A5048782180- Immune Cell Function and Interaction
- Gut microbiota and health
- IL-33, ST2, and ILC Pathways
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Bacterial Infections and Vaccines
- Clostridium difficile and Clostridium perfringens research
- Digestive system and related health
- Immune Response and Inflammation
- COVID-19 Impact on Reproduction
- Diet and metabolism studies
- Amoebic Infections and Treatments
- Immune responses and vaccinations
- Metabolism, Diabetes, and Cancer
- Inflammasome and immune disorders
- Pancreatic function and diabetes
- Infant Nutrition and Health
- Asthma and respiratory diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Legionella and Acanthamoeba research
- Phagocytosis and Immune Regulation
- Infective Endocarditis Diagnosis and Management
- Microscopic Colitis
- Tryptophan and brain disorders
- Fluorine in Organic Chemistry
University of Toronto
2019-2024
University of California, San Francisco
2024
Richard King Mellon Foundation
2018-2023
Children's Hospital of Pittsburgh
2017-2023
University of Pittsburgh
2015-2023
College of Wooster
2013-2014
The innate immune system shapes brain development and is implicated in neurodevelopmental diseases. It critical to define the relevant cells signals their impact on circuits. In this work, we found that group 2 lymphoid (ILC2s) cytokine interleukin-13 (IL-13) signaled directly inhibitory interneurons increase synapse density developing mouse brain. ILC2s expanded produced IL-13 meninges. Loss of or signaling decreased inhibitory, but not excitatory, cortical synapses. Conversely, were...
Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on host's immune homeostasis, typically by elevating anti-microbial host defense. Tritrichomonas musculis, protozoan gut commensal, strengthens defense against enteric Salmonella infections through Asc- and Il1r1-dependent Th1 Th17 cell activation. However, underlying inflammasomes mediating this effect remain unknown. In study, we...
Maintaining macrophage (MΦ) heterogeneity is critical to ensure intestinal tissue homeostasis and host defense. The gut microbiota factors are thought synergistically guide MΦ development, although the exact nature, regulation, location of such collaboration remain unclear. Here, we report that microbial biochemical energy metabolism promotes colony-stimulating factor 2 (CSF2) production by group 3 innate lymphoid cells (ILC3s) within solitary isolated tissues (SILTs) in a cell-extrinsic,...
Background & AimsThe colonic epithelium requires continuous renewal by crypt resident intestinal stem cells (ISCs) and transit-amplifying (TA) to maintain barrier integrity, especially after inflammatory damage. The diet of high-income countries contains increasing amounts sugar, such as sucrose. ISCs TA are sensitive dietary metabolites, but whether excess sugar affects their function directly is unknown.MethodsHere, we used a combination 3-dimensional colonoids mouse model colon...
Abstract Inflammatory bowel disease has been associated with the dysregulation of T cells specific to Ags derived from intestinal microbiota. How microbiota-specific are regulated is not completely clear but believed be mediated by a combination IgA, regulatory cells, and type 3 innate lymphoid cells. To test role these components on we bred CBir1 TCR transgenic (CBir1Tg) mice (specific flagellin common bacteria) onto lymphopenic Rag1−/− background. Surprisingly, CBir1Tg background could...
Immunoglobulin (Ig) A supports mucosal immune homeostasis and host–microbiota interactions. While commensal bacteria are known for their ability to promote IgA, the role of non-bacterial microbes in induction IgA remains elusive. Here, we demonstrate that permanent colonization with protozoan Tritrichomonas musculis (T.mu) promotes T cell–dependent, class-switch recombination, intestinal accumulation IgA-secreting plasma cells (PC). T.mu specifically drives expansion follicular helper a...
Allogeneic hematopoietic stem cell transplantation is a viable treatment for multiple hematologic diseases, but its application often limited by graft-versus-host disease (GVHD), where donor T cells attack host tissues in the skin, liver, and gastrointestinal tract. Here, we examined role of cellular energy sensor AMP kinase (AMPK) alloreactive during GVHD development. Early posttransplant, AMPK activity increased more than 15-fold allogeneic cells, deficient both AMPKα1 AMPKα2 decreased...
Summary Maintaining intestinal macrophage (MP) heterogeneity is critical to ensure tissue homeostasis and host defense. The gut microbiota factors are thought synergistically shape colonic MP development, although there remains a fundamental gap in our understanding of the details such collaboration. Here, we report tertiary lymphoid organs (TLOs), enriched group 3 innate cells (ILC3s), as microbiota-operated niche for development monocyte-derived MPs. ILC3-derived colony stimulating factor...
ABSTRACT Immunoglobulin(Ig) A antibodies are the most abundant supporting mucosal immune homeostasis and host-microbiota interactions. Driven by gut commensal microbes, IgA-secreting plasma cells (PC) differentiate through T cell-dependent (Td) or cell independent (Ti) mechanisms. While bacteria within microbiota known for their ability to promote IgA, role of non-bacterial microbes on induction IgA remains elusive. Here, we demonstrate that permanent colonization with protozoan...
Abstract Allogeneic blood and marrow transplantation cures a variety of hematologic disorders, but its broader use remains limited by acute graft-versus-host disease (GVHD), where donor T cells attack destroy host tissues. To explore this process mechanistically, we elucidated the role AMP-activated protein kinase (AMPK), an intracellular energy sensor, in GHVD-causing cells. Alloreactive increased phosphorylation AMPK as early day 3 post-transplant (8-fold higher than naïve cells,...
Abstract The gut microbiome influences chronic inflammation of the airways via gut-lung axis. However, causal connections between microbes and their host, including underlying mechanisms for this phenomenon remain largely unknown. Here, we show that colonization with commensal protozoa, Tritrichomonas musculis ( T.mu ), remotely shapes lung immune landscape exacerbates allergic airway inflammation. We demonstrate T. mu mediates T B cell-dependent accumulation activation inflammatory group 2...
Abstract Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on host’s immune homeostasis, typically by elevating anti-microbial host defense. Tritrichomonas musculis ( T. mu ), protozoan gut commensal, strengthens defense against enteric Salmonella infections through Asc - and Il1r1 -dependent Th1 Th17 cell activation. However, underlying inflammasomes mediating this effect remain...
Abstract The colonic epithelium requires continuous renewal by intestinal stem cells (ISCs) to restore the barrier after damage and proliferation of epithelial is modulated dietary metabolites. We demonstrate that mice fed a high sugar diet failed repair damage, resulting in increased pathology. Culturing ISCs excess limited murine human colonoid development, indicating can directly affect proliferation. Similarly, vivo lineage tracing experiments transcriptomic analysis indicated impeded...
Due to increased incidence of whooping cough, further investigation the pathogenic mechanisms its causative agent, Bordetella pertussis, is medical importance. Previous in vitro assays indicate a correlation between elevated nicotinate concentrations and down‐regulation virulent toxins (e.g. pertussis toxin adenylate cyclase) B. pertussis. Furthermore, recent genomic analyses reveal unique degradation pathway This study analyzes effects disrupting gene that codes for 6‐hydroxynicotinate...