A5018265015- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Reproductive System and Pregnancy
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- HIV Research and Treatment
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- Silymarin and Mushroom Poisoning
- Monoclonal and Polyclonal Antibodies Research
- Malaria Research and Control
- Immune Response and Inflammation
- HIV/AIDS Research and Interventions
- HIV/AIDS drug development and treatment
- Pregnancy and preeclampsia studies
- Pregnancy and Medication Impact
- IL-33, ST2, and ILC Pathways
- Virus-based gene therapy research
- Drug-Induced Hepatotoxicity and Protection
- COVID-19 Impact on Reproduction
- vaccines and immunoinformatics approaches
- Urinary Tract Infections Management
- Hepatitis C virus research
- Cancer Immunotherapy and Biomarkers
University of Minnesota
2022-2025
Fred Hutch Cancer Center
2012-2024
University of Washington
2017-2024
University of Minnesota Medical Center
2023-2024
Cancer Research Center
2017-2021
Seattle University
2019
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2016-2017
University Hospital Bonn
2014
Seattle Pacific University
2012
Abstract Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain 1,2 . An inherent weakness current approaches is that therapeutically targeted pathways are not restricted to tumours, also found other tissue microenvironments, complicating 3,4 Despite great efforts define inflammatory processes tumour microenvironment, understanding tumour-unique immune alterations limited by a knowledge gap regarding cell populations inflamed human tissues....
Abstract Bystander activation of memory T cells occurs in the absence cognate antigen during infections that elicit strong systemic inflammatory responses, which subsequently affect host immune responses. Here we report cell bystander is not limited to induction by inflammation. We initially observe potential a cohort human vaccine recipients. Using mouse model system, then find CD8 + are specifically recruited sites with activated antigen-presenting (APCs) CXCR3-dependent manner. In...
Abstract Animal model studies highlight the role of innate-like lymphocyte populations in early inflammatory response and subsequent parasite control following Plasmodium infection. IFN-γ production by these lymphocytes likely plays a key disease severity. Analyzing human T cell NK responses infection with has been challenging because stages are clinically silent. To overcome this limitation, we examined blood samples from controlled malaria (CHMI) study Tanzanian cohort, which volunteers...
T cell receptor (TCR) stimulation leads to the expression of transcription factor thymocyte selection–associated high-mobility group box (TOX). Prolonged TCR signaling, such as encountered during chronic infections or in tumors, sustained TOX expression, which is required for induction a state exhaustion dysfunction. Although CD8+ memory (Tmem) cells mice typically do not express at steady state, some human Tmem but appear fully functional. This seeming discrepancy between mouse and has led...
Abstract Agonistic anti-CD40 with anti-PD-1 can elicit objective responses in a small number of patients pancreatic ductal adenocarcinoma (PDA). Better understanding their individual effects on the PDA tumor microenvironment will help inform new strategies to further improve outcomes. Herein, we map tumor-specific CD8+ T-cell differentiation following agonistic and/or anti-PDL1 PDA. Rare Tcf1+Slamf6+ T cells (TSTEM) are shown seed memory precursors that transition into continuum exhausted...
Purified silymarin-derived natural products from the milk thistle plant (Silybum marianum) block hepatitis C virus (HCV) infection and inhibit T cell proliferation in vitro. An intravenous formulation of silibinin (SIL), a major component silymarin, displays anti-HCV effects humans also inhibits T-cell We show that SIL inhibited replication HIV-1 TZM-bl cells, PBMCs, CEM cells suppression coincided with dose-dependent reductions actively proliferating CD19+, CD4+, CD8+ resulting fewer CD4+...
Interleukin-15 (IL-15) is often considered a central regulator of memory CD8+ T cells, based primarily on studies recirculating subsets. However, recent work identified IL-15-independent cell populations, including tissue-resident cells (TRM) in some nonlymphoid tissues (NLTs). Whether this reflects the existence IL-15-insensitive unclear. We report that IL-15 complexes (IL-15c) stimulate rapid proliferation and expansion both circulating subsets across lymphoid with varying magnitude by...
Abstract Mucosal-associated invariant T (MAIT) cells acquire effector function in response to proinflammatory signals, which synergize with TCR-mediated signals. We asked if cell-intrinsic regulatory mechanisms exist curtail MAIT cell akin the activation-induced expression of inhibitory receptors by conventional cells. examined human from blood and oral mucosal tissues RNA sequencing found differential immunoregulatory genes, including CTLA-4, isolated tissue. Using an ex vivo experimental...
Silymarin (SM), and its flavonolignan components, alter cellular metabolism inhibit inflammatory status in human liver T cell lines. In this study, we hypothesized that SM suppresses both acute chronic immune activation (CIA), including the context of HIV infection. treatment suppressed expression exhaustion markers on CD4+ CD8+ cells from chronically-infected, HIV-positive subjects. also showed a trend towards modifying memory subsets HIV+ HIV-negative setting, trends suppressing...
Abstract Background Nonhuman primates ( NHP s) are an important model organism for studies of HIV pathogenesis and preclinical evaluation anti‐ therapies. The successful translation ‐derived data to clinically relevant will require better understanding the viral strains species used their responses existing antiretroviral therapies ART ). Methods Five pigtailed macaques M acaca nemestrina ) were productively infected with SIV/HIV chimeric virus SHIV‐1157 ipd3N4 following intravenous...
SUMMARY Interleukin-7 (IL-7) is considered a critical regulator of memory CD8 + T cell homeostasis, but this primarily based on analysis circulating and not tissue-resident (T RM ) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during homeostasis has been directly tested. Using inducible deletion, we found that Il7ra loss had only modest effect persistence subsets IL-7Rα was required normal basal proliferation. Loss IL-15 imposed heightened dependence cells,...
The ninth author's name was spelled incorrectly. correct is: Leonidas Stamatatos. Additionally, the spelling of individual who provided SIL, mentioned in SIL section Methods, is Ralf Torsten-Pohl.
We redesigned residues on the surface of MICA, a protein that binds homodimeric immunoreceptor NKG2D, to increase binding affinity with series rational, incremental changes. A fixed-backbone RosettaDesign protocol scored set initial mutations, which we tested by plasmon resonance for thermodynamics and kinetics NKG2D binding, both singly in combination. combined best four mutations at three affinity-enhancing below interface found previous design strategy. After curating scores...
Placentation presents immune conflict between mother and fetus, yet in normal pregnancy maternal immunity against infection is maintained without expense to fetal tolerance. This believed result from adaptations at the maternal-fetal interface (MFI) which affect T cell programming, but identities (i.e., memory subsets antigenic specificities) of cells signals that mediate fates functions MFI remain poorly understood. We found intact recruitment programs as well pro-inflammatory cytokine...
Memory CD8 T cells (T
Abstract T cell receptor (TCR) stimulation leads to expression of the transcription factor TOX. Prolonged TCR signaling, such as encountered during chronic infections or in tumors, sustained TOX expression, which induces a state exhaustion dysfunction. While CD8 memory cells (T mem ) specific pathogen-free laboratory mice typically do not express TOX, functional human show heterogeneous levels. Whether TCR-independent mechanisms can alter and murine has been defined. We report that mouse...
Abstract Innate and adaptive immune responses are typically considered to occur sequentially following an infection. The innate system responds initially infection the antigen-specific T B cell response develops subsequently. Although peak of lags days behind response, inflammatory signals lead rapid expression Granzyme Interferon-γ in memory CD8+ cells. This occurs a receptor (TCR) independent manner is referred as “bystander activation.” We others have demonstrated that these...
Abstract Memory CD8+ T lymphocytes are typically considered to contribute host immunity when they reencounter their specific antigen; however, in the absence of cognate antigen, inflammatory signals can elicit rapid expression Granzyme B and Interferon-γ memory cells. This is referred as “bystander activation” occurs during early stages infection, which dominated by innate immune responses. We others have demonstrated that bystander-activated cytotoxic (BA-CTL) kill target cells an...