A5056722980- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiovascular Disease and Adiposity
- Prenatal Screening and Diagnostics
- Immune cells in cancer
- Adipose Tissue and Metabolism
- Cardiovascular Effects of Exercise
- Alzheimer's disease research and treatments
- Pancreatic function and diabetes
- Genetics and Neurodevelopmental Disorders
- Nuclear Structure and Function
- Cytokine Signaling Pathways and Interactions
- Single-cell and spatial transcriptomics
- Neurogenetic and Muscular Disorders Research
- Adenosine and Purinergic Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Neurological diseases and metabolism
- Pluripotent Stem Cells Research
- interferon and immune responses
- Endoplasmic Reticulum Stress and Disease
- Genetic Syndromes and Imprinting
- Systemic Lupus Erythematosus Research
- Epigenetics and DNA Methylation
- Complement system in diseases
Boston Children's Hospital
2018-2025
Boston Children's Museum
2025
Harvard University
2014-2024
Broad Institute
2014-2024
Harvard Stem Cell Institute
2024
Massachusetts Institute of Technology
2018
Howard Hughes Medical Institute
2018
Dana-Farber Cancer Institute
2012-2014
University of Pennsylvania
1995
Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, understand the unique molecular properties that may sensitize ETNs ALS, we performed RNA sequencing 79,169 single nuclei from cortices patients and controls. In both unaffected individuals, found significantly higher...
While a mutation in C9ORF72 is the most common genetic contributor to amyotrophic lateral sclerosis (ALS), much remains be learned concerning function of protein normally encoded at this locus. To elaborate further on functions for C9ORF72, we used quantitative mass spectrometry-based proteomics identify interacting proteins motor neurons and found that its long isoform complexes with stabilizes SMCR8, which enables interaction WDR41. study organismal cellular tripartite complex, generated...
A mutation in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Patients with ALS or FTD often develop autoimmunity inflammation that precedes coincides onset neurological symptoms, but underlying mechanisms are poorly understood. Here, we knocked out murine C9orf72 seven hematopoietic progenitor compartments by conditional mutagenesis found myeloid lineage prevents splenomegaly, loss tolerance, premature mortality. Furthermore,...
Abstract Background: Although immune checkpoint therapy targeting PD-1/PD-L1 can induce durable responses in cancer patients, it is also associated with epitope spreading and adverse events that limit treatment. Epitope may occur the germinal center (GC), where T follicular helper (TFH) regulatory (TFR) cells interact B to generate humoral immunity. Despite high expression of PD-1 by TFH TFR cells, function its ligand PD-L1 GC remains unknown. Methods: We characterized stromal cell...
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by progressive loss of motor function. The eponymous spinal sclerosis observed at autopsy the result degeneration extratelencephalic neurons, Betz cells (ETNs, Cortico-Spinal Motor Neuron). It remains unclear why this neuronal subtype selectively affected. To understand unique molecular properties that sensitise these to ALS, we performed RNA sequencing 79,169 single nuclei from cortices patients and...
Since the identification of DNA methylation as a master regulator genomic imprinting more than 20 years ago, it has been only known mammalian germline mark. However, recent studies have identified several imprinted genes capable maintaining paternal allele-specific expression in absence oocyte methylation. Here, researchers find 76 that are paternally expressed (maternal alleles repressed) due to DNA-methylation-independent mechanism. These involved and essential for embryonic development. A...
Summary Mounting evidence implicated the classical complement pathway (CP) in normal brain development, and pathogenesis of neuropsychiatric neurodegenerative diseases. However source regulation remain unclear. Using MERFISH, a spatial transcriptomic method with single-cell resolution, we established developmental atlas system. We showed that synthesizes essential building blocks system locally remarkable cellular heterogeneity. provided transcriptional supporting presence alternative (AP),...