A5007835427- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Genomic variations and chromosomal abnormalities
- Molecular Biology Techniques and Applications
- interferon and immune responses
- Chromosomal and Genetic Variations
- Mycobacterium research and diagnosis
- Ubiquitin and proteasome pathways
- Gene expression and cancer classification
- Fungal and yeast genetics research
- Melanoma and MAPK Pathways
- Systemic Sclerosis and Related Diseases
- DNA and Nucleic Acid Chemistry
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- RNA regulation and disease
- Genetic Syndromes and Imprinting
- Radiomics and Machine Learning in Medical Imaging
- Hidradenitis Suppurativa and Treatments
- Nuclear Structure and Function
Washington University in St. Louis
2015-2025
University of Missouri–St. Louis
2022
Helsinki University Hospital
2017
Institute for Molecular Medicine Finland
2017
University of Helsinki
2017
Johns Hopkins University
2007-2012
University of Washington
2012
Johns Hopkins Medicine
2007-2011
Kennedy Krieger Institute
2007-2009
An Eye on Metastasis Despite the considerable progress being made in elucidating cell biology of metastasis, little is known about genetic alterations that promote metastasis human tumors, cause most cancer deaths. A potentially important clue now emerges from work Harbour et al. (p. 1410 , published online 4 November), who used an exome-sequencing approach to search for mutations uveal melanomas, eye associated with a high rate fatal metastasis. Remarkably, over 80% tumor samples metastatic...
Little is known about molecular changes occurring within retinal ganglion cells (RGCs) before their death in glaucoma. Taking advantage of the fact that γ-synuclein (Sncg) mRNA expressed specifically and highly adult mouse RGCs, we show DBA/2J model glaucoma there not only a loss expressing this gene, but also downregulation gene expression Sncg many other genes large numbers RGCs. This RGCs occurs together with reductions FluoroGold (FG) retrograde transport. Surprisingly, are...
Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder autosomal-dominant inheritance and high penetrance, but the causative genetic mutation unknown.We have now identified four truncating mutations involving gene PRRT2 in vast majority (24/25) of well-characterized families PKD/IC.PRRT2 were also detected 28 78 additional families.PRRT2 encodes a proline-rich transmembrane protein unknown function that has been reported to interact t-SNARE,...
Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, impacts susceptibility recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection,...
It is an assumption of large, population-based datasets that samples are annotated accurately whether they correspond to known relationships or unrelated individuals. These annotations key for a broad range genetics applications. While many methods available assess relatedness involve estimates identity-by-descent (IBD) and/or identity-by-state (IBS) allele-sharing proportions, we developed novel approach IBD0, 1, and 2 based on observed IBS within windows. When combined with genome-wide...
Purpose: Age-related macular degeneration (AMD) has a substantial genetic risk component, as evidenced by the from common variants uncovered in first genome-wide association studies. More recently, it become apparent that rare also play an independent role AMD risk. We sought to determine if complement factor H (CFH) played Methods: had previously collected DNA large population of patients with advanced age-related (A-AMD) and controls for targeted deep sequencing candidate genes. In this...
Aberrant immune responses against gut microbiota are thought to be key drivers of inflammatory bowel disease (IBD) pathogenesis. However, the extent and targets immunoglobulin (Ig) A versus IgG bacteria in IBD its association with severity is not well understood. Here, we address this by analyzing fecal samples from Crohn's (CD), ulcerative colitis (UC), Non-IBD patients flow cytometry for frequency that were endogenously bound IgA and/or IgG. Assessment two geographically distinct cohorts...
Abstract Age-related microangiopathy, also known as small vessel disease (SVD), causes damage to the brain, retina, liver, and kidney. Based on DNA theory of aging, we reasoned that genomic instability may underlie an SVD caused by dominant C-terminal variants in TREX1, most abundant 3′−5′ exonuclease mammals. TREX1 cause adult-onset retinal vasculopathy with cerebral leukoencephalopathy (RVCL or RVCL-S). In RVCL, aberrant, C-terminally truncated mislocalizes nucleus due deletion its...
HLA-B*27 was one of the first HLA alleles associated with an autoimmune disease, i.e., axial spondyloarthritis (axSpA) and acute anterior uveitis (B27AAU), which cause joint eye inflammation, respectively. Gastrointestinal inflammation has been suggested as a trigger axSpA. We recently identified bacterial peptide (YeiH) that can be presented by to expanded public T cell receptors (TCRs) in axSpA B27AAU. While YeiH is present enteric microbiota pathogens, additional evidence pathogenic cells...
Translational research is often a collaborative enterprise that involves basic science researchers, clinicians, and experts in genomics bioinformatics. While there are central university industry cores to support data generation, long-term storage falls the individual investigators. We frequently fulfill role of FASTQ file for our collaborators. To reduce cold space, we tested space savings gzip zstandard algorithms on an old set files. found had better overall compression ratio than best...
A mucosal infectious disease episode can render the host either more or less susceptible to recurrent infection, but specific mechanisms that tip balance remain unclear. We investigated this question in a mouse model of urinary tract infection and found prior bladder resulted an earlier onset tumor necrosis factor-alpha (TNFɑ)-mediated inflammation upon subsequent bacterial challenge, relative age-matched naive mice. However, duration TNFɑ signaling activation differed according whether...
In juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, weakness is accompanied by a characteristic rash that often becomes chronic and associated with vascular damage. We hoped to understand molecular underpinnings of JDM, particularly when untreated, which would facilitate identification novel mechanisms clinical targets might disrupt disease progression. studied RNA-Seq data from untreated JDM peripheral blood mononuclear cells (PBMCs; n = 11), PBMCs subset...
A variety of alterations occur in chromosomal DNA, many which can be detected using high density single nucleotide polymorphism (SNP) microarrays. These include deletions and duplications (assessed by observing changes copy number) regions homozygosity. The analysis SNP data from trios provide an additional category information about the nature origin inheritance patterns, including uniparental disomy (UPD), loss transmitted allele (LTA), nonparental relationship. main purpose SNPtrio is to...
STING gain-of-function causes autoimmunity and immunodeficiency in mice STING-associated vasculopathy with onset infancy (SAVI) humans. Here, we report that prevents development of lymph nodes Peyer's patches. We show the absence secondary lymphoid organs is associated diminished numbers innate cells (ILCs), including tissue inducer (LTi) cells. Although wild-type (WT) α4β7+ progenitors differentiate efficiently into LTi cells, do not. Furthermore, impairs all types ILCs. Patients mutations...
The tissue-specific drivers of neurosarcoidosis remain poorly defined. To identify cerebrospinal fluid (CSF) specific, antigen-driven T and B cell responses, we performed single-cell RNA sequencing CSF blood cells from neurosarcoid participants coupled to receptor sequencing. In contrast pulmonary sarcoidosis, which is driven by CD4 cells, found CD8 clonal expansion enriched in the CSF. These CSF-enriched were composed two subsets with differential expression EBI2, CXCR3, CXCR4. Lastly, our...