Christine S. Falk
- Immune Cell Function and Interaction
- Transplantation: Methods and Outcomes
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Organ Transplantation Techniques and Outcomes
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Renal Transplantation Outcomes and Treatments
- Liver Disease Diagnosis and Treatment
- Hepatitis C virus research
- Hematopoietic Stem Cell Transplantation
- Hepatitis B Virus Studies
- Cancer Mechanisms and Therapy
- Liver Disease and Transplantation
- Cytomegalovirus and herpesvirus research
- Viral Infections and Immunology Research
- Polyomavirus and related diseases
- Liver physiology and pathology
- Immune cells in cancer
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- Reproductive System and Pregnancy
- Inflammatory mediators and NSAID effects
- Liver Diseases and Immunity
- PI3K/AKT/mTOR signaling in cancer
Medizinische Hochschule Hannover
2016-2025
German Center for Infection Research
2016-2025
German Center for Lung Research
2020-2025
National Center for Tumor Diseases
2006-2023
Heidelberg University
2006-2023
German Cancer Research Center
2009-2023
Straumann (Switzerland)
2023
Institute of Immunology
2015-2022
Tufts Medical Center
2021
Landscape Research Group
2021
There is pressing urgency to understand the pathogenesis of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme (ACE2), and in concert with host proteases, principally transmembrane serine protease (TMPRSS2), promotes cellular entry. The cell subsets targeted by tissues factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, mouse...
The marriage between immunology and cytometry is one of the most stable productive in recent history science. A rapid search PubMed shows that, as July 2017, using "flow immunology" a term yields more than 68 000 articles, first which, interestingly, not about lymphocytes. It might be stated after short engagement, exchange wedding rings officially occurred when idea to link fluorochromes monoclonal antibodies came about. After this, recognizing different types cells became relatively easy...
Immunoregulatory T cells of CD4+CD25+ phenotype suppress cell function and protect rodents from organ-specific autoimmune disease. The human counterpart this subset expresses high levels CD25 its role in disorders is currently under intense investigation. In multiple sclerosis (MS), a chronic inflammatory disease the central nervous system (CNS), activation circulating self-reactive with specificity for myelin components considered to be an important initiating event. Here, we investigated...
Abstract Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of myeloid in cancer patients and tumor-bearing mice that potently inhibits T cell responses. During tumor progression, MDSCs accumulate several organs, including the tissue. So far, tumor-infiltrating MDSC subpopulations remain poorly explored. In this study, we performed global gene expression profiling mouse granulocytic monocytic (MO-MDSC) subsets compared with from peripheral blood. RMA-S...
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations individual the variability present in population. Here we integrated Human Lung Cell Atlas (HLCA), combining 49 respiratory system into single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents consensus re-annotation with...
With about 350 million virus carriers, hepatitis B (HBV) infection remains a major health problem. HBV is noncytopathic causing persistent infection, but it still unknown whether host recognition of may activate an innate immune response. We describe that upon primary human liver cells, recognized by nonparenchymal cells the liver, mainly macrophages (Kupffer cells), although they are not infected. Within 3 hours, this leads to activation nuclear factor kappa (NF-kappaB) and subsequently...
Tumor microenvironment is characterized by chronic inflammation represented infiltrating leukocytes and soluble mediators, which lead to a local systemic immunosuppression associated with cancer progression. Here, we used the ret transgenic spontaneous murine melanoma model that mimics human melanoma. Skin tumors metastatic lymph nodes showed increased levels of inflammatory factors such as IL-1β, GM-CSF, IFN-γ, correlated tumor Moreover, Gr1 + CD11b myeloid-derived suppressor cells (MDSCs),...
Abstract Purpose: Tumor infiltrating T lymphocytes in colorectal cancer (CRC) have prognostic impact, but the role of natural killer (NK) cells CRC tissue is unclear. The contribution intratumoral cytokines and chemokines shaping composition inflammatory lymphocytic infiltrate also Experimental Design: In this study, localization densities NK within primary CRC, liver metastases, adenomas, normal tissues were analyzed on whole sections from 112 patients. a subset these patients, most...
Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses injury increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates aging augments immunogenicity. Ischemia reperfusion induces a systemic increase of cf-mt-DNA promotes dendritic cell-mediated, inflammatory responses. Comparable...
Abstract Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of is challenging since its cell populations are diverse be important even if scarce. To identify clinically relevant microenvironmental features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas normal control tissues. Our analyses revealed heterogeneous carcinoma...
•Restoration of HNF4A via mRNA delivery improves functions fibrotic primary hepatocytes from both mice and humans.•The encapsulated in lipid nanoparticles can be delivered into the liver.•Lipid nanoparticle-mediated ameliorates fibrosis cirrhosis different chronic liver injury models.•Paraoxonase 1, a therapeutic target HNF4A, contributes to anti-fibrotic effects HNF4A.•HNF4A affects macrophage infiltration polarization as well hepatic stellate cell activation. Background & AimsTherapeutic...
Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate citraconate similar properties. Here, we show that partially converted to intracellularly accumulation in macrophage activation depends on prior synthesis. When added human cells supraphysiological concentrations, all three reduce lactate levels, whereas strongest succinate dehydrogenase (SDH) inhibitor. In infected with...
ABSTRACT Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture variability present in population, these must include diverse demographics such as age ethnicity from both healthy diseased individuals. The growth size number single-cell datasets, combined with recent advances computational techniques, for first time makes it possible generate comprehensive large-scale through integration multiple datasets. Here, we integrated Human...
CD8(+) T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive lesions obtained within one year developing stage IV for recognition by cells.One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were T-cell infiltration. Melanoma cell lines established from respective characterized, determining T-cell-stimulatory capacity,...
Human in vitro generated monocyte-derived dendritic cells (moDCs) and macrophages are used clinically, e.g., to induce immunity against cancer. However, their physiological counterparts, ontogeny, transcriptional regulation, heterogeneity remains largely unknown, hampering clinical use. High-dimensional techniques were elucidate transcriptional, phenotypic, functional differences between human vivo mononuclear phagocytes facilitate full potential the clinic. We demonstrate that monocytes...
Objective— MicroRNAs (miRNA/miR) are stably present in body fluids and increasingly explored as disease biomarkers. Here, we investigated influence of impaired wound healing on the plasma miRNA signature their functional importance patients with type 2 diabetes mellitus. Approach Results— array profiling identified 41 miRNAs significantly deregulated diabetic controls when compared mellitus–associated peripheral arterial chronic wounds. Quantitative real-time polymerase chain reaction...
Persistent infection with hepatitis C virus (HCV) causes profound alterations of the cytokine and chemokine milieu in peripheral blood. However, it is unknown to what extend these affect progression liver disease whether HCV clearance normalizes soluble inflammatory mediators. We performed multianalyte profiling 50 plasma proteins 28 patients persistent advanced stages fibrosis or cirrhosis 20 controls fatty disease. The were treated for 24 weeks sofosbuvir ribavirin underwent sampling...
This prospective study investigated viral and host markers after stopping long-term therapy with nucleos(t)ide analogues in noncirrhotic patients hepatitis B e antigen-negative chronic B. After therapy, 13 of 15 experienced a virological relapse. Rebound virus DNA core-related antigen was associated induction plasma tumor necrosis factor, interleukin (IL) 10 , IL-12p70, CXCL10 subsequent decline surface (HBsAg), 20% HBsAg loss follow-up. The peak levels cessation were positively correlated...