Article
Urology & Nephrology
Kathrin Burgmaier, Leonie Brinker, Florian Erger, Bodo B. Beck, Marcus R. Benz, Carsten Bergmann, Olivia Boyer, Laure Collard, Claudia Dafinger, Marc Fila, Claudia Kowalewska, Baerbel Lange-Sperandio, Laura Massella, Antonio Mastrangelo, Djalila Mekahli, Monika Miklaszewska, Nadina Ortiz-Bruechle, Ludwig Patzer, Larisa Prikhodina, Bruno Ranchin, Nadejda Ranguelov, Raphael Schild, Tomas Seeman, Lale Sever, Przemyslaw Sikora, Maria Szczepanska, Ana Teixeira, Julia Thumfart, Barbara Uetz, Lutz Thorsten Weber, Elke Wuehl, Klaus Zerres, Joerg Doetsch, Franz Schaefer, Max Christoph Liebau
Summary: ARPKD is a severe disease characterized by fibrocystic changes in kidneys and liver, caused by variants in the PKHD1 gene. A study identified new genotype-phenotype correlations, showing that different regions of the gene affect disease severity and outcomes, potentially guiding personalized treatment approaches.
KIDNEY INTERNATIONAL
(2021)
Article
Urology & Nephrology
Ramona Ajiri, Kathrin Burgmaier, Nurver Akinci, Ilse Broekaert, Anja Buescher, Ismail Dursun, Ali Duzova, Loai Akram Eid, Marc Fila, Michaela Gessner, Ibrahim Gokce, Laura Massella, Antonio Mastrangelo, Monika Miklaszewska, Larisa Prikhodina, Bruno Ranchin, Nadejda Ranguelov, Rina Rus, Lale Sever, Julia Thumfart, Lutz Thorsten Weber, Elke Wuehl, Alev Yilmaz, Joerg Doetsch, Franz Schaefer, Max Christoph Liebau
Summary: This study followed up 70 siblings from 35 families with autosomal recessive polycystic kidney disease (ARPKD) and found comparable clinical courses of kidney and liver diseases in most families. The data suggest a strong impact of the underlying genotype on clinical variability.
KIDNEY INTERNATIONAL REPORTS
(2022)
Review
Neurosciences
Rong Ma, Naseer A. Kutchy, Liang Chen, Douglas D. Meigs, Guoku Hu
Summary: This review discusses the role of primary cilia in brain disorders, highlighting aging as a major risk factor and examining various cellular and molecular events involved in the progression of these diseases.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Cell Biology
Sila Yanardag, Elena N. Pugacheva
Summary: Primary cilium plays a significant role in guiding stem cells during differentiation by controlling signal transduction and stability. Defects in primary cilia formation or dynamics can lead to various health problems, including obesity, cardiovascular and renal anomalies, hearing and vision loss, and even cancer.Future research should focus on exploring how primary cilium regulates different signaling pathways in stem cell differentiation.
Article
Biology
Katarzyna Szymanska, Karsten Boldt, Clare Logan, Matthew Adams, Philip A. Robinson, Marius Ueffing, Elton Zeqiraj, Gabrielle Wheway, Colin A. Johnson
Summary: This study provides mechanistic insight into ciliary ubiquitin processing and uncovers UBE2E1 and RNF34 as novel interactants of MKS1. UBE2E1 mediates both regulatory and degradative ubiquitination of MKS1, and phosphorylated beta-catenin processing occurs at the ciliary base.
Review
Medicine, Research & Experimental
Ina Ofelia Focsa, Magdalena Budisteanu, Mihaela Balgradean
Summary: Ciliopathies are a group of complex diseases involving multiple organs and systems. Research has shown that the pathogenesis of ciliopathies involves multiple genes, and predicting the disease phenotype remains a challenge.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Renshuai Zhang, Jianming Tang, Tianliang Li, Jun Zhou, Wei Pan
Summary: Primary cilia are mechanosensory organelles that regulate cellular physiological processes. INPP5E is an enzyme that plays a key role in phosphoinositide metabolism and works synergistically with ciliary membrane-related proteins to maintain cilia homeostasis and function.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Emily R. Moore
Summary: This article reviews the role of primary cilia in craniofacial abnormalities and examines the existing information on primary cilia in craniofacial development and repair. It is found that dysfunction of primary cilia directly leads to diseases and syndromes affecting multiple organ systems.
Article
Cell Biology
Ondrej Bernatik, Petra Paclikova, Anna Kotrbova, Vitezslav Bryja, Lukas Cajanek
Summary: Recent research shows that the WNT/beta-catenin signaling pathway is not generally required for efficient cilia formation and in some systems may even moderately suppress ciliogenesis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Sami Zaqout, Angela M. Kaindl
Summary: This review article provides an in-depth look into the microcephalic MCPH brain. The article discusses the cytoarchitecture of the cerebral cortex and various processes occurring at the level of neural progenitors, early generated and mature neurons, and glial cells. The aim is to give an overview of current knowledge in MCPH phenotype and normal brain growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Cell Biology
Silvia Marino
Summary: This article discusses the roles of primary cilia in molecularly distinct medulloblastoma subgroups, highlighting the importance of designing subgroup-specific therapeutic approaches.
GENES & DEVELOPMENT
(2022)
Review
Endocrinology & Metabolism
Eun Young Lee, Jing W. Hughes
Summary: Primary cilia are important organelles on the surfaces of most eukaryotic cells that play a role in development and signaling pathways. Dysfunction of cilia is associated with human developmental and genetic disorders, including obesity and diabetes. This article reviews the expression and function of cilia in pancreatic islet cells and discusses the role of cilia in glucose homeostasis and human diseases.
DIABETES & METABOLISM JOURNAL
(2023)
Article
Cell Biology
Jie Xu, Xiaoyan Deng, Xiangmei Wu, Huifang Zhu, Yinghua Zhu, Jie Liu, Qian Chen, Chengfu Yuan, Geli Liu, Changdong Wang
Summary: This study found that gastric cancer may cause bone damage prior to bone metastasis, possibly through cilia-dependent activation of the Wnt/beta-catenin signaling pathway as indicated by clinical evidence and mouse model experiments.
Review
Pediatrics
Max Christoph Liebau
Summary: ARPKD, a rare disorder in pediatric nephrology, is mainly caused by variants in the PKHD1 gene and presents major clinical variability. Symptoms frequently appear perinatally, posing challenges in management. This review focuses on early manifestations and clinical management, particularly on kidney disease.
PEDIATRIC NEPHROLOGY
(2021)
Article
Cell Biology
Yong Ha Youn, Shirui Hou, Chang-Chih Wu, Daisuke Kawauchi, Brent A. Orr, GilesW. Robinson, David Finkelstein, Makoto M. Taketo, Richard J. Gilbertson, Martine F. Roussel, Young-Goo Han
Summary: This study reveals that primary cilia have different functions in different types of tumors and uncovers the molecular mechanisms underlying their involvement in tumorigenesis.
GENES & DEVELOPMENT
(2022)
Article
Genetics & Heredity
Sunayna Best, Jenny Lord, Matthew Roche, Christopher M. Watson, James A. Poulter, Roel P. J. Bevers, Alex Stuckey, Katarzyna Szymanska, Jamie M. Ellingford, Jenny Carmichael, Helen Brittain, Carmel Toomes, Chris Inglehearn, Colin A. Johnson, Gabrielle Wheway
Summary: This study linked large-scale genome sequence with phenotype information to achieve a molecular diagnosis for 51.8% of probands suspected to have primary ciliopathies, higher than previously reported. A significant proportion of diagnoses were due to variants in non-ciliopathy disease genes, indicating clinical difficulties in recognizing ciliopathies.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Multidisciplinary Sciences
Louise Richardson, Dapeng Wang, Ruth Hughes, Colin A. Johnson, Michelle Peckham
Summary: Skeletal muscle satellite cells cultured on soft surfaces show improved differentiation compared to those cultured on stiff surfaces. The study found that proliferating cells on soft surfaces express Pax3 instead of Pax7, but still undergo normal differentiation into myotubes. Additionally, cells on soft surfaces showed higher expression levels of myogenic regulatory factors, sarcomeric genes, enhanced fusion, and improved myofibrillogenesis. This comprehensive RNA-Seq dataset provides valuable insights into Pax3 expressing cells and their differentiation process.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Katarzyna Szymanska, Karsten Boldt, Clare Logan, Matthew Adams, Philip A. Robinson, Marius Ueffing, Elton Zeqiraj, Gabrielle Wheway, Colin A. Johnson
Summary: This study provides mechanistic insight into ciliary ubiquitin processing and uncovers UBE2E1 and RNF34 as novel interactants of MKS1. UBE2E1 mediates both regulatory and degradative ubiquitination of MKS1, and phosphorylated beta-catenin processing occurs at the ciliary base.
Editorial Material
Genetics & Heredity
Sunayna Best, Chris F. Inglehearn, Christopher M. Watson, Carmel Toomes, Gabrielle Wheway, Colin A. Johnson
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Marilena Elpidorou, James A. Poulter, Katarzyna Szymanska, Wia Baron, Katrin Junger, Karsten Boldt, Marius Ueffing, Lydia Green, John H. Livingston, Eammon G. Sheridan, Colin A. Johnson
Summary: This study found that a mutation in the MAL gene can cause a hypomyelinating leukodystrophy similar to Pelizaeus-Merzbacher disease. The mutant MAL gene affects the distribution of PLP1, leading to abnormal development of cerebral white matter.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Oncology
Maria Georgiou, Chunbo Yang, Robert Atkinson, Kuan-Ting Pan, Adriana Buskin, Marina Moya Molina, Joseph Collin, Jumana Al-Aama, Franziska Goertler, Sebastian E. J. Ludwig, Tracey Davey, Reinhard Luhrmann, Sushma Nagaraja-Grellscheid, Colin A. Johnson, Robin Ali, Lyle Armstrong, Viktor Korolchuk, Henning Urlaub, Sina Mozaffari-Jovin, Majlinda Lako
Summary: Mutations in PRPF31, a core protein of the spliceosomal tri-snRNP complex, cause autosomal-dominant retinitis pigmentosa (adRP). This study used iPSC technology to generate retinal organoids and RPE models from PRPF31-adRP patients, and found that RNA splicing, autophagy and lysosome, and visual cycle pathways were significantly affected. The accumulation of cytoplasmic aggregates and impaired waste disposal mechanisms were also observed in patient-derived cells. Activation of the autophagy pathway reduced the aggregates and improved cell survival.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Sunayna Best, Jing Yu, Jenny Lord, Matthew Roche, Christopher Mark Watson, Roel P. J. Bevers, Alex Stuckey, Savita Madhusudhan, Rosalyn Jewell, Sanjay M. Sisodiya, Siying Lin, Stephen Turner, Hannah Robinson, Joseph S. Leslie, Emma Baple, Carmel Toomes, Chris Inglehearn, Gabrielle Wheway, Colin A. Johnson
Summary: Reverse phenotyping improves the rate of successful molecular diagnosis for patients with primary ciliopathies. Previous analyses may have missed these diagnoses due to incomplete clinical data, highlighting the importance of better phenotyping for accurate diagnosis and improved patient outcomes.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Engineering, Biomedical
Fatmah I. Ghuloum, Colin A. Johnson, Natalia A. Riobo-Del Galdo, Mahetab H. Amer
Summary: This review provides an overview of the role of Hedgehog signalling and mechanobiology in bone development and regeneration, highlighting the importance of Hedgehog signalling pathway response to mechanical cues in bone marrow-derived mesenchymal stromal cells and osteogenesis. Different tissue engineering strategies are proposed to apply the knowledge of 3D material-cell interactions in the modulation of Hedgehog signalling for research applications.
MATERIALS TODAY BIO
(2022)
Article
Multidisciplinary Sciences
Ida Signe Bohse Larsen, Lorenzo Povolo, Luping Zhou, Weihua Tian, Kasper Johansen Mygind, John Hintze, Chen Jiang, Verity Hartill, Katrina Prescott, Colin A. Johnson, Sureni V. Mullegama, Allyn McConkie-Rosell, Marie McDonald, Lars Hansen, Sergey Y. Vakhrushev, Katrine T. Schjoldager, Henrik Clausen, Thomas Worzfeld, Hiren J. Joshi, Adnan Halim
Summary: Mutations in the TMEM260 gene cause heart defects and renal anomalies syndrome. The TMEM260 gene encodes an ER-located protein O-mannosyltransferase that selectively glycosylates IPT domains. Disease-causing TMEM260 mutations impair O-mannosylation of IPT domains and result in receptor matura-tion defects and abnormal growth of 3D cell models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Genetics & Heredity
Basudha Basu, Alice V. R. Lake, Becky China, Katarzyna Szymanska, Gabrielle Wheway, Sandra Bell, Ewan Morrison, Jacquelyn Bond, Colin A. Johnson
Summary: This study re-analyzed a genetic screen to identify the mechanisms behind aberrant formation of supernumerary primary cilia in mammalian cells. RACGAP1 was identified as the strongest candidate hit. The results showed that cytokinesis failure led to the formation of supernumerary cilia, and this has functional implications in diseases marked by centrosomal amplification.
ANNALS OF HUMAN GENETICS
(2023)
Article
Materials Science, Biomaterials
Fatmah I. Ghuloum, Lee A. Stevens, Colin A. Johnson, Natalia A. Riobo-Del Galdo, Mahetab H. Amer
Summary: This study proposes a mechanism linking the activation of Hedgehog signalling to the osteoinductive effect of surface-engineered, topographically-textured polymeric microparticles. The researchers found that the topographical microenvironment plays a role in modulating Hedgehog signalling and inducing osteogenesis in mesenchymal stem cells. This study highlights the potential for tailoring substrate topographical design to offer cell-instructive 3D microenvironments.
BIOMATERIALS ADVANCES
(2023)
Meeting Abstract
Ophthalmology
Maria Georgiou, Chunbo Yang, Robert Atkinson, Kuan-Ting Pan, Adriana Buskin, Marina Moya Molina, Joseph Collin, Sebastian E. J. Ludwig, Sushma Nagaraja-Grellscheid, Colin Johnson, Robin Ali, Lyle Armstrong, Viktor Korolchuk, Henning Urlaub, Sina Mozaffari-Jovin, Majlinda Lako
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Meeting Abstract
Ophthalmology
Rob Atkinson, Chunbo Yang, Katarzyna Szymanska, Maria Georgiou, Chia Beh, Joseph Collin, Marina Moya Molina, Ross Laws, Sina Mozaffari-Jovin, Colin Johnson, Majlinda Lako
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Evangelia S. Panagiotou, Narcis Fernandez-Fuentes, Layal Abi Farraj, Martin McKibbin, Nursel H. Elcioglu, Hussain Jafri, Eren Cerman, David A. Parry, Clare V. Logan, Colin A. Johnson, Chris F. Inglehearn, Carmel Toomes, Manir Ali
Summary: This study aimed to investigate the molecular basis of recessively inherited congenital cataract, microcornea, and corneal opacification. Through analysis using methods such as autozygosity mapping and whole-exome sequencing, mutations in the SIX6 gene were found to be associated with the occurrence of ocular diseases.
Article
Pediatrics
Dirk E. Schrander, Heleen M. Staal, Colin A. Johnson, Alistair Calder, Neeti Ghali, Albert E. Chudley, Constance T. R. M. Stumpel
Summary: SAMS syndrome is an ultra-rare developmental disorder characterized by short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities. Only four affected individuals have been reported to date. The syndrome includes orthopaedic diagnoses such as scapulohumoral synostosis and bilateral congenital ventral dislocation of the hips. Therefore, SAMS syndrome should be considered as the primary diagnosis when bilateral congenital ventral dislocation of the hips and/or scapulohumoral synostosis are found or suspected.
JOURNAL OF PEDIATRIC GENETICS
(2022)