A5018561104- Inflammasome and immune disorders
- interferon and immune responses
- Malaria Research and Control
- Cell death mechanisms and regulation
- Mosquito-borne diseases and control
- Heme Oxygenase-1 and Carbon Monoxide
- Autophagy in Disease and Therapy
- Invertebrate Immune Response Mechanisms
- Drug Transport and Resistance Mechanisms
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Hepatitis B Virus Studies
- Liver Disease Diagnosis and Treatment
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Trace Elements in Health
- Immune responses and vaccinations
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Cancer, Lipids, and Metabolism
- Insect Pest Control Strategies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mitochondrial Function and Pathology
- Antibiotic Resistance in Bacteria
- Gout, Hyperuricemia, Uric Acid
St. Jude Children's Research Hospital
2020-2025
University of Florida
2018-2021
Johns Hopkins University
2014-2019
Johns Hopkins Medicine
2018
NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated inflammatory infectious diseases, but little known about its function as innate immune sensor cell death regulator. Therefore, we screened for NLRC5's role in response infections, PAMPs, DAMPs, cytokines. We identified acts drive death, PANoptosis, specific ligands,...
Malaria sporozoites are deposited into the skin by mosquitoes and infect hepatocytes. The molecular basis of how Plasmodium falciparum migrate through host cells is poorly understood, direct evidence its importance in vivo lacking. Here, we generated traversal-deficient genetic disruption sporozoite microneme protein essential for cell traversal (PfSPECT) or perforin-like 1 (PfPLP1). Loss either gene did not affect P. growth erythrocytes, contrast with a previous report that PfPLP1 merozoite...
Innate immunity provides the critical first line of defense in response to pathogens and sterile insults. A key mechanistic component this is initiation innate immune programmed cell death (PCD) eliminate infected or damaged cells propagate responses. However, excess PCD associated with inflammation pathology. Therefore, understanding activation regulation a central aspect characterizing responses identifying new therapeutic targets across disease spectrum. This protocol methods for by...
Innate immunity provides the critical first line of defense against infection and sterile triggers. Cell death is a key component innate immune response to clear pathogens, but excessive or aberrant cell can induce inflammation, cytokine storm, pathology, making it central molecular mechanism in inflammatory diseases. Alcohol-associated liver disease (ALD) one such disease, specific mechanisms driving pathology this context remain unclear. Here, by leveraging RNAseq tissue expression...
The past 20 years of research has elucidated new innate immune sensing and cell death pathways with disease relevance. Future molecular characterization these their crosstalk functional redundancies will aid in development therapeutic strategies.
In vitro studies of liver stage (LS) development the human malaria parasite Plasmodium falciparum are technically challenging; therefore, fundamental questions about hepatocyte receptors for invasion that can be targeted to prevent infection remain unanswered. To identify novel and further understand susceptibility P. sporozoite invasion, we created an optimized in system by mimicking vivo conditions using subcloned HC-04.J7 cell line supports mean rates 3-5% early exoerythrocytic forms—a 3-...
Abstract Malaria transmission-blocking vaccines (TBVs) prevent the completion of developmental lifecycle malarial parasites within mosquito vector, effectively blocking subsequent infections. The midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent (T-B) antibodies, informing design next-generation AnAPN1. Here, we functionally screened new immunogens and...
The routine study of human malaria liver-stage biology in vitro is hampered by low infection efficiency hepatocellular carcinoma (HCC) lines (<0.1%), poor understanding steady-state HCC biology, and lack appropriate tools for trace sample analysis. HC-04 the only that supports complete development parasites. We hypothesized HCCs are various intermediate stages epithelial-mesenchymal transition (EMT) HC-04s retain epithelial characteristics permit infection. developed a facile analytical...
The liver stage of the Plasmodium life cycle features sporozoite traversal sinusoidal barrier through Kupffer cells (KCs) followed by invasion hepatocytes. Little is known about interaction sporozoites with KCs, liver-resident macrophages. Previous reports suggest KCs do not mount a pro-inflammatory response and undergo cell death following this interaction. Our work explores using primary rat (PRKCs) berghei sporozoites. We analyzed PRKC culture supernatants for markers an immunological...
Invading pathogens and homeostatic perturbations activate the innate immune system as body's first line of defense. Innate immunity is driven by pattern recognition receptors (PRRs),1 which can by: 1) acting direct that bind specific pathogen-associated molecular patterns (PAMPs) or endogenous damage-associated (DAMPs), 2) sensing responding to caused PAMPs DAMPs. In both cases, PRR activation drives downstream signalling induce a broader response, inflammation, regulated cell death. The...
Thrombospondin type I repeat (TSR) domains are commonly O-fucosylated by protein O-fucosyltransferase 2 (PoFUT2), and this modification is required for optimal folding secretion of TSR-containing proteins. The human malaria parasite Plasmodium falciparum expresses proteins containing TSR domains, such as the thrombospondin-related anonymous (TRAP) circumsporozoite surface (CSP), which O-fucosylated. TRAP CSP present on sporozoites play essential roles in mosquito host invasion processes...
Malaria is a major global health threat, with nearly half the world's population at risk of infection. Given recently described delayed clearance parasites by artemisinin-combined therapies, new antimalarials are needed to facilitate effort toward elimination and eradication. NPC1161 an 8-aminoquinoline that derived from primaquine improved therapeutic profile compared parent compound. The (R)-(-) enantiomer (NPC1161B) has lower effective dose results in decreased toxic side effects such as...
Kupffer cells (KCs) are the first line of defense in liver against pathogens, yet several microbes successfully target liver, bypass immune surveillance, and effectively develop this tissue. Our current, albeit poor, understanding KC–pathogen interactions has been largely achieved through study primary cells, requiring isolation from large numbers animals. To facilitate KC biology, an immortalized rat 1, RKC1, was developed. We performed a comparative global proteomic analysis RKC1 KCs...
Abstract Background: Rigosertib (ON 01910.Na) is considered a promising anticancer agent due to its ability inhibit multiple disease signaling pathways, including RAS-MAPK signaling. in Phase 2 program advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) (NCT03786237, NCT04177498), and trial combination with pembrolizumab patients metastatic melanoma (NCT05764395). The aim of our study was further elucidate the mechanism action...