Caroline J. Duncombe

ORCID: 0000-0002-4356-6317
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About
Contact & Profiles
Research Areas
  • Malaria Research and Control
  • Mosquito-borne diseases and control
  • Tuberculosis Research and Epidemiology
  • Complement system in diseases
  • Biochemical and Molecular Research
  • Quinazolinone synthesis and applications
  • Vector-borne infectious diseases
  • Immune Cell Function and Interaction
  • Inflammasome and immune disorders
  • SARS-CoV-2 and COVID-19 Research
  • COVID-19 Impact on Reproduction
  • Global Maternal and Child Health
  • RNA Interference and Gene Delivery
  • Monoclonal and Polyclonal Antibodies Research
  • Mycobacterium research and diagnosis
  • Tryptophan and brain disorders
  • Trauma and Emergency Care Studies
  • Long-Term Effects of COVID-19
  • Vaccine Coverage and Hesitancy
  • Crystallization and Solubility Studies
  • X-ray Diffraction in Crystallography

National Institutes of Health
2020-2025

University of Washington
2021-2025

National Institute of Allergy and Infectious Diseases
2021

Wexham Park Hospital
2014

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation 309 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data patient-reported symptoms. resolved four PASC-anticipating at the time diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, specific...

10.1016/j.cell.2022.01.014 article EN cc-by Cell 2022-01-25

Background: Prior to infecting red blood cells and causing the clinical manifestations of malaria, hepatotropic parasite Plasmodium falciparum undergoes a complex liver stage. Biological sex-based differences in pathogenesis by microorganisms are well-documented, but unstudied for P. humans. We conducted pooled analysis on data from participants placebo arms infectivity controls Controlled Human Malaria Infection (CHMI) trials malaria-naïve populations evaluate impact biological sex time...

10.2139/ssrn.5087394 preprint EN 2025-01-01

Pyrazolo[1,5-a]pyrimidin-7(4H)-one was identified through high-throughput whole-cell screening as a potential antituberculosis lead. The core of this scaffold has been several times previously and associated with various modes action against Mycobacterium tuberculosis (Mtb). We explored the synthesis focused library analogues key features pharmacophore while achieving substantial improvements in antitubercular activity. Our best hits had low cytotoxicity showed promising activity Mtb within...

10.1021/acsinfecdis.0c00851 article EN cc-by ACS Infectious Diseases 2021-01-06

Tryptophan biosynthesis represents an important potential drug target for new anti-TB drugs. We identified a series of indole-4-carboxamides with potent antitubercular activity. In vitro, Mycobacterium tuberculosis (Mtb) acquired resistance to these compounds through three discrete mechanisms: (1) decrease in metabolism via loss-of-function mutations the amidase that hydrolyses carboxamides, (2) increased biosynthetic rate tryptophan precursors loss allosteric feedback inhibition...

10.1016/j.chembiol.2021.02.023 article EN cc-by Cell chemical biology 2021-03-24

Abstract Radiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage Plasmodium infection by inducing liver-resident memory CD8 + T cells to target parasites in the liver. Such be induced ‘Prime-and-trap’ vaccination, which here combines DNA priming against P. yoelii circumsporozoite protein (CSP) with a subsequent intravenous (IV) dose of liver-homing RAS “trap” activated and expanding Prime-and-trap confers durable protection mice, efforts are underway translate this...

10.1038/s41598-024-53118-9 article EN cc-by Scientific Reports 2024-02-04

Abstract Background Plasmodium knowlesi is an established experimental model for basic and pre-clinical malaria vaccine research. Historically, rhesus macaques have been the most common host studies with P. parasites. However, are not natural hosts , there interest in identifying alternative The study team previously reported that pig-tailed (PTM), a could be challenged cryopreserved sporozoites (PkSPZ), time to blood stage infection equivalent rhesus. Here, additional exploratory were...

10.1186/s12936-023-04788-9 article EN cc-by Malaria Journal 2023-12-13

Tryptophan biosynthesis represents an important potential drug target for new anti-TB drugs. We identified a series of indole-4-carboxamides with potent antitubercular activity. In vitro, Mycobacterium tuberculosis (Mtb) acquired resistance to these compounds through three discrete mechanisms: (1) decrease in metabolism via loss-of-function mutations the amidase that hydrolyses carboxamides, (2) increased biosynthetic rate tryptophan precursors loss allosteric feedback inhibition...

10.2139/ssrn.3724670 article EN SSRN Electronic Journal 2020-01-01

7DW8-5 is a potent glycolipid adjuvant that improves malaria vaccine efficacy in mice by inducing IFN-γ and increasing protective CD8+ T cell responses. The addition of was previously shown to improve the cell-mediated heterologous 'prime-and-trap' against Plasmodium yoelii sporozoite challenge inbred female mice. Here, we report significant differential sex-specific responses outbred Male express significantly less IL-4 compared females following intravenous administration. Additionally,...

10.3390/biom13010008 article EN cc-by Biomolecules 2022-12-21

The Collaborative Action in Lowering Maternity Encountered Deaths (CALMED) aims to send vocational training teams (VTTs) help reduce maternal and newborn mortality. This article outlines two midwives' experience during a 2-week VTT programme manage obstetric emergencies India March 2013. CALMED project was organised by Rotary groups London Mumbai.

10.12968/bjom.2014.22.5.357 article EN British Journal of Midwifery 2014-05-02

Abstract Malaria is caused by Plasmodium parasites and was responsible for over 247 million infections 619,000 deaths in 2021. Radiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage infection inducing protective liver-resident memory CD8 + T cells. Such cells be induced ‘prime-and-trap’ vaccination, which here combines DNA priming against the P. yoelii circumsporozoite protein (CSP) with a subsequent intravenous (IV) dose of liver-homing RAS to “trap” activated...

10.21203/rs.3.rs-3243319/v1 preprint EN cc-by Research Square (Research Square) 2023-08-11

Abstract Background Plasmodium knowlesi (Pk) is an established experimental model for basic and pre-clinical malaria vaccine research. Historically, rhesus macaques have been the most common host studies with Pk parasites. However, are not natural hosts Pk, there interest in identifying alternative The study team previously reported that pig-tailed (PTM), a could be challenged cryopreserved sporozoites (PkSPZ), time to blood stage infection equivalent rhesus. Here, additional exploratory...

10.21203/rs.3.rs-3283109/v1 preprint EN cc-by Research Square (Research Square) 2023-08-25

Abstract Generating liver resident-memory CD8+ T cells (TRM cells) is critical for effective liver-stage malaria vaccine. The role of biological sex in vaccine protection understudied. Here we report sex-specific immune responses and outcomes the two-step heterologous ‘Prime-and-Trap’ designed to induce TRM cells. Prime-and-Trap strategy combines sporozoite antigen DNA priming with a single intravenous dose liver-homing radiation-attenuated sporozoites (RAS) direct “trap” activated expanding...

10.4049/jimmunol.208.supp.181.14 article EN The Journal of Immunology 2022-05-01
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