A5102900419- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Genetics and Neurodevelopmental Disorders
- Cellular transport and secretion
- Immune cells in cancer
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Single-cell and spatial transcriptomics
- Genetic Associations and Epidemiology
- Endoplasmic Reticulum Stress and Disease
- Genomics and Rare Diseases
- Transplantation: Methods and Outcomes
- T-cell and B-cell Immunology
- Lysosomal Storage Disorders Research
- ATP Synthase and ATPases Research
- Ubiquitin and proteasome pathways
- Diabetes and associated disorders
- HIV Research and Treatment
- CRISPR and Genetic Engineering
- Autoimmune and Inflammatory Disorders Research
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- Reproductive System and Pregnancy
- Hereditary Neurological Disorders
Brigham and Women's Hospital
2023-2024
Harvard University
2023-2024
Washington University in St. Louis
2015-2023
St. Louis Children's Hospital
2021-2023
Arabian Gulf University
2021
Queen's University
2021
Mallinckrodt (United States)
2021
St. Jude Children's Research Hospital
2018
There has been increasing recognition of the importance cellular metabolism and metabolic substrates for function differentiation immune cells. In this study, first time to our knowledge, we investigate requirements production IFN-γ by freshly isolated NK Primary murine cells mainly use mitochondrial oxidative phosphorylation at rest with short-term activation. Remarkably, discovered significant differences in cell depending upon activation signal. Stimulation was independent glycolysis or...
NK cell activation has been shown to be metabolically regulated in vitro; however, the role of metabolism during vivo responses infection is unknown. We examined glycolysis function murine cytomegalovirus (MCMV) and ability IL-15 prime cells CMV infection. The glucose inhibitor 2-deoxy-ᴅ-glucose (2DG) impaired both mouse human cytotoxicity following priming vitro. Similarly, MCMV-infected mice treated with 2DG had clearance NK-specific targets vivo, which was associated higher viral burden...
CaCO
<h3>Objective</h3> To report 6 new patients with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome. <h3>Methods</h3> Clinical exome or targeted sequencing were performed to elucidate the molecular genetic cause in neurocognitive abnormalities brain imaging findings. <h3>Results</h3> CEDNIK syndrome is a rare condition caused by biallelic pathogenic loss-of-function variants synaptosomal-associated protein 29 (<i>SNAP29</i>), which encodes vesicular membrane...
Abstract / Summary Paragraph Genetic studies have identified thousands of individual disease-associated non-coding alleles, but identification the causal alleles and their functions remain critical bottlenecks. Even though CRISPR-Cas editing has enabled targeted modification DNA, inefficient leads to heterogeneous outcomes across cells, limiting ability detect functional consequences disease alleles. To overcome these challenges, we present a multi-omic single cell sequencing approach that...
ABSTRACT Purpose Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 encodes a core member of the protein complex that methylates histone 3 lysine-4 (H3K4) and not implicated in human disease. Methods We identify five unrelated individuals de novo heterozygous pathogenic variants . Three truncating two missense were identified probands neurodevelopmental symptoms including global developmental delay, intellectual disability, microcephaly, short stature. Here, we...
ABSTRACT Valosin-containing protein (VCP) is an AAA+ ATPase that plays critical roles in multiple ubiquitin-dependent cellular processes. Dominant pathogenic variants VCP are associated with adult-onset multisystem proteinopathy (MSP) presents myopathy, bone disease, dementia, and/or motor neuron disease. Through GeneMatcher, we identified 13 unrelated individuals who carry novel heterozygous (12 de novo , 1 inherited) a childhood-onset disorder characterized by developmental delay,...
Introductory Paragraph To understand genetic mechanisms driving disease, it is essential but difficult to map how risk alleles affect the composition of cells present in body. Single-cell profiling quantifies granular information about tissues, variant-associated cell states may reflect diverse combinations profiled features that are challenging predefine. We introduce GeNA (Genotype-Neighborhood Associations), a statistical tool identify state abundance quantitative trait loci (csaQTLs)...
MicroRNAs (miRNAs) are highly conserved non-coding RNAs that regulate gene expression by translational repression or mRNA degradation. MiRNAs as immune regulators may govern of genes relevant to allograft rejection, tolerance induction and post-transplant infection in recipients organ transplants. We performed a broad analysis on miRNAs expressed lymphocytes functions post-transplant. Groups syngeneic (C57BL/6 → C57BL/6) allogeneic (BALB/c →C57BL/6) (n=3-9) heterotopic heart transplants were...
Abstract Studies in diverse cell types have rediscovered the importance of basic cellular metabolism regulating immune responses. For example, glycolytic and oxidative are counter-regulated T cells to develop inflammatory effectors vs. memory regulatory cells, respectively. NK which first responders viral infection malignant transformation, may be similarly regulated. We recently showed that cytotoxic activity during with murine cytomegalovirus (MCMV) required glucose metabolism, whereas...