Editorial Material
Medicine, Research & Experimental
Jung-Hyun Kim, Liping Li, Linda M. S. Resar
Summary: The study revealed a drug-targetable signaling pathway in B-ALL, providing new therapeutic strategies for leukemia patients with or without Down syndrome.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
Ines H. Kaltheuner, Kanchan Anand, Jonas Moecking, Robert Duester, Jinhua Wang, Nathanael S. Gray, Matthias Geyer
Summary: Abemaciclib, a CDK inhibitor for breast cancer treatment, also targets HIPKs and DYRK1A. HIPKs play a role in signal pathway regulation, and DYRK1A is inhibited by Abemaciclib in vitro to a similar extent as Cdk4/Cdk6.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Liat Stoler-Barak, Ethan Harris, Ayelet Peres, Hadas Hezroni, Mirela Kuka, Pietro Di Lucia, Amalie Grenov, Neta Gurwicz, Meital Kupervaser, Bon Ham Yip, Matteo Iannacone, Gur Yaari, John D. Crispino, Ziv Shulman
Summary: The protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination by regulating class switch recombination (CSR). It plays a crucial role in B cell immune responses, including attenuating B cell proliferation and promoting the production of pathogen-eliminating antibodies.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Kunal Kumar, Chalada Suebsuwong, Peng Wang, Adolfo Garcia-Ocana, Andrew F. Stewart, Robert J. DeVita
Summary: The research focuses on regenerating functional insulin-producing human beta cells in people with diabetes using DYRK1A inhibitor drugs. These inhibitors have been found to induce beta-cell proliferation and synergize with other classes of drugs to enhance the effect.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Katelyn Millette, Keith Rodriguez, Xia Sheng, Stacey D. Finley, Senta Georgia
Summary: This study establishes a novel pseudopregnancy model and demonstrates that pseudopregnancy promotes beta cell proliferation. Estrogen, progesterone, and placental lactogen induce beta cell replication in the pseudopregnancy model. Similar effects were observed in vitro experiments.
Article
Hematology
Yanchuan Li, Xiaoping Xie, Zuliang Jie, Lele Zhu, Jin-Young Yang, Chun-Jung Ko, Tianxiao Gao, Antrix Jain, Sung Yun Jung, Natalia Baran, Marina Y. Konopleva, Xuhong Cheng, Shao-Cong Sun
Summary: DYRK1a is identified as a critical mediator in the BAFF signaling pathway, playing a key role in B-cell survival and contributing to the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL).
Article
Oncology
Shichuan Tan, Juan Zhao, Pin Wang
Summary: Polo-like kinases (PLKs) are serine-threonine kinases that regulate cellular processes, including in cancer. PLK2 expression is lower in GBM tumor tissue compared to normal brains and high expression is correlated with poor prognosis. In this study, it was shown that DYRK1A interacts with and phosphorylates PLK2, increasing its stability and kinase activity. DYRK1A-mediated phosphorylation of PLK2 contributes to the proliferation, migration, and invasion of GBM cells and enhances the inhibitory effects of PLK2 on GBM malignancy. These findings suggest that PLK2 may play a crucial role in GBM pathogenesis in a DYRK1A-dependent manner, and PLK2 Ser358 could be a therapeutic target for GBM.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Article
Cell Biology
Agata Barzowska, Barbara Pucelik, Katarzyna Pustelny, Alex Matsuda, Alicja Martyniak, Jacek Stepniewski, Anna Maksymiuk, Maciej Dawidowski, Ulli Rothweiler, Jozef Dulak, Grzegorz Dubin, Anna Czarna
Summary: This study demonstrates the efficacy of a set of small molecule inhibitors of DYRK1A kinase in promoting beta-cell proliferation, enhancing long-term insulin secretion, and balancing glucagon level in human islets. The compounds show significantly more pronounced effects compared to harmine and hold considerable promise for regenerative medicine in the treatment of T1DM and T2DM.
Article
Neurosciences
Isidora Paredes, Jose Ricardo Vieira, Bhavin Shah, Carla F. Ramunno, Julia Dyckow, Heike Adler, Melanie Richter, Geza Schermann, Evangelia Giannakouri, Lucas Schirmer, Hellmut G. Augustin, Carmen Ruiz de Almodovar
Summary: Bidirectional crosstalk between neural and vascular compartments plays a critical role in oligodendrocyte precursor cell specification, with neural progenitor cells expressing angiopoietin-1 and endothelial cells producing transforming growth factor beta 1 in response. This collaboration demonstrates the complex relationship between NPCs and the vasculature in regulating oligodendrogenesis.
NATURE NEUROSCIENCE
(2021)
Article
Nanoscience & Nanotechnology
Lijie Mao, Long Bai, Xinqing Wang, Xiaolei Chen, Dong Zhang, Fangping Chen, Changsheng Liu
Summary: The study explored the effects of different surface charges on BMSCs and RAW264.7 cell osteogenesis and osteoimmunology using piezoelectric BaTiO3/β-TCP (BTCP) ceramics. Polarized BTCP with negative surface charge (BTCP-) promoted protein adsorption, BMSC extracellular Ca2+ influx, attachment, spreading, migration, and osteogenic differentiation of BMSCs. Conversely, polarized BTCP ceramics with positive surface charge (BTCP+) significantly inhibited M1 polarization of macrophages, impacting the expression of M1 marker in macrophages and changing secretion of proinflammatory cytokines, thus enhancing osteogenic differentiation of BMSCs.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Oncology
Amina Jamal Laham, Raafat El-Awady, Jean-Jacques Lebrun, Maha Saber Ayad
Summary: DYRK1A expression is upregulated in colorectal cancer and associated with poor prognosis.
Article
Biochemistry & Molecular Biology
Shuang Li, Ge Tao
Summary: A cell's roles extend beyond its life span, even after its demise. Regulated cell death (RCD) is a crucial topic in biomedical studies, primarily used to eliminate stressed or damaged cells. Recent research has uncovered new roles of RCD, including tissue development coordination and compensatory proliferation during tissue repair.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Endocrinology & Metabolism
Sharon Baumel-Alterzon, Liora S. Katz, Gabriel Brill, Clairete Jean-Pierre, Yansui Li, Isabelle Tse, Shyam Biswal, Adolfo Garcia-Ocana, Donald K. Scott
Summary: By manipulating Nrf2 levels, researchers have discovered the importance of managing reactive oxygen species in regulating beta-cell mass, highlighting Nrf2 as an exciting therapeutic target for expanding and protecting beta-cell mass in diabetes.
Review
Immunology
Chiara Capelli, Carolina Cuofano, Chiara Pavoni, Simona Frigerio, Daniela Lisini, Sara Nava, Michele Quaroni, Valentina Colombo, Francesco Galli, Svetlana Bezukladova, Paola Panina-Bordignon, Giuseppe Gaipa, Patrizia Comoli, Giulio Cossu, Gianvito Martino, Andrea Biondi, Martino Introna, Josee Golay
Summary: Advanced Therapy Medicinal Products (ATMPs) based on somatic cells expanded in vitro, with or without genetic modification, is a rapidly growing area of drug development. Potency assays are crucial for assessing the quality of ATMPs, and biomarkers may serve as substitutes for complex functional potency tests in predicting the efficacy of these cell-based drugs in vivo.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jacob G. Kallenbach, Margaret A. T. Freeberg, David Abplanalp, Rahul G. Alenchery, Raquel E. Ajalik, Samantha Muscat, Jacquelyn A. Myers, John M. Ashton, Alayna Loiselle, Mark R. Buckley, Andre J. van Wijnen, Hani A. Awad
Summary: This study investigates the molecular mechanisms of tendon healing using the MRL mouse model. The results show that injured MRL tendons have reduced fibrotic adhesions and cellular proliferation, with accelerated improvements in biomechanical properties. Gene expression analysis reveals differences in pathways related to fibrosis, immune system signaling, and cell cycle regulation between MRL and C57 mice. These findings provide important insights for improving tendon healing.
SCIENTIFIC REPORTS
(2022)
Article
Surgery
Wilson Alobuia, Justin Annes, Electron Kebebew
Article
Multidisciplinary Sciences
Timothy M. Horton, Vandana Sundaram, Christine Hye-Jin Lee, Kathleen Hornbacker, Aidan Van Vleck, Kaisha N. Benjamin, Allison Zemek, Teri A. Longacre, Pamela L. Kunz, Justin P. Annes
SCIENTIFIC REPORTS
(2020)
Article
Surgery
Wilson M. Alobuia, Sabrine Ammar, Monica Tyagi, Chandrayee Ghosh, Viswanath Gunda, Justin P. Annes, Electron Kebebew
Summary: Genetic testing for pheochromocytoma and paraganglioma susceptibility genes is more likely to be positive in patients with a positive family history, aged <= 47 years, and tumor size <= 2.9 cm. Patients meeting all three criteria have a 100% probability of testing positive.
Article
Cardiac & Cardiovascular Systems
Brandon A. Guenthart, Winston Trope, Worasak Keeyapaj, Julianna J. Weiel, Amanda Edmonson, John W. MacArthur, Justin P. Annes, Y. Joseph Woo, Natalie S. Lui
Summary: Intracardiac paragangliomas, commonly found in the left atrium, are often infiltrative and densely adherent to surrounding structures. Due to their rarity, only scattered reports exist in the literature and standardized perioperative and surgical management is not well established.
GENERAL THORACIC AND CARDIOVASCULAR SURGERY
(2021)
Article
Endocrinology & Metabolism
Rayhan A. Lal, Hannah P. Moeller, Ella A. Thomson, Timothy M. Horton, Sooyeon Lee, Raquel Freeman, Priya Prahalad, Ada S. Y. Poon, Justin P. Annes
Summary: In this study, a novel INS gene mutation (p.T97P) was identified, which disrupts proinsulin folding and processing, leading to the development of MIDY. This mutation induces endoplasmic reticulum stress and impairs insulin secretion.
Article
Endocrinology & Metabolism
Sooyeon Lee, Haixia Xu, Aidan Van Vleck, Alex M. Mawla, Albert Mao Li, Jiangbin Ye, Mark O. Huising, Justin P. Annes
Summary: Mitochondrial dysfunction plays a central role in type 2 diabetes, and the pathogenic mechanisms in pancreatic beta-cells are not fully understood. In this study, using samples from diabetic individuals and a mouse model, the authors demonstrate that succinate dehydrogenase (SDH) deficiency drives mitochondrial dysfunction in beta-cell failure and insulinopenic diabetes. SDH deficiency impairs glucose-induced respiratory oxidative phosphorylation and compromises glucose-stimulated ATP production, insulin secretion, and beta-cell growth. The loss of SDH causes excess succinate accumulation, which activates metabolic anabolism and lipid synthesis. This study suggests that SDH deficiency is a contributing mechanism to progressive beta-cell failure in diabetes and identifies mTOR complex 1 inhibition as a potential strategy for mitigation.
Article
Cell Biology
Neali Armstrong, Claire M. Storey, Sarah E. Noll, Katherine Margulis, Myat Han Soe, Haixia Xu, Benjamin Yeh, Lauren Fishbein, Electron Kebebew, Brooke E. Howitt, Richard N. Zare, Julien Sage, Justin P. Annes
Summary: Inherited pathogenic succinate dehydrogenase (SDHx) gene mutations cause hereditary pheochromocytoma and paraganglioma tumor syndrome. However, accumulation of succinate and inhibition of 2-oxoglutarate-dependent dioxygenase are insufficient for tumor formation in pheochromocytoma, additional growth-regulatory pathway activation is required.
Editorial Material
Peripheral Vascular Disease
Christina Bradshaw, Aya Abounasr, Ryan L. Brunsing, Chia-Sui Kao, Risheen Reejhsinghani, Justin P. Annes, Benjamin I. Chung, Frederick Mihm, Vivek Bhalla
Article
Chemistry, Multidisciplinary
Max L. Wang, Christian F. Chamberlayne, Haixia Xu, Mohammad Mofidfar, Spyridon Baltsavias, Justin P. Annes, Richard N. Zare, Amin Arbabian
Summary: On-demand drug delivery systems combined with wireless implants can control drug release, reducing dosage and side effects. Researchers designed a release system based on a modified electroresponsive polypyrrole nanoparticulate film for negatively charged compounds. They also developed an ultrasonically powered mm-sized implant to electronically control the on-demand drug delivery system in vivo. The feasibility of wireless, controllable drug release was demonstrated through in vitro and in vivo characterization using fluorescein as a model drug.
Proceedings Paper
Computer Science, Information Systems
Max L. Wang, Pyungwoo Yeon, Christian F. Chamberlayne, Mohammad Mofidfar, Haixia Xu, Justin P. Annes, Richard N. Zare, Amin Arbabian
Summary: This study presents an ultrasonically powered implantable potentiostat for programmable drug delivery control. The system is complex, consisting of multiple functional modules for bidirectional communication and drug release. The wireless powered and controlled fluorescein release successfully demonstrates the system's effectiveness.
2021 IEEE BIOMEDICAL CIRCUITS AND SYSTEMS CONFERENCE (IEEE BIOCAS 2021)
(2021)
Article
Biochemical Research Methods
Timothy M. Horton, Benjamin R. Kraemer, Justin P. Annes
Summary: This study explores the targeted drug delivery to pancreatic islet 13 cells, focusing on the unique high Zn2+ concentration in these cells and the integration of Zn2+-binding activity into small molecules for specific accumulation and activity. One challenge is establishing an LC-MS/MS-based method for compound measurement, with limitations such as target compound ionizability and time sensitivity in experimental steps.
Review
Surgery
Rashad Jabarkheel, Arjun Pendharkar, Jonathan L. Lavezo, Justin Annes, Kaniksha Desai, Hannes Vogel, Atman M. Desai
Summary: This article presents a case of metastatic spinal PGL in a patient with pathogenic SDHB mutation, emphasizing the importance of genetic testing and long-term surveillance for these patients.
INTERNATIONAL JOURNAL OF SPINE SURGERY
(2021)
Meeting Abstract
Chemistry, Multidisciplinary
Christian Chamberlayne, Spyridon Baltsavias, Haixia Xu, Amin Arbabian, Justin Annes, Richard Zare
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Biochemistry & Molecular Biology
Timothy M. Horton, Paul A. Allegretti, Sooyeon Lee, Hannah P. Moeller, Mark Smith, Justin P. Annes
CELL CHEMICAL BIOLOGY
(2019)