on neurons, this review highlights the important role of neuroglia in the disease. Factors such as oxidative stress and neuroinflammation are discussed, along with the potential therapeutic avenue of senolytics for PD.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Orthopedics
Guangxi Wang, Jinglong Yan, Hao Zhang, Patrick Massey, J. Steven Alexander, Christopher G. Kevil, Shane Barton, Yufeng Dong
Summary: This study demonstrates that Notch activation in vivo can be induced by injecting Jagged1 peptide, leading to enhanced bone callus formation during allograft healing in a femur bone defect mouse model. The translational potential of this therapeutic strategy includes immediate application in chronic long bone defect repair and potential application in enhancing repair of other tissues and organs.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2021)
Article
Pharmacology & Pharmacy
M. Carmen Ruiz-Cantero, Rafael Gonzalez-Cano, Miguel A. Tejada, Miriam Santos-Caballero, Gloria Perazzoli, Francisco R. Nieto, Enrique J. Cobos
Summary: This article discusses the modulatory effects of sigma-1 receptors on communication between the immune and nervous systems during inflammation, as well as their influence on peripheral and central neuroinflammation. Experimental models show that sigma-1 receptor inhibition can prevent neuroinflammation and enhance immune-driven opioid analgesia, potentially making sigma-1 antagonists a new class of analgesics for various painful disorders.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Oncology
Chaofeng Li, Zhengju Chen, Jinli Gao, Tao Tang, Lei Zhou, Guochao Zhang, Dongdong Zhang, Chao Shen, Lei Guo, Tao Fu
Summary: This study identified the potential role of lncRNA MIR4435-2HG in gastric cancer (GC) tumorigenesis. Inhibition of MIR4435-2HG reduced the viability and migration ability of GC cells. Moreover, delivery of MIR4435-2HG shRNA via exosomes reversed macrophage M2 polarization and inhibited GC tumor growth.
FRONTIERS IN ONCOLOGY
(2022)
Article
Microbiology
Junjie Wen, Chuxi Chen, Meiqun Luo, Xiaocong Liu, Jiading Guo, Tingting Wei, Xinyi Gu, Sinan Gu, Yunshan Ning, Yan Li
Summary: The study highlights the significant role of the Notch signaling pathway in macrophages's response against Helicobacter pylori, with Jagged1 identified as a promoting molecule for bactericidal activities. This finding suggests Jagged1 could be a novel therapeutic target for controlling H. pylori infection.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Medicine, Research & Experimental
Letizia Porcelli, Annalisa Mazzotta, Marianna Garofoli, Roberta Di Fonte, Gabriella Guida, Michele Guida, Stefania Tommasi, Amalia Azzariti
Summary: The crosstalk between Notch and MAPK pathway is involved in MEK inhibitor resistance in metastatic melanoma and promotes migration in uveal melanoma cells. The combination of MEK and Notch inhibitors shows synergistic effects in some cells and antagonistic effects in others. In uveal melanoma cells, the combination therapy can block cell migration towards liver cancer cells and induce cells into a senescent-like state.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Gastroenterology & Hepatology
Nima Niknejad, Duncan Fox, Jennifer L. Burwinkel, Neda Zarrin-Khameh, Soomin Cho, Armand Soriano, Ashley E. Cast, Mario F. Lopez, Kari A. Huppert, Frank Rigo, Stacey S. Huppert, Paymaan Jafar-Nejad, Hamed Jafar-Nejad
Summary: This study investigates a new therapeutic strategy for treating liver disease in patients with Alagille syndrome by reducing the levels of Poglut1. The results show that this approach can improve liver phenotypes in mouse models and may have potential for other diseases associated with bile duct paucity.
Article
Cell Biology
Eun-Jun Kim, Jung Yun Kim, Sung-Ok Kim, Nayoung Hong, Sang-Hun Choi, Min Gi Park, Junseok Jang, Seok Won Ham, Sunyoung Seo, Seon Yong Lee, Kanghun Lee, Hyeon Ju Jeong, Sung Jin Kim, Sohee Jeong, Kyungim Min, Sung-Chan Kim, Xiong Jin, Se Hoon Kim, Sung-Hak Kim, Hyunggee Kim
Summary: JAG1 intracellular domain (JICD1) induces cancer stem cell properties and tumorigenicity by forming a transcriptional complex with DDX17, SMAD3, and TGIF2 to increase SOX2 expression.
Article
Neurosciences
Frederick Wasinski, Mariana R. Tavares, Daniela O. Gusmao, Edward O. List, John J. Kopchick, Guilherme A. Alves, Renata Frazao, Jose Donato Jr
Summary: The present study aimed to investigate the effects of central growth hormone (GH) action on glial function in male mice. It was found that the expression of several neuroglial markers in the hypothalamus was decreased in dwarf GH- and insulin-like growth factor-1 (IGF-1)-deficient mice, while transgenic overexpression of GH led to increased expression of these markers. Moreover, hepatocyte-specific GH receptor knockout mice showed increased expression of glial markers, independent of IGF-1 secretion, while brain-specific GH receptor knockout mice showed reduced expression of these markers. These findings suggest that GHR signaling directly modulates the mRNA levels of neuroglial markers associated with inflammation.
NEUROSCIENCE LETTERS
(2023)
Article
Clinical Neurology
Jasia Mahdi, Manu S. Goyal, Jennifer Griffith, Stephanie M. Morris, David H. Gutmann
Article
Oncology
Nicole M. Brossier, Sharanya Thondapu, Olivia M. Cobb, Sonika Dahiya, David H. Gutmann
Summary: The study identified three factors that may contribute to the temporal patterning and penetrance of NF1 optic glioma: different populations of TVZ NPCs, decreased NPC proliferation after birth, and differential impact of germline Nf1 mutations on TVZ NPC expansion during embryogenesis.
Article
Medicine, Research & Experimental
Juan Mo, Corina Anastasaki, Zhiguo Chen, Tracey Shipman, Jason Papke, Kevin Yin, David H. Gutmann, Lu Q. Le
Summary: NF1 gene mutation causes abnormal differentiation of Schwann cells, leading to expansion of progenitor cells and promoting neurofibroma development. This study established humanized neurofibroma explant and genetically engineered nodular cutaneous neurofibroma mouse models for future therapeutic target discovery and evaluation.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Nicole J. Ullrich, Sanjay P. Prabhu, Roger J. Packer, Stewart Goldman, Nathan J. Robison, Jeffrey C. Allen, David H. Viskochil, David H. Gutmann, John P. Perentesis, Bruce R. Korf, Michael J. Fisher, Mark W. Kieran
Summary: In children with neurofibromatosis type 1-associated optic pathway gliomas (NF1-OPGs), visual acuity tends to stabilize or improve after treatment with everolimus, although there may be discrepancies between visual and radiologic outcomes.
PEDIATRIC BLOOD & CANCER
(2021)
Article
Oncology
Till Milde, Fausto J. Rodriguez, Jill S. Barnholtz-Sloan, Nirav Patil, Charles G. Eberhart, David H. Gutmann
Summary: pLGGs are the most common brain tumor in children, but our understanding of their molecular and cellular pathogenesis remains incomplete. Despite the identification of pathogenic driver mutations, it is now recognized that these mutations may not be sufficient for gliomagenesis and clinical progression.
Article
Oncology
Amanda De Andrade Costa, Jit Chatterjee, Olivia Cobb, Shilpa Sanapala, Suzanne Scheaffer, Xiaofan Guo, Sonika Dahiya, David H. Gutmann
Summary: The study identified ITGAL/CD11A as a critical microglia regulator of LGG biology, with implications for future stroma-targeted brain tumor treatment strategies.
Article
Cell Biology
Corina Anastasaki, Paola Orozco, David H. Gutmann
Summary: Neurofibromatosis type 1 is a rare neurogenetic syndrome caused by mutations in the NF1 gene. The encoded protein, neurofibromin, functions as a negative regulator of RAS activity. However, neurofibromin may have additional functions beyond the canonical RAS pathway regulation.
DISEASE MODELS & MECHANISMS
(2022)
Article
Multidisciplinary Sciences
Jit Chatterjee, Shilpa Sanapala, Olivia Cobb, Alice Bewley, Andrea K. Goldstein, Elizabeth Cordell, Xia Ge, Joel R. Garbow, Michael J. Holtzman, David H. Gutmann
Summary: Through leveraging mouse models and RNAseq data, this study demonstrates a potential mechanistic etiology for the reduced incidence of brain tumors, specifically optic gliomas, in children with asthma. Experimental asthma induction leads to decreased glioma formation and growth in Neurofibromatosis type 1 associated low grade optic glioma models, attributed to T cell-dependent inhibition of microglia-mediated tumor support.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Elizabeth C. Cordell, Mahmoud S. Alghamri, Maria G. Castro, David H. Gutmann
Summary: The brain tumor microenvironment contains various nonneoplastic cells, which play important roles in the formation and progression of brain cancers. This review discusses the roles of T cells in low- and high-grade glioma formation and progression, as well as the potential uses of modified T lymphocytes for brain cancer therapeutics.
Article
Multidisciplinary Sciences
Corina Anastasaki, Juan Mo, Ji-Kang Chen, Jit Chatterjee, Yuan Pan, Suzanne M. Scheaffer, Olivia Cobb, Michelle Monje, Lu Q. Le, David H. Gutmann
Summary: Neuronal activity plays a crucial role in central and peripheral nervous system cancers. NF1 mutations modify tumor predisposition by increasing neuronal excitability and activity-regulated paracrine factor production. In mouse models, reduced HCN channel function driven by Nf1 mutations leads to tumor growth in both central and peripheral nervous system.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Alice F. Bewley, Titilope M. Akinwe, Tychele N. Turner, David H. Gutmann
Summary: NF1 variants in sporadic tumors differ from those in NF1 individuals in terms of type, location, and pathogenicity. Many NF1 variants in sporadic cancers are not pathogenic and may be passenger variants or hypomorphic alleles. Further research is needed to define their roles in nonsyndromic cancer.
NEUROLOGY-GENETICS
(2022)
Article
Oncology
Till Milde, Jason Fangusaro, Michael J. Fisher, Cynthia Hawkins, Fausto J. Rodriguez, Uri Tabori, Olaf Witt, Yuan Zhu, David H. Gutmann
Summary: Pediatric low-grade gliomas (pLGGs) are common brain tumors in young children, which often result in chronic tumor- and therapy-related morbidities. The growth of pLGGs is influenced by genetic alterations and nonneoplastic cells in the microenvironment. Preclinical models are necessary to identify potential drugs for clinical evaluation and improve treatment for children with pLGGs.
Editorial Material
Medicine, Research & Experimental
David H. Gutmann
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Review
Oncology
Yunshuo Tang, David H. Gutmann
Summary: Optic pathway glioma (OPG) occurs in a significant number of individuals with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome. While often benign and slow growing, some patients with NF1-OPGs experience symptoms such as vision loss and precocious puberty. Studies using genetically engineered Nf1-OPG mouse models have provided valuable insights into the molecular and cellular pathways of optic gliomagenesis and identified potential new treatments. Research focusing on determining the factors underlying optic glioma development and tumor-induced optic nerve injury will contribute to personalized risk assessment and improved treatment for children with NF1-OPG.
CANCER MANAGEMENT AND RESEARCH
(2023)
Article
Oncology
Nicole M. Brossier, Jennifer M. Strahle, Samuel J. Cler, Michael Wallendorf, David H. Gutmann
NEURO-ONCOLOGY ADVANCES
(2022)
