Article
Biochemistry & Molecular Biology
Gregoire Andre, Antoine Chretien, Antoine Demoulin, Melanie Beersaerts, Pierre-Louis Docquier, Catherine Behets
Summary: This study investigates the organization of collagen and osteocyte lacunae in the long bones of mice with osteogenesis imperfecta (OI), a rare congenital bone disorder. The findings suggest that the alterations in collagen matrix and osteocyte lacunae organization contribute to bone fragility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Yoshiaki Miyake, Masanori Obana, Ayaha Yamamoto, Shunsuke Noda, Koki Tanaka, Hibiki Sakai, Narihito Tatsumoto, Chihiro Makino, Soshi Kanemoto, Go Shioi, Shota Tanaka, Makiko Maeda, Yoshiaki Okada, Kazunori Imaizumi, Katsuhiko Asanuma, Yasushi Fujio
Summary: Upregulation of OASIS in podocytes contributes to podocyte and/or tubular injury through decreased PRKCi expression and is a critical event for the disturbance of kidney homeostasis.
COMMUNICATIONS BIOLOGY
(2022)
Article
Endocrinology & Metabolism
Mathieu Simon, Michael Indermaur, Denis Schenk, Seyedmahdi Hosseinitabatabaei, Bettina M. Willie, Philippe Zysset
Summary: Osteogenesis Imperfecta (OI) is a genetic bone disorder characterized by impaired collagen synthesis, altered trabecular bone structure, and reduced bone mass. This study used HR-pQCT to compare the bone morphology of OI patients with healthy controls. The results showed that OI samples had significantly lower BV/TV and trabecular number, higher trabecular separation and standard deviation, but no difference in trabecular thickness compared to healthy controls. The stiffness analysis revealed that the fabric-elasticity relationships between OI and healthy individuals were similar when the ROIs were sufficiently homogeneous.
Article
Biochemistry & Molecular Biology
Antoine Chretien, Malory Couchot, Guillaume Mabilleau, Catherine Behets
Summary: Osteogenesis imperfecta (OI) is a genetic disorder characterized by low bone mass and spontaneous fractures. In a study using mice models, researchers found that the tendons and bones of OI mice showed altered biomechanical properties, structural changes, and modified tissue material properties. These findings provide valuable insights into the tendon ruptures and bone fragility observed in OI patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Matthias Maehr, Stephane Blouin, Martina Behanova, Barbara M. Misof, Francis H. Glorieux, Jochen Zwerina, Frank Rauch, Markus A. Hartmann, Nadja Fratzl-Zelman
Summary: The study revealed that there is a significant increase in osteocyte density in OI patients' bone tissue, while the OLS area slightly decreases in trabecular bone. Additionally, osteocyte density is positively correlated with bone formation parameters and negatively associated with osteoblast function indices.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Yasunao Kamikawa, Atsushi Saito, Koji Matsuhisa, Masayuki Kaneko, Rie Asada, Yasunori Horikoshi, Satoshi Tashiro, Kazunori Imaizumi
Summary: The nuclear envelope (NE) protects the genome and regulates genome activity, but can be damaged by stresses such as mechanical stress and cellular senescence, leading to a type of stress called NE stress. OASIS, an ER-resident transcription factor, accumulates at damaged NE, specifically among the OASIS family. OASIS mediates a novel NE stress response pathway by co-localizing with various components at the damaged NE and suppressing DNA damage induced by NE stress.
CELL DEATH DISCOVERY
(2021)
Article
Orthopedics
Bin Sun, Huiqiao Wu, Jiajia Lu, Rongcheng Zhang, Xiaolong Shen, Yifei Gu, Changgui Shi, Ying Zhang, Wen Yuan
Summary: The study showed that Irisin therapy reduced bone fracture risk in OI mice by promoting osteogenesis and counteracting TGF-beta/Smad signaling. This suggests the potential of using Irisin as a therapeutic reagent to prevent the progression of OI.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2023)
Review
Biochemistry & Molecular Biology
Victoria L. Gremminger, Charlotte L. Phillips
Summary: Bone and muscle tissues communicate extensively and their impairment in Osteogenesis imperfecta (OI) leads to a continuous cycle of weakened muscles compromising bone fragility. Understanding the relationship between skeletal muscle weakness and bone pathogenesis is crucial for developing therapeutic targets for OI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Chenyi Shao, Yi Liu, Jiaci Li, Ziyun Liu, Yuxia Zhao, Yaqing Jing, Zhe Lv, Ting Fu, Zihan Wang, Guang Li
Summary: Osteogenesis imperfecta (OI), a congenital bone dysplasia, is mainly caused by defective production or assembly of type I collagen. Studies have found that increased osteoclasts and excessive bone resorption exist in collagen-related OI, which is associated with inflammation. Transcriptomic analysis of bone marrow cells from OI mouse models revealed dysregulated genes and pathways related to interferon response, IL17 signaling, tumor necrosis factor signaling, and osteoclast differentiation. These findings contribute to understanding the mechanism of enhanced bone absorption in OI and provide evidence for potential anti-inflammatory therapies.
Article
Multidisciplinary Sciences
Joohyun Lim, Caressa Lietman, Matthew W. Grol, Alexis Castellon, Brian Dawson, Mary Adeyeye, Jyoti Rai, MaryAnn Weis, Douglas R. Keene, Ronen Schweitzer, Dongsu Park, David R. Eyre, Deborah Krakow, Brendan H. Lee
Summary: This study reveals that defects in Fkbp10 in tendons and ligaments can cause joint dysfunction in osteogenesis imperfecta, involving ectopic chondrogenesis and dysregulated Hedgehog signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medical Laboratory Technology
Se Jin Park, Ju Young Kim, Hye-Jeong Ahn, Haing-Woon Baik, Ju Hyung Kang
Summary: This study investigated the clinical and genetic manifestations in a 7-year-old boy with Osteogenesis imperfecta (OI) and his family members, finding that the OI-related genetic mutation in the patient was inherited from his mother while the GS-related genetic mutations were inherited from both parents. It is the first study to identify compound heterozygous variants in the SLC12A3 gene and a novel mutation in the COL1A1 gene in patients with OI and GS, highlighting the importance of genetic analysis in accurately diagnosing these conditions.
CLINICA CHIMICA ACTA
(2021)
Article
Medicine, Research & Experimental
Luyao Wang, Yuanyuan Yu, Shuaijian Ni, Dijie Li, Jin Liu, Duoli Xie, Hang Yin Chu, Qing Ren, Chuanxin Zhong, Ning Zhang, Nanxi Li, Meiheng Sun, Zong-Kang Zhang, Zhenjian Zhuo, Huarui Zhang, Shu Zhang, Mei Li, Weibo Xia, Zhenlin Zhang, Lin Chen, Peng Shang, Xiaohua Pan, Aiping Lu, Bao-Ting Zhang, Ge Zhang
Summary: The sclerostin loop3-specific aptamer Apc001PE has been shown to promote bone formation without increasing cardiovascular risk in osteogenesis imperfecta (OI) mice, as granted orphan drug designation by US-FDA in 2019.
Article
Endocrinology & Metabolism
Lucinda R. Lee, Aimee E. Holman, Xiaoying Li, Emily R. Vasiljevski, Alexandra K. O'Donohue, Tegan L. Cheng, David G. Little, Aaron Schindeler, Andrew Biggin, Craig F. Munns
Summary: This preclinical study investigated the effects of human growth hormone (hGH) and zoledronic acid (ZA) on bone quality in mice with osteogenesis imperfecta (OI). The results showed that hGH alone increased bone length in wild-type mice, while the combination of hGH/ZA increased bone length in both wild-type and OI mice. MicroCT analysis revealed that hGH/ZA treatment increased cortical bone density and thickness. ZA had a greater impact on trabecular bone, but hGH rescued bone turnover. However, these improvements in bone quality did not translate into improvements in mechanical strength.
Article
Endocrinology & Metabolism
Francesca Tonelli, Laura Leoni, Valentina Daponte, Roberta Gioia, Silvia Cotti, Imke A. K. Fiedler, Daria Larianova, Andy Willaert, Paul J. Coucke, Simona Villani, Bjoern Busse, Roberta Besio, Antonio Rossi, P. Eckhard Witten, Antonella Forlino
Summary: This study used zebrafish to investigate the role of TRIC-B in skeletal tissue. The researchers found that the tmem38b gene is expressed at early developmental stages in zebrafish, while tmem38a gene is not. Mutations in tmem38b resulted in under-modified collagen type I and intracellular retention. These findings contribute to our understanding of the importance of TRIC-B in bone cell differentiation.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Catherine L. Omosule, Dominique Joseph, Brooke Weiler, Victoria L. Gremminger, Spencer Silvey, Youngjae Jeong, Ashique Rafique, Pamela Krueger, Sandra Kleiner, Charlotte L. Phillips
Summary: This study investigated the effects of inhibiting activin A, myostatin, or both on the musculoskeletal system in mice with osteogenesis imperfecta. The results showed that the combination of inhibiting activin A and myostatin was the most effective in increasing muscle mass and bone strength.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Pathology
Rachel B. Keller, Dina El Demellawy, Alberto Quaglia, Milton Finegold, Raj P. Kapur
PEDIATRIC AND DEVELOPMENTAL PATHOLOGY
(2015)
Article
Oncology
Rachel B. Keller, Katelyn E. Gagne, G. Naheed Usmani, George K. Asdourian, David A. Williams, Inga Hofmann, Suneet Agarwal
PEDIATRIC BLOOD & CANCER
(2012)
Article
Oncology
Harshabad Singh, Yvonne Y. Li, Liam F. Spurr, Atul B. Shinagare, Ritika Abhyankar, Emma Reilly, Lauren K. Brais, Anwesha Nag, Matthew D. Ducar, Aaron R. Thorner, Geoffrey Shapiro, Rachel B. Keller, Cheta Siletti, Jeffrey W. Clark, Anna F. Farago, Jessica J. Lin, George D. Demetri, Rahul Gujrathi, Matthew H. Kulke, Laura E. MacConaill, Azra H. Ligon, Ewa Sicinska, Matthew L. Meyerson, Jeffrey A. Meyerhardt, Andrew D. Cherniack, Brian M. Wolpin, Kimmie Ng, Marios Giannakis, Jason L. Hornick, James M. Cleary
Summary: RTK fusions in colorectal cancer are rare but enrich in right-sided and MMR-D colorectal cancers. They occur in RAS and BRAF wild-type tumors, providing an important therapeutic target for MSS colorectal cancer.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Harry Klein, Tali Mazor, Ethan Siegel, Pavel Trukhanov, Andrea Ovalle, Catherine Del Vecchio Fitz, Zachary Zwiesler, Priti Kumari, Bernd Van Der Veen, Eric Marriott, Jason Hansel, Joyce Yu, Adem Albayrak, Susan Barry, Rachel B. Keller, Laura E. MacConaill, Neal Lindeman, Bruce E. Johnson, Barrett J. Rollins, Khanh T. Do, Brian Beardslee, Geoffrey Shapiro, Suzanne Hector-Barry, John Methot, Lynette Sholl, James Lindsay, Michael J. Hassett, Ethan Cerami
Summary: This article introduces an open-source platform called MatchMiner, which computationally matches genomically profiled cancer patients to precision medicine trials, accelerating the trial enrollment process. It provides data to demonstrate the impact of MatchMiner on trial consents.
NPJ PRECISION ONCOLOGY
(2022)
Meeting Abstract
Oncology
Harshabad Singh, Rachel B. Keller, Kevin S. Kapner, Julien Dilly, Srivatsan Raghavan, Chen Yuan, Eizabeth Cohen, Michael Tolstorukov, Emma Hill, Elizabeth Andrews, Lauren K. Brais, Annacarolina Da Silva, Kimberly Perez, Douglas A. Rubinson, Benjamin L. Schlechter, Michael H. Rosenthal, Jason L. Hornick, Valentina Nardi, Yvonne Li, Hersh Gupta, Andrew Cherniack, Mathew L. Meyerson, James M. Cleary, Jonathan A. Nowak, Brian M. Wolpin, Andrew A. Aguirre
Article
Genetics & Heredity
Thao T. Tran, Rachel B. Keller, Brecht Guillemyn, Melanie Pepin, Jane E. Corteville, Samir Khatib, Mohammad-Sadegh Fallah, Sirous Zeinali, Fransiska Malfait, Sofie Symoens, Paul Coucke, Peter Witters, Elena Levtchenko, Hamideh Bagherian, Deborah A. Nickerson, Michael J. Bamshad, Jessica X. Chong, Peter H. Byers
Summary: The genetic disorder osteogenesis imperfecta is characterized by genetic heterogeneity, with most cases caused by variants in COL1A1 or COL1A2 genes. Recent studies have linked different variants in the MESD gene to the progressively deforming phenotype associated with the disorder, highlighting the crucial role of MESD in WNT signaling for bone formation.
HUMAN GENETICS AND GENOMICS ADVANCES
(2021)
Meeting Abstract
Oncology
Tali Mazor, Rachel B. Keller, Priti Kumai, James Lindsay, Eric Marriott, Andrea Ovalle, Ethan Siegel, Joyce Yu, Michael Hassett, Ethan Cerami
Meeting Abstract
Oncology
Rachel B. Keller, Tali Mazor, Marios Giannakis, Jonathan Nowak, Lynette Sholl, Andrew Aguirre, Adam Bass, Nilay Sethi, Ankur Nagaraja, Lauren Brais, Emma Reilly, Ethan Cerami, Brian Wolpin
MOLECULAR CANCER THERAPEUTICS
(2019)
Meeting Abstract
Oncology
Tali Mazor, Rachel B. Keller, Priti Kumari, James Lindsay, Eric Marriott, Andrea Ovalle, Ethan Siegel, Elizabeth H. Williams, Joyce Yu, Michael Hassett, Ethan Cerami
MOLECULAR CANCER THERAPEUTICS
(2019)
Article
Medicine, Research & Experimental
Graham M. Strub, Andrew L. Kirsh, Mark E. Whipple, Winston P. Kuo, Rachel B. Keller, Raj P. Kapur, Mark W. Majesky, Jonathan A. Perkins
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)