Review
Cell Biology
Venturina Stagni, Alessandra Ferri, Claudia Cirotti, Daniela Barila
Summary: There is a strong interplay between autophagy and genomic stability, with recent evidence linking DNA Damage Response (DDR) and autophagy in influencing cell fate. ATM kinase plays a crucial role in balancing senescence and apoptosis in response to stimuli, and its aberrant deregulation is linked to the development of pathologies like cancer and neurodegeneration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Geraldine Blanchard-Rohner, Anna Peirolo, Ludivine Coulon, Christian Korff, Judit Horvath, Pierre R. Burkhard, Fabienne Gumy-Pause, Emmanuelle Ranza, Peter Jandus, Harpreet Dibra, Alexander Malcolm R. Taylor, Joel Fluss
Summary: Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder characterized by various symptoms. This study presents a case series highlighting the phenotypic variability of A-T and emphasizes the importance of early diagnosis of variant A-T and classical A-T.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sapir Schlam-Babayov, Ariel Bensimon, Michal Harel, Tamar Geiger, Ruedi Aebersold, Yael Ziv, Yosef Shiloh
Summary: This study conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells to reveal the fine-tuned dynamics and relationships between PIKKs in the response to genotoxic stress. The results highlight the complex interactions among ATM, ATR, and DNA-PK in the DDR.
Article
Immunology
Ruth Pia Duecker, Lucia Gronau, Patrick C. Baer, Stefan Zielen, Ralf Schubert
Summary: Our study focused on investigating the feasibility of different approaches of hematopoietic stem cell transplantation (HSCT) for Ataxia-telangiectasia (A-T) by using Atm-deficient mice as models. The results showed that haploidentical HSCT could extend the lifespan of Atm-deficient mice and improve T-cell numbers and functionality. Interestingly, HSCT using heterozygous donor cells also led to improved survival and enhanced CD4 cell functionality in Atm-deficient mice, suggesting it as a potential strategy for A-T treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Mohammad Z. Islam, Xinggui Shen, Sibile Pardue, Christopher B. Pattillo, Christopher G. Kevil, Rodney E. Shackelford
Summary: The ATM protein plays a crucial role in regulating cell cycle checkpoints, cellular redox state, and DNA repair. Its loss in ataxia-telangiectasia (A-T) leads to symptoms such as ataxia, telangiectasias, dysregulated redox and iron responses, and increased cancer risk. Our study reveals that ATM regulates the sulfur pool, Fe-S cluster biosynthesis, transsulfuration pathway, and glutathione redox cycling, which may explain some of the redox- and iron-related pathologies seen in A-T.
Article
Oncology
Michael J. Hall, Ryan Bernhisel, Elisha Hughes, Katie Larson, Eric T. Rosenthal, Nanda A. Singh, Johnathan M. Lancaster, Allison W. Kurian
Summary: This study estimated cancer risks associated with ATM pathogenic variants independently of family history, showing that some variants may have higher breast cancer risks than previously recognized. Increased screening for prostate and gastric cancer may be warranted for carriers of ATM pathogenic variants.
CANCER PREVENTION RESEARCH
(2021)
Article
Oncology
Madeline B. Torres, Laurence P. Diggs, Jun S. Wei, Javed Khan, Markku Miettinen, Grace-Ann Fasaye, Andy Gillespie, Brigitte C. Widemann, Rosandra N. Kaplan, Jeremy L. Davis, Jonathan M. Hernandez, Jaydira Del Rivero
Summary: Adrenocortical carcinoma (ACC) is a rare malignancy originating from the adrenal cortex, and surgery is currently the only curative option. This study reports a pathogenic variant in the ATM gene in a patient with ACC, suggesting a potential pathogenic role of ATM gene in certain ACC cases.
Review
Biochemistry & Molecular Biology
Laura A. Huff, Shan Yan, Mark G. Clemens
Summary: Cells have evolved extensive signaling mechanisms to maintain redox homeostasis, with a critical role of oxidants in normal signaling. However, excessive oxidants can lead to elevated oxidative stress, causing alterations in cellular operations and damage to cellular components. The cellular response to oxidative stress includes redox sensors that regulate the DNA damage response and orchestrated changes to the epigenome, protecting and regulating the nuclear genome.
Article
Multidisciplinary Sciences
Changwei Chen, Jennifer R. Gallagher, Jamie Tarlton, Lidy van Aalten, Susan E. Bray, Michael L. J. Ashford, Rory J. McCrimmon, Ewan R. Pearson, Alison D. McNeilly, Calum Sutherland
Summary: Genotype may influence the therapeutic effects of metformin for type-2 diabetes, and the NPAT gene may play a role in the mechanism of metformin action.
Review
Cell Biology
Yulia Mitiagin, Ari Barzilai
Summary: The review summarizes accumulating evidence that ataxia-telangiectasia mutated kinase is crucial for maintaining cellular homeostasis and has both nuclear and cytoplasmic functions. However, the specific functions of ataxia-telangiectasia mutated that lead to cerebellar degeneration when lost are still unknown. The review discusses the role of ataxia-telangiectasia mutated in cerebellar pathology, including its nuclear functions in DNA damage response circuits and its cytoplasmic and mitochondrial functions related to cellular homeostasis.
NEURAL REGENERATION RESEARCH
(2023)
Article
Medical Laboratory Technology
Chunyu Gu, Hong Wang, Jianbo Shu, Jie Zheng, Dong Li, Chunquan Cai, Peiyuan Zhang
Summary: This study described atypical symptoms of A-T in a 5-year-old girl and proposed a dual-omics diagnostic approach combining RNA-seq with WES. The study also discussed phenotypic heterogeneity of A-T among family members and individuals.
CLINICA CHIMICA ACTA
(2021)
Article
Immunology
Maria Giovanna Desimio, Andrea Finocchi, Gigliola Di Matteo, Silvia Di Cesare, Carmela Giancotta, Francesca Conti, Luciana Chessa, Maria Piane, Davide Montin, Marta Dellepiane, Paolo Rossi, Caterina Cancrini, Margherita Doria
Summary: NK cells in A-T patients show reduced NKG2D expression, possibly contributing to increased susceptibility. The abnormal expression of NKG2D in A-T patients may be associated with disease progression.
CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Yousra Ajouaou, Elena Magnani, Bhavani Madakashira, Eleanor Jenkins, Kirsten C. Sadler
Summary: Research on zebrafish demonstrates that overexpression of the UHRF1 gene causes a small liver, while mutation of the Atm gene exacerbates this phenomenon. It is also found that oxidative stress is one of the causes of the small liver, and the Atm gene can alleviate the effects of this stress.
Review
Genetics & Heredity
Motohiro Yamauchi
Summary: Chromosome rearrangements are structural variations in chromosomes and are associated with a variety of human diseases. Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by chromosome rearrangements at the cellular level, particularly in T lymphocytes. The defective gene in A-T is ataxia-telangiectasia mutated (ATM), which plays a central role in cellular response to DNA damage, including suppressing chromosome rearrangements.
Article
Neurosciences
Hadar Levi, Ela Bar, Stav Cohen-Adiv, Suzan Sweitat, Sivan Kanner, Ronit Galron, Yulia Mitiagin, Ari Barzilai
Summary: Ataxia-telangiectasia (A-T) is a genetic disease characterized by cerebellar issues and immune deficiency. Recent research suggests that specific vulnerabilities of cerebellar microglia may play a key role in the pathogenesis of A-T.
Article
Biochemistry & Molecular Biology
Alice Guazzelli, Parisa Meysami, Emyr Bakker, Constantinos Demonacos, Antonio Giordano, Marija Krstic-Demonacos, Luciano Mutti
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Biology
James A. L. Brown
JOURNAL OF BIOLOGICAL EDUCATION
(2020)
Article
Oncology
Richa Garva, Chutamas Thepmalee, Umpa Yasamut, Sangkab Sudsaward, Alice Guazzelli, Ramkumar Rajendran, Nopprarat Tongmuang, Sasiprapa Khunchai, Parisa Meysami, Thawornchai Limjindaporn, Pa-thai Yenchitsomanus, Luciano Mutti, Marija Krstic-Demonacos, Constantinos Demonacos
FRONTIERS IN ONCOLOGY
(2019)
Article
Oncology
Andrew McGuire, Maire-Caitlin Casey, Ronan M. Waldron, Helen Heneghan, Olga Kalinina, Emma Holian, Ailbhe McDermott, Aoife J. Lowery, John Newell, Roisin M. Dwyer, Nicola Miller, Maccon Keane, James A. L. Brown, Michael J. Kerin
Article
Oncology
Rashed Alhammad, Sasiprapa Khunchai, Nopprarat Tongmuang, Thawornchai Limjindaporn, Pa-Thai Yenchitsomanus, Luciano Mutti, Marija Krstic-Demonacos, Constantinos Demonacos
Article
Biochemistry & Molecular Biology
Hasen Alhebshi, Kun Tian, Lipsita Patnaik, Rebecca Taylor, Pavel Bezecny, Callum Hall, Patricia Anthonia Johanna Muller, Nazila Safari, Delta Patricia Menendez Creamer, Constantinos Demonacos, Luciano Mutti, Mohamad Nidal Bittar, Marija Krstic-Demonacos
Summary: Mutations in the p53 tumor suppressor gene are common in over 50% of cancers. This study found significant associations between p53 modifications, including acetylated p53 at K382, phosphorylated p53 at S46, and TTC5 protein, with tumor grade and overall survival in lung cancer patients. The results suggest that analyzing p53 modifications and TTC5 expression could be useful prognostic factors or drug targets for lung cancer treatment when tested on a larger patient sample size.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Emyr Yosef Bakker, Masayuki Fujii, Marija Krstic-Demonacos, Constantinos Demonacos, Rashed Alhammad
Summary: The study reveals the differential roles of PDIA1 in ERα-positive and ERα-negative breast cancer patients, providing insights into the pathways regulating carcinogenesis and potential therapeutic targets.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Review
Cell Biology
Li Chen, Xiangyi Kong, Yi Fang, Shishir Paunikar, Xiangyu Wang, James A. L. Brown, Emer Bourke, Xingrui Li, Jing Wang
Summary: Discoidin domain receptor tyrosine kinases (DDRs) are a type of receptor tyrosine kinases associated with various diseases, widely expressed in different cell types and involved in signaling pathways, closely related to the development and progression of solid tumors.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Amila Suraweera, James A. L. Brown, Yi Chieh Lim, Martin F. Lavin
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Editorial Material
Cell Biology
James A. L. Brown, E. Bourke, W. W. Hancock, D. J. Richard
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
James A. L. Brown
Summary: This study shows that academic staff in the biological sciences are eager to receive formal leadership skills training, but there is no clear evidence that they have received such training. The study also found that they are more interested in systemic leadership, which is lacking in the workplace. Therefore, specific leadership skills training should be incorporated into professional development programs in the field of biological sciences.
Article
Oncology
Amirhossein Jalali, David Miresse, Matthew R. Fahey, Niamh Ni Mhaonaigh, Andrew McGuire, Emer Bourke, Michael J. Kerin, James A. L. Brown
Summary: The study demonstrates the prognostic value of systemic blood-based immunocyte ratios in neoadjuvant chemotherapy-treated breast cancer patients, with significant associations found between different immunocyte ratios and subtype-specific outcomes.
Article
Pharmacology & Pharmacy
James A. L. Brown
PHARMACEUTICAL PATENT ANALYST
(2020)