A5052781798- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Cytomegalovirus and herpesvirus research
- Reproductive System and Pregnancy
- Monoclonal and Polyclonal Antibodies Research
- Diabetes and associated disorders
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Mast cells and histamine
- Ovarian cancer diagnosis and treatment
- Histone Deacetylase Inhibitors Research
- Diabetes Treatment and Management
- Synthesis and Biological Evaluation
- Galectins and Cancer Biology
- Chemokine receptors and signaling
- Neuroblastoma Research and Treatments
University of Minnesota
2016-2025
University of Minnesota System
2016-2024
Twin Cities Orthopedics
2022-2024
University of Minnesota Medical Center
2011-2023
Palmetto Hematology Oncology
2020-2022
Minnesota Oncology
2017-2021
Mayo Clinic in Arizona
2021
NHS Blood and Transplant
2021
Masonic Cancer Center
2011-2020
University of Massachusetts Chan Medical School
2006-2009
Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are potent regulators apoptosis, a process that is important for maintenance immune homeostasis. Recent evidence suggests TNFR-1 and Fas TRAIL receptors can also trigger an alternative form cell death morphologically distinct from apoptosis. Because molecular components including serine/threonine protein kinase receptor-interacting (RIP) required, we have referred to this as "programmed necrosis." We show TNFR-2 signaling...
Abstract Purpose: The effectiveness of NK cell infusions to induce leukemic remission is limited by lack both antigen specificity and in vivo expansion. To address the first issue, we previously generated a bispecific killer engager (BiKE) containing single-chain scFv against CD16 CD33 create an immunologic synapse between cells CD33+ myeloid targets. We have now incorporated novel modified human IL15 crosslinker, producing 161533 trispecific (TriKE) expansion, priming, survival, which...
NK cell-based immunotherapies have been gaining traction in the clinic for treatment of cancer. IL-15 is currently being used number clinical trials to improve cell expansion and function. The objective this study evaluate effect repetitive exposure on cells. An vitro model which human cells are continuously (on on) or intermittently off treated with was explore question. After treatment, were evaluated proliferation, survival, cycle gene expression, function, metabolic processes. Our data...
The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors, such as programmed cell death 1 (PD-1), or their ligands, PD-L1, has transformed the oncology landscape. However, durable tumor regression is limited to a minority patients. Therefore, combining immunotherapies with those receptors promising strategy bolster antitumor responses and improve response rates. Natural killer (NK) cells have potential augment inhibition therapies, PD-L1/PD-1...
MicroRNAs (miRs) have recently been identified as important regulators of gene expression at the posttranscriptional level. Although it has clearly established that miRs influence ontogeny several immune cell lineages, role individual during NK development not described. In this study, we show miR-181 levels a profound impact on human cells from CD34(+) hematopoietic progenitor and IFN-γ production in primary CD56(+) cells. We also demonstrate nemo-like kinase (NLK), an inhibitor Notch...
Natural killer (NK) cells with adaptive immunological properties expand and persist in response to human cytomegalovirus. Here, we explored the metabolic processes unique these cells. Adaptive CD3-CD56dimCD57+NKG2C+ NK exhibited hallmarks of lymphocyte memory, including increased oxidative mitochondrial respiration, membrane potential, spare respiratory capacity. Mechanistically, found that a short isoform chromatin-modifying transcriptional regulator, AT-rich interaction domain 5B (ARID5B),...
We improved the bispecific antibody platform that primarily engages natural killer (NK) cells to kill cancer through antibody-dependent cellular cytotoxicity (ADCC) by adding IL-15 as a crosslinker expands and self-sustains effector NK cell population. The overall goal was target B7-H3, an established marker predominantly expressed on minimally normal cells, prove it could in vitro inhibit tumor growth vivo. tri-specific engager (TriKETM) assembled DNA shuffling ligation using encoding...
Abstract Chronic lymphocytic leukemia (CLL) is characterized by chronic clonal expansion of mature CD19-expressing B lymphocytes and global dysfunction immune effectors, including natural killer (NK) cells. CLL remains incurable, novel approaches to refractory are needed. Our group has previously described trispecific engager (TriKE) molecules that redirect NK cell function against tumor TriKE reagents simultaneously bind an activating receptor on cells, CD16, a antigen while also providing...
Abstract Background Natural killer (NK) cells are non-antigen specific innate immune that can be redirected to targets of interest using multiple strategies, although none currently FDA-approved. We sought evaluate NK cell infiltration into tumors develop an improved understanding which histologies may most amenable cell-based therapies in the developmental pipeline. Methods DNA (targeted/whole-exome) and RNA (whole-transcriptome) sequencing was performed from 45 cancer types ( N = 90,916...
In conventional αβ T cells, the Tec family tyrosine kinase Itk is required for signaling downstream of cell receptor (TCR). also regulates development, lineage commitment, and effector function. A well established feature −/− mice their inability to generate helper type 2 (Th2) responses that produce IL-4, IL-5, IL-13; yet these have spontaneously elevated levels serum IgE increased numbers germinal center B cells. Here we show source this phenotype γδ as normal are observed in Tcrd mice....
Abstract The Tec kinases Itk and Rlk are required for efficient positive selection of conventional CD4+ CD8+ T cells in the thymus. In contrast, recent studies have shown that these dispensable development with characteristics innate cells. These findings raise questions about potential role NKT cell development, because represent a subset To address this issue, we examined invariant Itk−/− Itk/Rlk−/− mice. We find, as has been reported previously, mice reduced numbers predominantly immature...
Previously, we constructed a bispecific NK-cell-engager (BiKE) bearing single-chain variable fragments (scFv) against CD16 on NK cells and EpCAM tumor cells. This BiKE facilitated antigen-specific antibody-dependent cell-mediated cytotoxicity (ADCC) but did not induce cell expansion. We incorporated modified interleukin-15 cross-linker to create trispecific construct (TriKE) in order improve activation, proliferation, survival of Synthesis assembly hybrid genes encoding the TriKE was...