Review
Immunology
Jun Wang, Miriam Erlacher, Juncal Fernandez-Orth
Summary: Under inflammatory conditions, steady-state hematopoiesis switches to emergency myelopoiesis, leading to different forms of cell death and other changes in the hematopoietic system, ultimately causing loss of hematopoiesis function. In individuals with inherited bone marrow failure syndromes or immune-mediated aplastic anemia, chronic inflammatory signals may aggravate disease progression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Christine J. Chang, Luzmariel Medina Sanchez, Aditya Vageesh, Alexandra J. Popkov, Adithya Chandrasekaran, Bethany B. Moore, Jason B. Weinberg
Summary: Long-term persistence of DNA viruses in the infected host is crucial for their life cycle. The nature of adenovirus persistence following acute infection is not fully understood. In this study, we found that mouse adenovirus type 1 (MAV-1) persists for a prolonged period in multiple organs of infected mice without ongoing replication. Furthermore, MAV-1 persistence exacerbated graft-versus-host disease-like inflammation following allogeneic bone marrow transplantation, even in the absence of virus reactivation. These findings suggest that adenovirus persistence can have consequences and influence host responses to unrelated challenges.
JOURNAL OF VIROLOGY
(2022)
Article
Medicine, Research & Experimental
Yiouli P. Ktena, Michael A. Koldobskiy, Michael I. Barbato, Han-Hsuan Fu, Leo Luznik, Nicolas J. Llosa, Azeb Haile, Orly R. Klein, Chen Liu, Christopher J. Gamper, Kenneth R. Cooke
Summary: DNA methyltransferase 3a (DNMT3a) plays a critical role in regulating T cell alloreactivity by controlling T cell signaling and differentiation pathways, thereby modulating T cell tolerance.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Hematology
Hannah Kinoshita, Mamatha Mandava, Mariah Jensen-Wachspress, Haili Lang, Elisabeth Joy, Jay Tanna, Chase D. McCann, Samuel O'Brien, Sianna Burnett, Abeer Shibli, Fahmida Hoq, Monica Bhatia, Patrick J. Hanley, Blachy Davila Saldana, Kris M. Mahadeo, Catherine M. Bollard, Michael D. Keller, Allistair Abraham
Summary: Hematopoietic stem cell transplantation (HSCT) is increasingly used to treat sickle cell disease (SCD). However, this treatment increases the risk of viral infection. This study explores the use of virus-specific T-cell (VST) therapies after HSCT to prevent or treat viral infections in SCD patients.
Editorial Material
Hematology
Mark Leick, Yi-Bin Chen
Summary: In this study, McCurdy et al compare immune restoration after haploidentical and matched donor HCT, and find that high-dose PTCy-based GVHD prophylaxis is effective in immune recovery.
Article
Neurosciences
Elna Dickson, Amoolya Sai Dwijesha, Natalie Andersson, Sofia Lundh, Maria Bjorkqvist, Asa Petersen, Rana Soylu-Kucharz
Summary: This study investigated the transcriptional changes caused by hypothalamic expression of huntingtin (HTT) gene in Huntington's disease (HD). The results showed that both wild-type HTT (wtHTT) and mutant HTT (mHTT) overexpression altered the hypothalamic transcriptome profile, with mHTT specifically affecting neuroendocrine circuits. However, the ubiquitous expression of full-length mHTT in the BACHD mouse model moderately affected the transcriptomic profile.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Sandra Pinho, Qiaozhi Wei, Maria Maryanovich, Dachuan Zhang, Juan Carlos Balandran, Halley Pierce, Fumio Nakahara, Anna Di Staulo, Boris A. Bartholdy, Jianing Xus, Daniel K. Borger, Amit Verma, Paul S. Frenette
Summary: VCAM1 not only exists on healthy HSCs, but is also upregulated on leukaemic stem cells (LSCs), where it plays a 'don't-eat-me' role through interaction with MHC-I presentation, ensuring the integrity of HSCs when entering the bone marrow. The 'don't-eat-me' activity of VCAM1 is regulated by beta 2-microglobulin MHC presentation on HSCs and paired Ig-like receptor-B (PIR-B) on phagocytes. Additionally, VCAM1 is upregulated in cancer cells, providing an avenue for cancer cells to escape immune detection.
NATURE CELL BIOLOGY
(2022)
Review
Immunology
Xiaofeng Zhou, Bethany B. Moore
Summary: Pulmonary infections are a major concern for hematopoietic cell transplantation recipients, with mouse models playing a key role in understanding the impacts of these infections. Studies have shown that post-transplant infectious complications adversely affect innate immunity, and previous infections may contribute to noninfectious pulmonary issues post-HCT.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Shota Shimizu, Shinri Sato, Hiroko Taniguchi, Eisuke Shimizu, Jingliang He, Shunsuke Hayashi, Kazuno Negishi, Yoko Ogawa, Shigeto Shimmura
Summary: The study observed the dynamics of inflammatory cells in the cornea of chronic GVHD model mice, discovering that neovascularization occurred in all eyes at 1 week after BMT but almost all vessels disappeared at 2 weeks after BMT. Additionally, infiltration of globular cells and tortuosity and branching of nerves were found in both cGVHD mice and human cGVHD patients.
Article
Biochemistry & Molecular Biology
Roberto Speziale, Camilla Montesano, Giulia Di Pietro, Daniel Oscar Cicero, Vincenzo Summa, Edith Monteagudo, Laura Orsatti
Summary: Huntington's disease (HD) is a genetic condition caused by the expansion of a specific sequence in the huntingtin gene. There is a lack of effective treatments for HD, highlighting the need for reliable mouse models for preclinical studies. This study utilized a urinary liquid chromatography-high-resolution mass spectrometry analysis to identify metabolic changes in different HD mouse models, aiming to improve our understanding of the disease and identify potential biomarkers.
Review
Immunology
Motoko Koyama, Geoffrey R. Hill
Summary: Allogeneic stem cell transplantation is an effective therapy for hematopoietic malignancies, relying on donor T cells and NK cells for the graft-versus-leukemia effect. However, graft-versus-host disease remains a major complication, highlighting the importance of understanding alloantigen presentation to separate beneficial effects from detrimental ones. Mouse models and tools play a key role in quantifying alloantigen presentation post-alloSCT.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Kerstin Voelkl, Elena Katharina Schulz-Trieglaff, Ruediger Klein, Irina Dudanova
Summary: This study investigates histological changes in cortical interneurons in mouse models of Huntington's disease. The findings suggest differential molecular changes in different interneuron types, with a selective reduction in SST and VIP cells but no change in PV cells. The study also observes a reduction in cell body size for all three interneuron populations and progressive accumulation of mutant Huntingtin inclusion bodies, which occurs faster in SST and VIP cells compared to PV cells.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Immunology
Nicholas J. Hess, Matthew E. Brown, Christian M. Capitini
Summary: GVHD is a common cause of non-relapse mortality following HSCT, and research faces challenges in translating findings from murine studies to human biology. Utilizing xenogeneic HSCT models to study human T cell responses allows for the assessment of key factors in GVHD pathogenesis before clinical trials.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Genetics & Heredity
Karolina Pierzynowska, Magdalena Podlacha, Dorota Luszczek, Estera Rintz, Lidia Gaffke, Zuzanna Szczudlo, Marta Tomczyk, Ryszard T. Smolenski, Grzegorz Wegrzyn
Summary: This study identified abnormal hair morphology as a potential simple marker for testing therapeutic effects or disease progression in widely used HD mouse models R6/1 and R6/2.
Article
Clinical Neurology
Antonio Uccelli, Alice Laroni, Rehiana Ali, Mario Alberto Battaglia, Morten Blinkenberg, Lou Brundin, Michel Clanet, Oscar Fernandez, James Marriot, Paolo Muraro, Seyed Massood Nabavi, Roberto S. Oliveri, Ernst Radue, Cristina Ramo Tello, Irene Schiavetti, Johann Sellner, Per Soelberg Sorensen, Maria Pia Sormani, Jens Thomas Wuerfel, Mark S. Freedman
Summary: The MESEMS study aimed to evaluate the safety and activity of autologous bone marrow-derived MSCs in patients with active multiple sclerosis. The results showed that MSC treatment did not affect GELs and does not support its use in treating multiple sclerosis.
Review
Clinical Neurology
Joaquim J. Ferreira, Filipe B. Rodrigues, Goncalo S. Duarte, Tiago A. Mestre, Anne-Catherine Bachoud-Levi, Anna Rita Bentivoglio, Jean-Marc Burgunder, Francisco Cardoso, Daniel O. Claassen, G. Bernard Landwehrmeyer, Jaime Kulisevsky, Melissa J. Nirenberg, Anne Rosser, Jan Roth, Klaus Seppi, Jaroslaw Slawek, Erin Furr-Stimming, Sarah J. Tabrizi, Francis O. Walker, Wim Vandenberghe, Joao Costa, Cristina Sampaio
Summary: The management of Huntington's disease (HD) is challenging and mainly consists of off-label treatments. A task force was commissioned to review available therapies for HD gene expansion carriers. Limited data supports the use of VMAT2 inhibitors for specific motor symptoms.
MOVEMENT DISORDERS
(2022)
Article
Psychology, Clinical
Akshay Nair, Ritwik K. Niyogi, Fei Shang, Sarah J. Tabrizi, Geraint Rees, Robb B. Rutledge
Summary: This study provides new insights into understanding and explaining apathy, a disabling neuropsychiatric symptom, by investigating the relationship between the opportunity cost of time (OCT), self-initiation, and apathy. The findings suggest that OCT is an important variable for determining free-operant action initiation and understanding apathy.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Neuroimaging
Paul Zeun, Peter McColgan, Thijs Dhollander, Sarah Gregory, Eileanoir B. Johnson, Marina Papoutsi, Akshay Nair, Rachael Scahill, Geraint Rees, Sarah J. Tabrizi
Summary: The study found that cortico-basal ganglia white matter loss begins in premanifest Huntington's disease (preHD) approximately 11 years before symptom onset. The most vulnerable white matter tracts are those connecting the striatum and thalamus. Additionally, there is a significant correlation between fiber density and cross section in these tracts and the Unified Huntington's disease rating scale (UHDRS) total motor score (TMS).
NEUROIMAGE-CLINICAL
(2022)
Letter
Clinical Neurology
Ramita Dewan, Zane Jaunmuktane, Monica Emili Garcia-Segura, Catherine Strand, Edward Wild, Joaquin Villar, Clifton L. Dalgard, Sarah J. Tabrizi, Bryan J. Traynor, Christos Proukakis
MOVEMENT DISORDERS
(2022)
Article
Multidisciplinary Sciences
Austin Chou, Abel Torres-Espin, Nikos Kyritsis, J. Russell Huie, Sarah Khatry, Jeremy Funk, Jennifer Hay, Andrew Lofgreen, Rajiv Shah, Chandler McCann, Lisa U. Pascual, Edilberto Amorim, Philip R. Weinstein, Geoffrey T. Manley, Sanjay S. Dhall, Jonathan Z. Pan, Jacqueline C. Bresnahan, Michael S. Beattie, William D. Whetstone, Adam R. Ferguson
Summary: Artificial intelligence and machine learning have the potential to transform biomedicine by optimizing predictive models and enhancing understanding of disease biology. Automated machine learning, in particular, can democratize AI by reducing the need for human input and expertise. However, successful application of AI and machine learning in biomedicine requires reproducible clinical and biological inferences, which is challenging for rare disorders with small patient cohorts. A model-agnostic framework that incorporates explainable and reproducible AI strategies is proposed to enhance AutoML and facilitate clinical interpretation and integration of expert knowledge.
Article
Computer Science, Information Systems
Alan D. Kaplan, Qi Cheng, K. Aditya Mohan, Lindsay D. Nelson, Sonia Jain, Harvey Levin, Abel Torres-Espin, Austin Chou, J. Russell Huie, Adam R. Ferguson, Michael McCrea, Joseph Giacino, Shivshankar Sundaram, Amy J. Markowitz, Geoffrey T. Manley
Summary: In this study, a method for modeling heterogeneous data types relevant to TBI was developed to depict the nuanced differences in TBI patients' recovery. The model was trained on various data types and used to infer outcomes based on input data. Additionally, the performance of a likelihood scoring technique for evaluating the risk of prognosis extrapolation was quantified.
IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
(2022)
Article
Neurosciences
Jenny Lange, Olivia Gillham, Michael Flower, Heather Ging, Simon Eaton, Sneha Kapadia, Andreas Neueder, Michael R. Duchen, Patrizia Ferretti, Sarah J. Tabrizi
Summary: Huntington's Disease is a neurodegenerative disease caused by a genetic mutation. Astrocyte dysfunction, specifically changes in gene expression and metabolic activity, plays a role in the pathogenesis of the disease. Additionally, all Huntington's Disease astrocytes exhibit increased DNA damage and a DNA damage response, suggesting a potential mechanism for their dysfunction.
PROGRESS IN NEUROBIOLOGY
(2023)
Editorial Material
Neurosciences
Mena Farag, Desiree M. Salanio, Cara Hearst, Daniela Rae, Sarah J. Tabrizi
Summary: Advance care planning (ACP) is a beneficial tool that allows adult patients to express and formalize their beliefs, preferences, and wishes regarding future medical care. For Huntington's disease (HD) patients, early consideration of ACP is crucial due to challenges in determining decision-making capacity in the later stages of the disease. ACP empowers patients and provides reassurance to clinicians and surrogate decision makers by ensuring that medical management aligns with the patient's expressed wishes. Regular follow-up is necessary to maintain consistency in decisions and wishes. We outline the framework of our dedicated ACP clinic within the HD service, emphasizing the importance of patient-centered and personalized care plans that reflect the patient's goals, preferences, and values.
JOURNAL OF HUNTINGTONS DISEASE
(2023)
Article
Clinical Neurology
Andreas-Antonios Roussakis, Marta Gennaro, Mark Forrest Gordon, Ralf Reilmann, Beth Borowsky, Gail Rynkowski, Nicholas P. Lao-Kaim, Zoe Papoutsou, Juha-Matti Savola, Michael R. Hayden, David R. Owen, Nicola Kalk, Anne Lingford-Hughes, Roger N. Gunn, Graham Searle, Sarah J. Tabrizi, Paola Piccini
Summary: This longitudinal study demonstrates that the treatment of laquinimod in Huntington's disease does not affect regional microglia activation. Microglia activation is believed to be related to inflammation in the central nervous system and the progression of Huntington's disease. However, laquinimod is capable of regulating microglia. The study also shows that C-11-PBR28 PET-CT imaging can be used to assess regional gliosis and the effects of laquinimod treatment.
BRAIN COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Sangeerthana Rajagopal, Jasmine Donaldson, Michael Flower, Davina J. Hensman Moss, Sarah J. Tabrizi
Summary: Repeat expansion disorders (REDs) are monogenic diseases caused by repetitive DNA sequences expanding beyond a pathogenic threshold. The length of the repeat sequence is a major determinant of age at onset and disease progression. Phenotypic variability in REDs is influenced by factors such as the gene involved, the location of the repeat sequence, and the presence of interruptions. DNA repair pathways have been identified as potential modifiers of RED phenotypes, offering potential targets for disease-modifying therapies.
EMERGING TOPICS IN LIFE SCIENCES
(2023)
Article
Clinical Neurology
Chin-Fu Liu, Laurent Younes, Xiao J. Tong, Jared T. Hinkle, Maggie Wang, Sanika Phatak, Xin Xu, Xuan Bu, Vivian Looi, Jee Bang, Sarah J. Tabrizi, Rachael Scahill, Jane S. Paulsen, Nellie Georgiou-Karistianis, Andreia Faria, Michael Miller, J. Tilak Ratnanather, Christopher A. Ross
Summary: Huntington's disease is caused by a CAG repeat expansion in the Huntingtin gene, resulting in increased polyglutamine in the Huntingtin protein. This study analyzed three longitudinal datasets and found significant selective atrophy in multiple regions, supporting the hypothesis of circuit-based spread of pathology in Huntington's disease.
BRAIN COMMUNICATIONS
(2023)
Meeting Abstract
Clinical Neurology
Lauren M. Byrne, Jordan L. Schultz, Sophie Field, Kate Fayer, Yara Hassan, Filipe B. Rodrigues, Ellen van der Plas, Douglas Langbehn, Sarah J. Tabrizi, Peggy C. Nopoulos, Edward J. Wild
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Annabelle Coleman, Mackenzie T. Langan, Gaurav Verma, Harry Knights, Rachelle Dar Santos, Allison Coleman, Aaron Sturrock, Blair R. Leavitt, Sarah J. Tabrizi, Rachael I. Scahill, Nicola Z. Hobbs
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Jasmine Donaldson, Joseph Hamilton, Jessica Olive, Robert Goold, Sarah J. Tabrizi
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Meeting Abstract
Clinical Neurology
Ross Ferguson, Michael Flower, Sarah J. Tabrizi
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)