Article
Biochemistry & Molecular Biology
Huanxian Wu, Lishun Zhang, Boyu Chen, Baofang Ou, Jiahuan Xu, Nannan Tian, Danni Yang, Yangcheng Ai, Qianqing Chen, Dongling Quan, Tingting Zhang, Lin Lv, Yuanxin Tian, Jiajie Zhang, Shaoyu Wu
Summary: B13 is an effective drug that inhibits the proliferation and metastasis of colorectal cancer cells, inducing cell cycle arrest and apoptosis. It has low toxicity and superior antitumor activity compared to Vismodegib. By binding to Smo protein, B13 inhibits the expression of downstream gene Gli1 and its localization in the nucleus, overcoming resistance caused by SmoD473H mutations.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Junwan Fan, Haowen Li, Lun Kuang, Zichen Zhao, Wenyan He, Chen Liu, Yongjun Wang, Steven Y. Cheng, Wei Chen
Summary: A new Smoothened inhibitor, 0025A, has been discovered in this study, which effectively targets the Hedgehog signaling pathway and inhibits cancer cell activity. Additionally, it can suppress hair growth in mice.
CELL AND BIOSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Zhi-Ping Qiu, Ao Hu, Bao-Liang Song
Summary: The study identified Emopamil binding protein (EBP) as a protein that interacts with SMO, suppressing SMO cholesterylation and Hh pathway activity. EBP modulates SMO cholesterylation through direct binding, providing insights into the potential mechanism of CDPX2 pathogenesis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Review
Cell Biology
Jianhang Jia, Jin Jiang
Summary: This review focuses on the essential role of Smoothened (Smo) protein in Hedgehog (Hh) signal transduction, as well as the regulatory mechanisms of Smo endocytosis and degradation in both insects and vertebrates. It discusses how Hh inhibits Smo ubiquitination and promotes Smo surface/ciliary accumulation through ubiquitin-specific protease 8 (USP8) in Drosophila, and also highlights the induction of sumoylation by Hh in regulating Smo trafficking and abundance in both Drosophila and mammalian cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Diana C. Yanez, Eleftheria Papaioannou, Mira M. Chawda, Jasmine Rowell, Susan Ross, Ching-In Lau, Tessa Crompton
Summary: Pharmacological inhibition of smoothened reduces Th2 cell infiltration and alleviates the severity of allergic asthma by decreasing the induction of Shh, IL-4, and IL-13, as well as lowering serum IgE levels and expression of inflammation-related genes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Deborah Quaglio, Paola Infante, Silvia Cammarone, Lara Lamelza, Marilisa Conenna, Francesca Ghirga, Gennaro Adabbo, Luca Pisano, Lucia Di Marcotullio, Bruno Botta, Mattia Mori
Summary: Natural products with chemical diversity and ability to modulate biological systems are important in the design of novel bioactive compounds. This study reports the successful rational design and synthesis of anthraquinone-based hybrids as inhibitors of the Hedgehog (HH) signalling pathway, which plays a significant role in anticancer therapy. The findings provide new insights into the design principles for the development of novel natural product-based inhibitors.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Cell Biology
Jie Zhang, Zulong Liu, Jianhang Jia
Summary: SMO, a seven-transmembrane protein critical for hedgehog signal transduction, is regulated by multiple post-translational modifications and small molecules to maintain its activity balance and impact developmental defects and cancer initiation.
Review
Biochemistry & Molecular Biology
Jian Yi Chai, Vaisnevee Sugumar, Mohammed Abdullah Alshawsh, Won Fen Wong, Aditya Arya, Pei Pei Chong, Chung Yeng Looi
Summary: The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved in mammals and plays crucial roles in cancer initiation and progression. GLI transcription factors are regulated by both SMO-dependent and SMO-independent mechanisms, with dysregulation leading to tumorigenesis in various cancers. Understanding the complex interplay between GLI and signaling elements could inspire new therapeutic breakthroughs for Hh-GLI-dependent cancers.
Article
Biology
Marina Goncalves Antunes, Matthieu Sanial, Vincent Contremoulins, Sandra Carvalho, Anne Plessis, Isabelle Becam
Summary: This study reveals how the hedgehog (HH) morphogen regulates the subcellular localization and activity of the oncogenic G-protein-coupled receptor (GPCR) Smoothened (SMO), thereby affecting the morphogenesis of epithelial structures. The authors provide evidence that HH promotes the recycling of internalized SMO, leading to its stabilization. This effect relies on the action of protein kinase A, casein kinase I, and Fused (FU) kinase. Additionally, at high HH levels, FU leads to the local enrichment of SMO in the basal domain of the cell membrane.
Review
Immunology
Yazhen Su, Hao Xing, Jie Kang, Linkun Bai, Liyun Zhang
Summary: The Hedgehog (Hh) signaling pathway plays a crucial role in rheumatic diseases and has the potential to be a therapeutic target.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Alice Del Giovane, Mariagiovanna Russo, Linda Tirou, Helene Faure, Martial Ruat, Sonia Balestri, Carola Sposato, Francesco Basoli, Alberto Rainer, Abdelmoumen Kassoussi, Elisabeth Traiffort, Antonella Ragnini-Wilson
Summary: This study shows that non-canonical signaling pathways can promote the maturation and regeneration of myelin cells, suggesting a potential role in the treatment of demyelinating diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Physiology
Mira Hamze, Igor Medina, Quentin Delmotte, Christophe Porcher
Summary: GABA plays a crucial role in the early stages of central nervous system development, with KCC2 and Shh-Smo signaling pathways impacting chloride ion balance and GABA function.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Junwan Fan, Zichen Zhao, Ru Liu, Haowen Li, Wenyan He, Jianping Wu, Yongjun Wang, Wei Chen
Summary: Our study found that the new Smoothened inhibitor TT22 can effectively block the translocation of β-arrestin2-GFP to Smoothened in neurons, reduce the accumulation of Smoothened on primary cilia, and inhibit the expression of downstream Gli transcription factor. In addition, TT22 also inhibits abnormal seizure-like activity in neurons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Wanchen Wang, Ryo Shiraishi, Daisuke Kawauchi
Summary: The sonic hedgehog (SHH) pathway plays a crucial role in regulating the development of the central nervous system in vertebrates, and aberrant regulation can lead to neurodevelopmental diseases and brain tumors. Research on the mechanisms of SHH in the cerebellum has shed light on structural abnormalities and medulloblastoma, with current clinical trials exploring novel therapeutic approaches.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Developmental Biology
Wenguang Yin, Andreas Liontos, Janine Koepke, Maroua Ghoul, Luciana Mazzocchi, Xinyuan Liu, Chunyan Lu, Haoyu Wu, Athanasios Fysikopoulos, Alexandros Sountoulidis, Werner Seeger, Clemens Ruppert, Andreas Gunther, Didier Y. R. Stainier, Christos Samakovlis
Summary: The tracheal epithelium is a crucial element in pulmonary diseases, and its understanding of cell proliferation and differentiation is limited. The Hedgehog (HH) signaling pathway plays a role in communication between epithelial and mesenchymal cells in the lung, affecting stromal cell proliferation, differentiation, and epithelial signaling. This study discovered an autocrine HH signaling function in airway epithelial cells, with its inhibition leading to defects in cell proliferation and differentiation. Additionally, HH function is mediated by transcriptional activation, as inhibition of HH signaling downregulates cell type-specific transcription factor genes in both mouse trachea and human airway epithelial cells. These findings provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.
Article
Public, Environmental & Occupational Health
Bin Yu, Igor Akushevich, Arseniy P. Yashkin, Anatoliy Yashin, H. Kim Lyerly, Julia Kravchenko
Summary: There are significant geographic disparities in heart failure outcomes among older adults in the United States, with lagging states having higher incidence, prevalence, and mortality rates, as well as lower survival rates compared to leading states. Recent trends show an increase in heart failure incidence and a decline in survival rates, highlighting the importance of prevention strategies.
Editorial Material
Oncology
John T. Schiller, Douglas R. Lowy
Summary: Given the renewed interest in vaccine development sparked by the COVID-19 pandemic, this article revisits the current state of vaccine development for cancer prevention and treatment. Experts discuss different vaccine types, their antigens and modes of action, and provide insights into the clinical development progress and challenges that need to be overcome for wide implementation.
Article
Multidisciplinary Sciences
Clare A. Rebbeck, Jian Xian, Susanne Bornelov, Joseph Geradts, Amy Hobeika, Heather Geiger, Jose Franco Alvarez, Elena Rozhkova, Ashley Nicholls, Nicolas Robine, Herbert K. Lyerly, Gregory J. Hannon
Summary: Ductal carcinoma in situ (DCIS) is a non-invasive precursor to breast cancer, and the progression to invasive ductal carcinoma (IDC) is not well understood. Gene expression analysis reveals a progressive loss in basal layer integrity and two epithelial to mesenchymal transitions during the progression from DCIS to IDC. Potential biomarkers associated with this progression have been identified.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Kensuke Kaneko, Chaitanya R. Acharya, Hiroshi Nagata, Xiao Yang, Zachary Conrad Hartman, Amy Hobeika, Philip F. Hughes, Timothy A. J. Haystead, Michael A. Morse, Herbert Kim Lyerly, Takuya Osada
Summary: Combining HS201-PDT with anti-PD-L1 antibody showed enhanced antitumor activity, upregulated CXCR3 gene signature, and improved tumor infiltration by T cells, suggesting the potential of HS201-PDT combined with PD-1/PD-L1 blockade as a treatment strategy for breast cancer. Receptor-ligand interactome analysis revealed enhanced signaling pathways associated with CD8+T cell activation in the combination group.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Kensuke Kaneko, Hiroshi Nagata, Xiao-Yi Yang, Joshua Ginzel, Zachary Hartman, Jeffrey Everitt, Philip Hughes, Timothy Haystead, Michael Morse, Herbert Kim Lyerly, Takuya Osada
Summary: The study evaluated the efficacy of Hsp90-targeted photodynamic therapy (HS201-PDT) as a non-surgical alternative treatment for DCIS. The findings showed that HS201-PDT significantly improved disease-free survival and combining it with anti-PD-L1 antibodies enhanced the treatment effect, indicating its potential as a promising treatment strategy.
Review
Biotechnology & Applied Microbiology
Michael A. Morse, Erika J. Crosby, Jeremy Force, Takuya Osada, Amy C. Hobeika, Zachary C. Hartman, Peter Berglund, Jonathan Smith, H. Kim Lyerly
Summary: Therapeutic cancer vaccines use different platforms, such as messenger RNAs (mRNA), for antigen delivery. Self-replicating RNAs (srRNA) increase epitope expression and have been derived from positive-strand RNA viruses. Clinical stage srRNA vectors have shown positive results in encoding tumor antigens and adverse events have been minimal. Recent development of fully synthetic srRNA technologies shows promise for future vaccines.
CANCER GENE THERAPY
(2023)
Editorial Material
Biotechnology & Applied Microbiology
Herbert Kim Lyerly
CANCER GENE THERAPY
(2023)
Editorial Material
Oncology
Erika J. Crosby, Zachary C. Hartman, H. Kim Lyerly
Summary: A vaccine targeted at HER2 can prime T cells for ex vivo expansion and adoptive transfer with minimal toxicity. This treatment modality can lead to intramolecular epitope spreading in most patients and potentially improve outcomes for patients with metastatic HER2-positive breast cancer.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Takuya Osada, Xiaoning Jiang, Yuhang Zhao, Mengyue Chen, Benjamin C. Kreager, Huaiyu Wu, Howuk Kim, Jun Ren, Joshua Snyder, Pei Zhong, Michael A. Morse, H. Kim Lyerly
Summary: Mechanical high-intensity focused ultrasound (M-HIFU), including histotripsy, is a non-invasive and non-thermal ablation technology that has shown initial safety and efficacy in treating malignant liver tumors. In addition to tissue ablation, M-HIFU has the potential to stimulate local and systemic antitumor immune response in preclinical models and clinical trials.
INTERNATIONAL JOURNAL OF HYPERTHERMIA
(2023)
Article
Medicine, Research & Experimental
Timothy N. Trotter, Carina E. Dagotto, Delila Serra, Tao Wang, Xiao Yang, Chaitanya R. Acharya, Junping Wei, Gangjun Lei, H. Kim Lyerly, Zachary C. Hartman
Summary: This study reveals that dormant tumor cells can evade immune detection by utilizing tolerance mechanisms to alter the T cell microenvironment. The researchers found that dormant tumor cells can initiate immune responses but also promote the accumulation of regulatory T cells, inhibiting the activity of CD8+ killer T cells. Additionally, a protein called DKK3 derived from the tumor cells is critical for this suppression of the immune system and is associated with poor survival and immunosuppression in human breast cancers. Targeting these mechanisms, such as DKK3, may render dormant tumors susceptible to immunotherapies.
Meeting Abstract
Oncology
Zelanna Goldberg, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou, Jessica Sparks, Darina Spasova, Shigeki Miyake-Stoner, Christopher A. Rabiola, Erika J. Crosby, Zachary C. Hartman, Herbert K. Lyerly, Nathaniel Wang, Parinaz Aliahmad
Meeting Abstract
Oncology
Zelanna Goldberg, Christian Maine, Gabrielle P. Dailey, Christine Domingo, Gaelle Picarda, Hunter Little, Annie Chou, Jessica Sparks, Darina Spasova, Shigeki Miyake-Stoner, Zachary C. Hartman, Christopher A. Rabiola, Erika J. Crosby, Herbert K. Lyerly, Nathaniel Wang, Parinaz Aliahmad
Meeting Abstract
Oncology
Bin-Jin Hwang, Erika Crosby, Timothy Trotter, Li-Chung Tsao, Tao Wang, Xiao Yang, Herbert Kim Lyerly, Zachary Hartman
Meeting Abstract
Oncology
Timothy N. Trotter, Delila Serra, Carina Dagotto, Tao Wang, Xiao Yang, Junping Wei, Gangjun Lei, H. Kim Lyerly, Zachary C. Hartman
Review
Biotechnology & Applied Microbiology
Anchit Bhagat, Herbert K. Lyerly, Michael A. Morse, Zachary C. Hartman
Summary: This review summarizes the progress in the development of CEA vaccines, demonstrating their ability to elicit immune response and improve clinical outcomes, but further confirmation is needed.
HUMAN VACCINES & IMMUNOTHERAPEUTICS
(2023)
