A5027849979- Epigenetics and DNA Methylation
- Nutrition, Genetics, and Disease
- Genetics and Neurodevelopmental Disorders
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
- RNA Research and Splicing
- Tryptophan and brain disorders
- MicroRNA in disease regulation
- Liver physiology and pathology
- Schizophrenia research and treatment
- RNA and protein synthesis mechanisms
- Single-cell and spatial transcriptomics
- Genomics and Chromatin Dynamics
- Cardiac Health and Mental Health
- Psychosomatic Disorders and Their Treatments
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Pluripotent Stem Cells Research
- T-cell and B-cell Immunology
- Child and Adolescent Psychosocial and Emotional Development
- Health Systems, Economic Evaluations, Quality of Life
- Inflammatory Bowel Disease
- Mental Health and Psychiatry
University of Massachusetts Chan Medical School
2022-2025
Broad Institute
2022-2025
Harvard University
2021-2024
Massachusetts General Hospital
2021-2023
Massachusetts Institute of Technology
2022
University of Kansas Medical Center
2021
Dow University of Health Sciences
2010-2020
University Medical Center Hamburg-Eppendorf
2017-2019
Universität Hamburg
2017-2019
German Center for Neurodegenerative Diseases
2015-2018
The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult obtain in vivo. They readily measured vitro by feeding cells with isotopically labeled amino acids, followed mass spectrometry analyses. In vivo generated from at least two sources: acids the diet, non-labeled degradation pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously a workflow...
In patients with Charcot-Marie-Tooth disease 1A (CMT1A), peripheral nerves display aberrant myelination during postnatal development, followed by slowly progressive demyelination and axonal loss adult life. Here, we show that myelinating Schwann cells in a rat model of CMT1A exhibit developmental defect includes reduced transcription genes required for myelin lipid biosynthesis. Consequently, incorporation into is reduced, leading to an overall distorted stoichiometry proteins lipids...
Altered enteric microorganisms in concert with host genetics shape inflammatory bowel disease (IBD) phenotypes. However, insight is limited to bacteria and fungi. We found that eukaryotic viruses bacteriophages (collectively, the virome), enriched from non-IBD, noninflamed human colon resections, actively elicited atypical anti-inflammatory innate immune programs. Conversely, ulcerative colitis or Crohn's resection viromes provoked inflammation, which was successfully dampened by non-IBD...
Objectives Non-alcoholic fatty liver disease (NAFLD) can persist in the stage of simple hepatic steatosis or progress to steatohepatitis (NASH) with an increased risk for cirrhosis and cancer. We examined mechanisms controlling progression severe NASH order develop future treatment strategies this disease. Design NFATc1 activation regulation was livers from patients NAFLD, cultured primary hepatocytes transgenic mice differential hepatocyte-specific expression transcription factor ( Alb-cre,...
Small RNA molecules play important roles in many biological processes and their dysregulation or dysfunction can cause disease. The current method of choice for genome-wide sRNA expression profiling is deep sequencing. Here we present Oasis 2, which a new main release the web application detection, differential expression, classification small RNAs sequencing data. Compared to its predecessor Oasis, 2 features novel speed-optimized detection module that supports identification any organism...
Abstract Summary: Oasis is a web application that allows for the fast and flexible online analysis of small-RNA-seq (sRNA-seq) data. It was designed end user in lab, providing an easy-to-use frontend including video tutorials, demo data best practice step-by-step guidelines on how to analyze sRNA-seq Oasis’ exclusive selling points are differential expression module multivariate samples, classification robust biomarker detection advanced programming interface supports batch submission jobs....
Background Nephron number is a major determinant of long-term renal function and cardiovascular risk. Observational studies suggest that maternal nutritional metabolic factors during gestation contribute to the high variability nephron endowment. However, underlying molecular mechanisms have been unclear. Methods We used mouse models, including DNA methyltransferase ( Dnmt1, Dnmt3a, Dnmt3b ) knockout mice, optical projection tomography, three-dimensional reconstructions nephrogenic niche,...
Article14 December 2017Open Access Transparent process The landscape of human mutually exclusive splicing Klas Hatje Group Systems Biology Motor Proteins, Department NMR-Based Structural Biology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany Computational German Center Neurodegenerative Diseases, Search more papers by this author Raza-Ur Rahman Molecular Neurobiology, Institute Medical University Clinic Hamburg-Eppendorf, Hamburg, Ramon O Vidal Dominic Simm Theoretical...
NeuroLNC , a previously unknown long ncRNA, regulates neuronal activity by interacting with the neurodegeneration protein TDP-43.
NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials immune-suppressant methotrexate We tested if low-dose used treatment systemic autoimmune disorders would be tolerable and effective people with a feasibility study. Ninety-two participants within 5 years diagnosis were recruited from inpatient outpatient facilities Karachi, Pakistan. They...
Abstract The liver is a vital organ composed of parenchymal, nonparenchymal, and immune cell populations, which are now being mapped at single resolution. Here we present detailed map the cellular composition human through single-nucleus RNA sequencing (snRNA-seq), incorporating insights from 32 healthy samples. dataset contains cells female male donors spanning more than seven decades age. Excluding X Y chromosome, identified ∼500 genes uniquely enriched in liver, ∼600 liver. These tend to...
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of morbidity with limited treatment options. Thus, accurate in vitro systems to test new therapies are indispensable. While recently, human organoid models have emerged assess disease, systematic evaluation their translational potential still missing. Here, we evaluated MASLD, comparatively testing induction three conditions: oleic acid, palmitic and TGF-β1. Through single-cell analyses, find that all induce...
Background and Aims: Fibrosis is the common end point for all forms of chronic liver injury, progression fibrosis leads to development end-stage disease. Activation HSCs their transdifferentiation into myofibroblasts results in accumulation extracellular matrix proteins that form fibrotic scar. Long noncoding RNAs regulate activity provide targets therapies. Approach Results: We identified long RNA TILAM located near COL1A1 , expressed HSCs, induced with humans mice. Loss-of-function studies...
Objectives: There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but been found to be also decrease C-reactive protein (CRP). Ondansetron a serotonin (5-HT3) receptor antagonist widely used prevent nausea vomiting patients receiving chemotherapy for cancer. Small studies suggested adjunctive ondansetron efficacious against symptoms. We carried out feasibility study (within 5 years of...
Abstract The homeostasis of the proteome depends on tight regulation mRNA and protein abundances, translation rates, lifetimes. Results from several studies prokaryotes or eukaryotic cell cultures have suggested that is connected to, perhaps regulated by, codon sequences. However, this has been little investigated for mammals in vivo . Moreover, link between coding sequences one critical parameter, lifetime, remained largely unexplored, both vitro We tested mouse brain, found percentages...
Chronic liver injury causes fibrosis, characterized by the formation of scar tissue resulting from excessive accumulation extracellular matrix (ECM) proteins. Hepatic stellate cell (HSC) myofibroblasts are primary type responsible for yet there currently no therapies directed at inhibiting activity HSC myofibroblasts. To search potential anti-fibrotic compounds, we performed a high-throughput compound screen in human and identified 19 small molecules that induce inactivation, including...
We present the Small RNA Expression Atlas (SEAweb), a web application that allows for interactive querying, visualization and analysis of known novel small RNAs across 10 organisms. It contains sRNA pathogen expression information over 4200 published samples with standardized search terms ontologies. In addition, SEAweb re-analysis 879 differential 514 classification comparisons. SEAweb's user model enables researchers to compare re-analyze user-specific datasets, highlighting common...
Depression is common among general trauma patients and associated with a poor outcome. We evaluated the relationship of psychological distress to physical injury, musculoskeletal complaints, social factors in low-income country.We administered Self-Rating Questionnaire (SRQ), Oslo support questionnaire, Brief Disability (BDQ).An SRQ score 9 or more, which indicates probable depressive disorder, occurred 45.6% men 76.1% women. A high was female sex, little no education, low income support....
The Medaka Expression Pattern Database (MEPD; http://mepd.cos.uni-heidelberg.de/) is designed as a repository of medaka expression data for the scientific community. In this update we present two main improvements. First, have changed previous clone-centric view in situ to gene-centric view. This possible because now linked all MEPD gene annotation ENSEMBL. addition, also connected genes their corresponding orthologous zebrafish, again using ENSEMBL database. Based on this, provide link...
A deep understanding of how regulation the multiple levels gene expression in mammalian tissues give rise to complex phenotypes has been impeded by cellular diversity. handful techniques were developed tag-select nucleic acids interest specific cell types, thereby enabling their capture. We expanded this strategy developing Tagger knock-in mouse line bearing a quad-cistronic transgene combining enrichment tools for nuclei, nascent RNA, translating mRNA, and mature microRNA (miRNA)....