A5062053457- Mosquito-borne diseases and control
- HIV Research and Treatment
- Viral Infections and Vectors
- RNA Research and Splicing
- Hepatitis C virus research
- RNA modifications and cancer
- Viral Infections and Outbreaks Research
- Virus-based gene therapy research
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Animal Virus Infections Studies
- Bacteriophages and microbial interactions
- Respiratory viral infections research
- Hepatitis B Virus Studies
- HIV/AIDS drug development and treatment
- Virology and Viral Diseases
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Plant Virus Research Studies
- Zoonotic diseases and public health
- HIV/AIDS Research and Interventions
- Vector-Borne Animal Diseases
- Malaria Research and Control
- Vector-borne infectious diseases
- Biosensors and Analytical Detection
Abbott Fund
2016-2025
Abbott (United States)
2018-2025
Abbott (United Kingdom)
2023
Stamatopoulos and Associates (Greece)
2019
Johns Hopkins University
2005-2014
University of Pennsylvania
2010-2013
Institute of Molecular Biology and Biophysics
2013
Howard Hughes Medical Institute
2010-2013
Georgetown University Medical Center
2005
Georgetown University
2005
Significance Spinal muscular atrophy (SMA), a common genetic motor neuron (MN) degenerative disease and leading hereditary cause of infant mortality, results from survival (SMN) protein deficiency. However, SMN’s ubiquitous expression housekeeping functions in biogenesis snRNPs, the spliceosome’s subunits, seems difficult to reconcile with SMA’s MN selective pathology. Here, we sequenced transcriptomes MNs adjacent white matter microdissected spinal cords presymptomatic SMA mice. This...
Mining the genome sequence of Burkholderia thailandensis MSMB43 revealed a cryptic biosynthetic gene cluster resembling that FR901464 (4), prototype spliceosome inhibitor produced by Pseudomonas sp. No. 2663. Transcriptional analysis cultivation condition in which regulatory is adequately expressed. Consequently, three new compounds, named thailanstatins A (1), B (2), and C (3), were isolated from fermentation broth B. MSMB43. Thailanstatins are proposed to be biosynthesized hybrid...
The full spectrum of HIV-1 diversity can be found in Central Africa, including 2 divergent strains collected 1983 and 1990 Democratic Republic Congo (DRC) that were preliminarily classified as group M subtype L. However, a third epidemiologically distinct L genome must identified to designate true subtype.Specimen CG-0018a-01 was 2001 DRC part an HIV study. Previous subgenomic sequences from this specimen branched closely with proposed references. Metagenomic next-generation sequencing...
Arbovirus infections are frequent causes of acute febrile illness (AFI) in tropical countries. We conducted health facility-based AFI surveillance at four sites Colombia (Cucuta, Cali, Villavicencio, Leticia) during 2019-2022. Demographic, clinical and risk factor data were collected from persons with that consented to participate the study (n = 2,967). Serologic specimens obtained tested for multiple pathogens by RT-PCR rapid test (Antigen/IgM), 20.7% identified as dengue positive combined...
Bioactive compounds have been invaluable for dissecting the mechanisms, regulation, and functions of cellular processes. However, very few such reagents described pre-mRNA splicing. To facilitate their systematic discovery, we developed a high-throughput cell-based assay that measures splicing by utilizing quantitative reporter system with advantageous features. The reporter, consisting destabilized, intron-containing luciferase expressed from short-lived mRNA, allows rapid screens (<4 h),...
Eukaryotes have two types of spliceosomes, comprised either major (U1, U2, U4, U5, U6) or minor (U11, U12, U4atac, U6atac; <1%) snRNPs. The high conservation introns, typically one amidst many introns in several hundred genes, despite their poor splicing, has been a long-standing enigma. Here, we discovered that the low abundance spliceosome’s catalytic snRNP, U6atac, is strikingly unstable (t½<2 hr). We show U6atac level depends on both RNA polymerases II and III can be rapidly...
Hepatitis C virus (HCV) and human pegivirus (HPgV), formerly GBV-C, are the only known viruses in Hepacivirus Pegivirus genera, respectively, of family Flaviviridae. We present discovery a second pegivirus, provisionally designated 2 (HPgV-2), by next-generation sequencing plasma from an HCV-infected patient with multiple bloodborne exposures who died sepsis unknown etiology. HPgV-2 is highly divergent, situated on deep phylogenetic branch clade that includes rodent bat pegiviruses, which it...
Viral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and their impact on test performance.
In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel lineage were documented in the Amazon Region Brazil. We report introduction this into Colombia and its co-circulation with another OROV lineage. Continued surveillance is needed prevent further spread Americas.
Molecular surveillance is essential to monitor HIV diversity and track emerging strains. We have developed a universal library preparation method (HIV-SMART [i.e.,switchingmechanismat 5' end ofRNAtranscript]) for next-generation sequencing that harnesses the specificity of HIV-directed priming enable full genome characterization all HIV-1 groups (M, N, O, P) HIV-2. Broad application HIV-SMART approach was demonstrated using panel diverse cell-cultured virus isolates. non-subtype B-infected...
While diagnosis of COVID-19 relies on qualitative molecular testing for the absence or presence SARS-CoV-2 RNA, quantitative viral load determination has many potential applications in antiviral therapy and vaccine trials as well implications public health quarantine guidance. To date, no tests have been authorized clinical use by FDA. In this study, we modified FDA emergency RealTime assay into a Laboratory Developed Test (LDT) using newly developed Abbott calibration standards. Both...
Introduction Mayaro Fever (MF) is a tropical disease caused by the virus (MAYV), with outbreaks documented in Latin America. Methods A hospital-based fever surveillance Leticia, Colombian Amazon, collected sera from 1,460 patients aged 5-89 between December 2020 and April 2023. Results Dengue malaria were main diagnoses (19.4 5.8%, respectively), leaving 71.4% of cases unidentified after testing. Metagenomic sequencing real-time RT-qPCR testing identified MAYV two (25-year-old male an...
Between April and November 2023, 27 unexplained human deaths that presented with swelling of the arms, skin sores black centers, difficulty in breathing, obstructed swallowing, headaches, other body aches were reported Kyotera District, Uganda by Public Health Emergency Operations Center. Subsequently, death cattle on farms consumption carcass meat some residents also reported. Field response teams collected clinical/epidemiological data autopsy samples to determine cause deaths. Metagenomic...
Surveillance of acute respiratory infection (ARI) informs vaccination, preventive, and management decisions. In many countries, immunofluorescence is the cornerstone for ARI surveillance. We aimed to determine effect adding multiplex polymerase chain reaction (mPCR) conventional surveillance in ARI. Respiratory samples from patients with influenza-like illness (ILI) severe (SARI) were tested by a approach [direct (DIF) SARS-CoV-2 PCR, subset underwent routine testing]. Negative specimens PCR...
Abstract Background Murine and scrub typhus are common causes of acute undifferentiated fever (AUF) in tropical regions, after malaria, dengue fever, typhoid have been ruled out. While indirect immunofluorescence assay (IFA) can diagnose both diseases, accuracy depends on when the sample is collected. To improve detection, we used unbiased metagenomic Next Generation Sequencing (mNGS) 969 AUF patient samples with negative IFA results from Siriraj Hospital, Bangkok, Thailand collected between...
Abstract Background Adenovirus (HAdV) is a common cause of acute respiratory infection (ARI). In healthy people, infections are usually mild and self-limiting. However, during the second half 2022, an HAdV severe (SARI) outbreak occurred in Colombia. Although epidemiological data South America scarce, SARS-CoV-2 pre-pandemic studies reported HAdV-B3 as main adenoviral infections. Our study investigated circulating genotype before, during, after this along with clinical associated.Figure 1....
Yellow fever virus (YFV) is an arbovirus that causes acute febrile illness (AFI), in tropical areas of South America and Africa. Through a 2020-2023 AFI study Leticia, Colombia, leveraging metagenomic next-generation sequencing (mNGS), we identified isolated YFV (LET1450). Phylogenetic analysis showed this strain belongs to American genotype II (SamII), linked Peruvian Bolivian sequences emerging around 1989. Phylodynamic indicates these strains, with unique genetic makeup, could have...
Given the dynamic changes in HIV-1 complexity and diversity, next-generation sequencing (NGS) has potential to revolutionize strategies for effective HIV global surveillance. In this study, we explore utility of metagenomic NGS characterize divergent strains simultaneously screen other co-infecting viruses. Thirty-five HIV-1-infected Cameroonian blood donor specimens with viral loads >4.4 log10 copies/ml were selected include a diverse representation group M strains. Random-primed libraries,...
Surveillance of emerging viral variants is critical to ensuring that blood screening and diagnostic tests detect all infections regardless strain or geographic location. In this study, we conducted serological molecular surveillance monitor the prevalence diversity HIV, HBV, HTLV in South Cameroon. The HIV was 8.53%, HBV 10.45%, 1.04% amongst study participants. Molecular characterization 555 HIV-1 specimens identified incredible diversity, including 7 subtypes, 12 CRFs, 6 unclassified, 24...
Metagenomic next-generation sequencing (mNGS) has enabled the high-throughput multiplexed identification of sequences from microbes potential medical relevance. This approach become indispensable for viral pathogen discovery and broad-based surveillance emerging or re-emerging pathogens. From 2015 to 2019, plasma was collected 9586 individuals in Cameroon Democratic Republic Congo enrolled a combined hepatitis virus retrovirus program. A subset (n = 726) patient specimens analyzed by mNGS...
Acute febrile illnesses (AFI) in developing tropical and sub-tropical nations are challenging to diagnose due the numerous causes non-specific symptoms. The proliferation of rapid diagnostic testing successful control campaigns against malaria have revealed that non-