A5069861698- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Malaria Research and Control
- Mosquito-borne diseases and control
- CAR-T cell therapy research
- Immune Response and Inflammation
- Complement system in diseases
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Hematopoietic Stem Cell Transplantation
- Cancer, Stress, Anesthesia, and Immune Response
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- Neonatal Respiratory Health Research
- Monoclonal and Polyclonal Antibodies Research
- Blood groups and transfusion
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Telomeres, Telomerase, and Senescence
- Immune responses and vaccinations
- Hematological disorders and diagnostics
- Blood properties and coagulation
- Vagus Nerve Stimulation Research
University of Minnesota
2018-2024
Twin Cities Orthopedics
2024
Immunitas Therapeutics (United States)
2022-2024
University of Minnesota Medical Center
2019-2023
Mayo Clinic
2017-2018
WinnMed
2018
Albert Einstein College of Medicine
2012-2017
The COVID-19 pandemic has revealed the pronounced vulnerability of elderly and chronically ill to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced morbidity mortality. Cellular senescence contributes inflammation, multiple chronic diseases, age-related dysfunction, but effects on responses viral infection are unclear. Here, we demonstrate that senescent cells (SnCs) become hyper-inflammatory in response pathogen-associated molecular patterns (PAMPs), including SARS-CoV-2...
Microbial exposures can define an individual's basal immune state. Cohousing specific pathogen-free (SPF) mice with pet store mice, which harbor numerous infectious microbes, results in global changes to the system, including increased circulating phagocytes and elevated inflammatory cytokines. How these differences state influence acute response systemic infection is unclear. Cohoused exhibit enhanced protection from virulent Listeria monocytogenes (LM) infection, but morbidity mortality...
CD8 effector T cells with a CD127
Human cerebral malaria (HCM) is a serious complication of Plasmodium falciparum infection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, large-scale magnetic resonance imaging (MRI) study in humans identified brain swelling as the prominent predictor fatal HCM. Therefore, this study, we sought to define mechanism controlling edema through use murine experimental (ECM) model. Specifically, investigated ability CD8 T cells initiate...
The contribution of antigen-presenting cell (APC) types in generating CD8
Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of anemia (SCA) patients admitted with pain crisis, we evaluated the status molecules on neutrophils control IVIG-treated subjects pre- post-infusion up 800 mg/kg, same dose used murine studies. Mac-1 function significantly decreased from baseline low-dose IVIG (200-400 mg/kg) cohorts....
Abstract Conventional T cells are selected by peptide-MHC expressed cortical epithelial in the thymus, and not thymocytes themselves that do express MHC I or II. Instead, non-peptide presenting molecules like CD1d MR1, promote selection of PLZF + iNKT MAIT cells, respectively. Here, we report an inducible class-I transactivator mouse enables expression peptide different cell types. We show DP leads to expansion specific innate-like (PIL) cells. Akin PIL differentiate into three functional...
Abstract Microbial experience fundamentally shapes immunity, particularly during the perinatal period when immune system is underdeveloped, and novel microbial encounters are common. Most animal models raised in specific pathogen-free (SPF) conditions with relatively uniform communities. How SPF housing alter early-life development relative to natural exposure (NME) has not been thoroughly investigated. In this article, we compare SPF-raised mice born from immunologically experienced mothers...
Summary Spatial transcriptomics technologies enable the spatially resolved measurement of gene expression within a tissue specimen. With these technologies, researchers can investigate how cells organize into cellular niches which are defined as distinct regions in comprising specific composition cell types or phenotypes. While general-purpose software tools for exploratory analysis spatial data exist, there is need that specialize organization niches. This further enhance downstream...
Abstract Background: Intra-tumoral CD4+ and CD8+ T cells expressing inhibitory receptor CD161 have an effector memory phenotype with high cytotoxic potential. inhibits NK cell function in the presence of its ligand, CLEC2D. This suppression can be recovered by treatment IMT-009, a first class anti-CD161 antibody. Single transcriptomic analysis anti-PD1 refractory microsatellite stable colorectal tumors identified CD161+ PD1+ exhausted CD8 suggesting that may provide benefit these both as...
Abstract The elderly and those with chronic diseases face a 2 to 10-fold higher risk of hospitalization mortality post-infection compared healthy adults. Disease severity in the is often attributed aging immune system, including an expansion exhausted T cells that contribute inflammation have impaired activation function. It unclear how from aged individuals respond infection impact acute restoration cell produces functional excessive inflammation. In mouse model normal microbial exposure...
Abstract Cerebral malaria (CM) is one of the most lethal complications Plasmodium falciparum infection, responsible for a large fraction nearly 500,000 malaria-related deaths annually. In experimental mouse model CM (ECM), mice are inoculated with red blood cells infected berghei ANKA (PbA) parasites and develop CM-like disease within 6–10 days post-infection (dpi) resulting from CD8 T cell-mediated damage to CNS. We found that treatment C57Bl/6 interleukin (IL)-15 complexes (IL-15C; IL-15...
Abstract Physiological exposure to microbes profoundly effects the basal immune state, based on data from ‘dirty’ mice with a diverse microbial experience obtained after co-housing pet store mice. Most T cells in dirty and adult humans have an effector/memory phenotype, but specific pathogen free (SPF) or newborn few Ag-experienced memory cells. These differences prompted us define acute cytokine/chemokine response SPF co-housed inbred C57Bl/6 (B6) Co-housing for 60 d increased frequency of...
<h3>Background</h3> The CLEC2D/CD161 axis is a novel ligand-receptor pathway for immunotherapeutic intervention. IMT-009 monoclonal, aglycosylated human IgG1 antibody directed against CD161, C-type lectin-like receptor, which broadly expressed on NK cells and subsets of both CD4+ CD8+ T [Mathewson et al. 2021]. Its cognate ligand, CLEC2D (LLT1), the surface malignant immune cells, including activated B myeloid cells. <h3>Methods</h3> Functional inhibition CD161 by was demonstrated using...
Abstract Human cerebral malaria (HCM) is a serious lethal complication of Plasmodium falciparum infection. The most severe outcomes for patients include coma, permanent neurological deficits, and death. Recently, large-scale MRI study in humans identified brain swelling as the prominent indicator fatal HCM. In this study, we sought to define mechanism causing edema during by utilizing murine experimental model (ECM). We determined that areas blood-brain barrier (BBB) permeability colocalized...
Abstract Studies of the CD8 T cell memory compartment in mice have primarily been done young maintained specific pathogen free (SPF) environment. The murine is skewed towards central cells, whereas adult human cells are dominated by effector cells. akin to that neonate humans, suggesting there factors missing SPF required mature compartment. We wanted ask how exposure changes mice, so we utilized a model pet shop mouse co-housing (COH), which exposes wide variety normal pathogens. COH...
Abstract The elderly and those with chronic diseases have a 2 to 10-fold increased risk of hospitalization mortality following infection as compared healthy adults. A significant contributor disease severity is the aging immune system, including an expansion exhausted T cells. These cells simultaneously promote excessive levels inflammation display impaired cell activation function. How from aged individuals respond whether acute restoration further exacerbates inflammatory environment or...