A5031329520- Parasitic Infections and Diagnostics
- Immune Cell Function and Interaction
- Toxoplasma gondii Research Studies
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Amoebic Infections and Treatments
- Clostridium difficile and Clostridium perfringens research
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- Viral gastroenteritis research and epidemiology
- Cancer-related gene regulation
- Vector-Borne Animal Diseases
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Wnt/β-catenin signaling in development and cancer
- Cancer Immunotherapy and Biomarkers
- Coccidia and coccidiosis research
- Viral Infections and Immunology Research
- Epigenetics and DNA Methylation
- Pediatric health and respiratory diseases
- Cytokine Signaling Pathways and Interactions
- Reproductive System and Pregnancy
- Genomics and Chromatin Dynamics
- Lung Cancer Research Studies
University of Pennsylvania
2018-2024
One Cell Systems (United States)
2024
South University
2019-2023
University of Iowa
2015-2018
The apicomplexan parasite Cryptosporidium is a leading global cause of severe diarrhoeal disease and an important contributor to early childhood mortality. Currently, there are no fully effective treatments or vaccines available. Parasite transmission occurs through ingestion oocysts, either direct contact consumption contaminated water food. Oocysts meiotic spores the product sex. has single-host life cycle in which both asexual sexual processes occur intestine infected hosts. Here, we...
Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, growth faltering. Older children in high endemicity regions appear resistant infection, while previously unexposed adults remain susceptible. Experimental studies humans animals support the development resistance, but we do not understand mechanisms that underlie protective immunity Cryptosporidium. Here, derive vivo model infection immunocompetent C57BL/6 mice by...
Abstract In response to acute viral infection, activated naive T cells give rise effector that clear the pathogen and memory persist long-term provide heightened protection. cell factor 1 (Tcf1) is essential for several of these differentiation processes. Tcf1 expressed in multiple isoforms, with all isoforms sharing same HDAC DNA-binding domains long containing a unique N-terminal β-catenin–interacting domain. this study, we specifically ablated mice, while retaining expression short...
Ezh2 is an histone methyltransferase (HMT) that catalyzes H3K27me3 and functions in TH1, TH2, Treg cells primarily via HMT activity. Here we show ablation impairs T follicular helper (TFH) cell differentiation activation of the TFH transcription program. In cells, most Ezh2-occupied genomic sites, including Bcl6 promoter, are associated with H3K27ac rather than H3K27me3. Mechanistically, recruited by Tcf1 to directly activate transcription, this function requiring phosphorylation at Ser21....
Significance The intestinal immune system is able to control pathogens while tolerating and interpreting microbial cues from an abundant microbiome. mechanisms of innate recognition are crucial differentiating between pathogen commensal in this tissue mounting appropriate inflammatory response. Persistent inflammation can alter the cellular architecture physiology gut have lasting impact on nutritional state children who face frequent infection with certain enteric pathogens. We demonstrate...
The parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. invades enterocytes where it develops a unique intracellular niche. Infected cells exhibit profound changes morphology, physiology, transcriptional activity. How the effects these poorly understood. We explored localization of highly polymorphic proteins found members parvum MEDLE protein family to be translocated into cytosol infected cells. All life stages...
Cryptosporidium is a leading cause of severe diarrhea and diarrheal-related death in children worldwide. As an obligate intracellular parasite, relies on intestinal epithelial cells to provide niche for its growth survival, but little known about the contributions that infected cell makes this relationship. Here we conducted genome wide CRISPR/Cas9 knockout screen discover host genes influence parvum infection and/or survival. Gene enrichment analysis indicated interferon response,...
Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects T cell function. However, it has been a challenge to understand how this infection generates responses they mediate parasite control. Here, was engineered express effector protein (MEDLE-2) that contains the major histocompatibility complex-I restricted SIINFEKL epitope which is recognized by receptor transgenic OT-I(OVA-TCR-I) clusters of differentiation (CD)8+ cells. These modified parasites...
IL-33 is an alarmin required for resistance to the parasite Toxoplasma gondii , but its role in innate this organism unclear. Infection with T. promotes increased stromal cell expression of IL-33, and levels replication correlate release affected tissues. In response infection, a subset lymphoid cells (ILC) emerges composed IL-33R + NK ILC1s. Rag1 −/− mice, where ILC1 production IFN-γ mediate loss resulted reduced ILC responses replication. Furthermore, administration mice marked decrease...
Abstract T cell factor 1 (Tcf1) is essential for development; however, it remains controversial whether β-catenin, a known coactivator of Tcf1, has role. Tcf1 expressed in multiple isoforms lineage cells, with the long interacting β-catenin through an N-terminal domain. In this study, we specifically ablated mice (p45−/−mice) to abrogate interaction. Although thymic cellularity was diminished p45−/− mice, transition thymocytes maturation stages unaffected, no overt signs developmental...
Cryptosporidium is an enteric pathogen and a prominent cause of diarrheal disease worldwide. Control requires CD4+ T cells, but how protective cell responses are generated poorly understood. Here, parasites that express MHCII-restricted model antigens were to understand the basis for priming effector function. These studies revealed parasite-specific cells primed in draining mesenteric lymph node differentiate into Th1 gut provide local parasite control. Although type 1 conventional...
Abstract Cryptosporidium causes debilitating diarrheal disease in patients with primary and acquired defects T cell function. However, it has been a challenge to understand how this infection generates responses they mediate parasite control. Here, was engineered express effector protein (MEDLE-2) that contains the MHC-I restricted SIINFEKL epitope which is recognized by TCR transgenic OT-I CD8 + cells. These modified parasites induced expansion of endogenous SIINFEKL-specific cells were...
Abstract Cryptosporidium is an enteric pathogen that a prominent cause of diarrheal disease. Control this infection requires CD4 + T cells, though the processes lead to cell-mediated resistance have been difficult assess. Here, parasites express MHCII-restricted model antigens were generated dissect early events influence cell priming and effector function. These studies highlight parasite-specific cells are primed in draining mesenteric lymph node (mesLN) differentiate into Th1 gut, where...
ABSTRACT The parasite Cryptosporidium is responsible for diarrheal disease in young children causing death, malnutrition, and growth delay. invades enterocytes where it develops a unique intracellular niche. Infected cells exhibit profound changes morphology, physiology transcriptional activity. How the effects these poorly understood. We explored localization of highly polymorphic proteins found members C. parvum MEDLE protein family to be translocated into cytoplasm infected cells. All...
SUMMARY The intestinal parasite, Cryptosporidium , is a major contributor to global child mortality and causes opportunistic infection in immune deficient individuals. Innate resistance which specifically invades enterocytes, dependent on the production of IFN-γ, yet whether enterocytes contribute parasite control poorly understood. In this study, utilizing natural mouse pathogen, tyzzeri we show that epithelial-derived IL-18 synergized with IL-12 stimulate innate lymphoid cell (ILC) IFN-γ....
Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, growth faltering. Older children in high endemicity regions appear resistant infection, while previously unexposed adults remain susceptible as documented by large outbreaks the United States. Experimental studies humans animals support development resistance, but we do not understand mechanisms that underlie protective immunity Cryptosporidium. Here isolate...