A5088152896- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Multiple Myeloma Research and Treatments
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Chemokine receptors and signaling
- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Renal Transplantation Outcomes and Treatments
- Biomedical Ethics and Regulation
- Cytomegalovirus and herpesvirus research
- Gut microbiota and health
- Bioactive Compounds and Antitumor Agents
- Renal function and acid-base balance
- Climate Change and Health Impacts
- Autophagy in Disease and Therapy
- Protein Degradation and Inhibitors
- Tracheal and airway disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer therapeutics and mechanisms
- Thermal Regulation in Medicine
- Vasculitis and related conditions
- Nutrition, Genetics, and Disease
Fred Hutch Cancer Center
2021-2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2023
Cancer Research Center
2023
Allina Health
2022
VA Puget Sound Health Care System
2021-2022
Innsbruck Medical University
2021
Universität Innsbruck
2021
University of Washington
2021
Seattle University
2020
University of Bonn
2019
Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (T PHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression DNA accessibility revealed that genes encoding these functional proteins correlated with BATF motif accessibility. IFN-γ + effectively killed myeloma comparable efficacy transitory effectors, disease...
Calcineurin inhibitors (CNIs) constitute the backbone of modern acute graft-versus-host disease (aGVHD) prophylaxis regimens but have limited efficacy in prevention and treatment chronic GVHD (cGVHD). We investigated effect CNIs on immune tolerance after stem cell transplantation with discovery-based single-cell gene expression T receptor (TCR) assays clonal immunity tandem traditional protein-based approaches preclinical modeling. While cyclosporin tacrolimus suppressed expansion CD8+ cells...
Steroids are commonly administered for the control of edema, mass effect, and side effects from therapy to patients with malignant glioma who receiving radiotherapy chemotherapy. Here, we report that therapeutic concentrations dexamethasone (DEX) attenuate cytotoxicity growth inhibition human cells induced by exposure several chemotherapeutics, including ACNU, VM-26, vincristine, cytarabine, metho-trexate, adriamycin. DEX-mediated cytoprotection is not linked DEX on cell proliferation....
β-lapachone and camptothecin are structurally unrelated agents thought to inhibit topoisomerase-I activity through distinct mechanisms. We find that is much more potent than in inducing acute cytotoxic effects on human malignant glioma cells. Acute cytotoxicity induced by both drugs apoptotic electron microscopy, but not blocked inhibitors of RNA or protein synthesis associated with changes the expression bcl-2, bax, p53, p21 GADD45 proteins. In contrast, prolonged exposure cells for 72 hr...
Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up investigate the role of candidate genes in susceptibility patients younger than 51 years at diagnosis. 246 with primary, histologically or cytologically confirmed neoplasm, recruited from 2000 2003 major clinics across Germany, were matched 223 unrelated healthy controls. 11 single nucleotide polymorphisms reported associations have been genotyped. Genetic gene-smoking...
Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation BMT, we found antiviral humoral induced by IL-6 signaling. signaling in T cells maintained Th1 cells, resulting sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss the neonatal Fc receptor (FcRn) responsible for IgG recycling, rapid loss. cell-specific...
The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic flow while allowing adrenaline-associated vasculature to be assessed at different mean arterial pressure (MAP) levels independently the flow.After eight minutes cardiac arrest, low-flow life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous administration...
Some hematological malignancies such as multiple myeloma are inherently resistant to immune-mediated antitumor responses, the cause of which remains unknown. Allogeneic bone marrow transplantation (alloBMT) is only curative immunotherapy for due profound graft-versus-tumor (GVT) effects, but relapse major death. We developed murine models alloBMT where malignancy either sensitive [acute myeloid leukemia (AML)] or (myeloma) GVT effects. found that CD8
A significant number of ovarian borderline tumors (BOTs) and metastatic nonovarian primaries are erroneously diagnosed as carcinomas. If BOTs misdiagnosed cancer, patients may not only experience nonbeneficial morbidity but have to cope with an incorrect diagnosis cancer for the rest their lives. In cases disease mistaken primary, more adequate therapeutic modalities be withheld from some patients. Finally, clinical trials biased through unintended disregard histological inclusion...
Autologous stem cell transplantation (ASCT) with subsequent lenalidomide maintenance is standard consolidation therapy for multiple myeloma, and a subset of patients achieve durable progression-free survival that suggestive long-term immune control. Nonetheless, most ultimately relapse, suggesting escape. TIGIT appears to be potent inhibitor myeloma-specific immunity represents promising new checkpoint target. Here we demonstrate high expression on activated CD8+ T cells in mobilized...
Autologous stem cell transplantation (ASCT) is the standard of care consolidation therapy for eligible patients with myeloma but most eventually progress, an event associated features immune escape. Novel approaches to enhance antimyeloma immunity after ASCT represent a major unmet need. Here, we demonstrate that patient-mobilized grafts contain high numbers effector CD8 T cells and immunosuppressive regulatory (Tregs). We showed bone marrow (BM)-residing are efficiently mobilized during...
The polymorphism SNP309 (rs2279744) in the promoter region of MDM2 gene has been shown to alter protein expression and may play a role susceptibility lung cancer. is key inhibitor p53 several mechanisms MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth apoptosis. We used 635 Caucasian patients diagnosed with cancer before 51 years age 1300 healthy gender frequency matched population controls investigate association between risk developing early...
Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality Western Germany.Children aged 2 months 17 years.In a multi-center retrospective of 20 children's hospitals were obtained analyzed by chart review. Risk identified assessed multivariate regression analysis.Overall 83 cases was 25% (21 patients). Significant high PRISM III score, low pH, arterial systolic blood pressure, presence...
Treatment of heart failure with the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan improved glycemic control in individuals type 2 diabetes. The relative contribution neprilysin inhibition versus II receptor antagonism to this benefit remains unknown. Thus, we sought determine effects sacubitril blocker valsartan on beta-cell function and glucose homeostasis a mouse model reduced first-phase insulin secretion, whether any beneficial are additive/synergistic when combined...
Objective To determine outcomes in hospitalised patients with sepsis and reported penicillin allergy (PcnA). Design Observational retrospective cohort study using data from electronic health records. Setting A large single system 11 hospitals of small, medium sizes including a 630-bed tertiary care teaching hospital. Participants Patients (n=5238) ≥18 years age, sepsis, severe or septic shock between 1 January 2016 31 December 2018, received antibacterial agents, had documented PcnA status....
Abstract IL-10 producing CD4 +type-1 regulatory T cells (Tr1) mediate immune tolerance during chronic infection, autoimmunity, and transplantation. We previously demonstrated that eomesodermin (Eomes) promotes Tr1 cell (Eomes +IL-10 +) development after allogenic bone marrow transplantation (alloBMT). Here we define the differentiation trajectory of functional states therein. Eomes −IL-10 −, −and +subsets (defined by mCherry GFP expression respectively) were FACS sorted alloBMT transferred...
Apoptosis repressor with caspase recruitment domain (ARC) is an endogenous inhibitor of cell death signaling that expressed in insulin-producing β cells. ARC has been shown to reduce β-cell response diabetogenic stimuli vitro, but its role maintaining glucose homeostasis vivo not fully established. Here we examined whether loss FVB background mice exacerbates high fat diet (HFD)-induced hyperglycemia over 24 weeks. Prior commencing 24-week HFD, ARC-/- had lower body weight than wild type...