A5030194837- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- HIV Research and Treatment
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Cytomegalovirus and herpesvirus research
- Rabbits: Nutrition, Reproduction, Health
- Insect symbiosis and bacterial influences
- Reproductive Biology and Fertility
- Cytokine Signaling Pathways and Interactions
- Mosquito-borne diseases and control
- Nanowire Synthesis and Applications
- RNA and protein synthesis mechanisms
- Metabolism and Genetic Disorders
- Hormonal and reproductive studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Phytase and its Applications
- Proteins in Food Systems
- Hepatitis C virus research
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
Technical University of Munich
2019-2024
Institute for Advanced Study
2019-2024
Institute of Medical Microbiology and Hygiene
2020-2023
University of California, San Francisco
2015-2021
Innovative Genomics Institute
2016-2019
University of California, Berkeley
2016-2019
Universidad Católica de Santa Fe
2017
Hertie Institute for Clinical Brain Research
2016
Leibniz Institute for Zoo and Wildlife Research
2013-2014
Leibniz Association
2014
Significance T-cell genome engineering holds great promise for cancer immunotherapies and cell-based therapies HIV, primary immune deficiencies, autoimmune diseases, but genetic manipulation of human T cells has been inefficient. We achieved efficient editing by delivering Cas9 protein pre-assembled with guide RNAs. These active ribonucleoproteins (RNPs) enabled successful Cas9-mediated homology-directed repair in cells. RNPs provide a programmable tool to replace specific nucleotide...
Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize programmed cell death protein 1 [PD-1]) have both opened new avenues for cancer treatment, but the clinical potential of combined disruption inhibitory checkpoints CAR therapy remains incompletely explored. Here we show ligand (PD-L1) expression on tumor can render human (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired clearance a sub-cutaneous xenograft...
New genetic tools are needed to understand the functional interactions between HIV and human host factors in primary cells. We recently developed a method edit genome of CD4+ T cells by electroporation CRISPR/Cas9 ribonucleoproteins (RNPs). Here, we adapted this methodology high-throughput platform for efficient, arrayed editing candidate factors. CXCR4 or CCR5 knockout generated with resistant infection tropism-dependent manner, whereas LEDGF TNPO3 results tropism-independent reduction...
Distinct subsets of Tregs reside in nonlymphoid tissues where they mediate unique functions. To interrogate the biology tissue human health and disease, we phenotypically functionally compared healthy skin with those peripheral blood, inflamed psoriatic skin, metastatic melanoma. The mitochondrial enzyme, arginase 2 (ARG2), was preferentially expressed increased melanoma, reduced from skin. ARG2 enhanced Treg suppressive capacity vitro conferred a selective advantage for accumulation vivo....
Adoptive transfer of T cells expressing a transgenic cell receptor (TCR) has the potential to revolutionize immunotherapy infectious diseases and cancer. However, generation defined TCR-transgenic medicinal products with predictable in vivo function still poses major challenge limits broader more successful application this "living drug." Here, by studying 51 different TCRs, we show that conventional genetic engineering viral transduction leads variable TCR expression functionality as result...
Abstract Migrating lymphocytes acquire a polarized phenotype with leading and trailing edge, or uropod. Although in vitro experiments cell lines activated primary cultures have established that Rho-p160 coiled-coil kinase (ROCK)-myosin II-mediated uropod contractility is required for integrin de-adhesion on two-dimensional surfaces nuclear propulsion through narrow pores three-dimensional matrices, less known about the role of these two events during recirculation primary, nonactivated...
Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates different exhaustion states, is impacted by antiviral therapy, if metabolic checkpoints regulate dysfunction.Metabolic state, transcriptome of virus-specific CD8+ from HBV-infected (n=31) HCV-infected patients (n=52) were determined ex vivo during direct-acting (DAA) therapy. flux...
Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each member consists of an α β subunit together form composite cytokine. Within IL-12 family, IL-35 remains particularly ill-characterized on molecular level despite its key role autoimmune diseases cancer. Here we show both subunits, IL-12α EBI3, mutually promote their secretion from cells but not necessarily as...
ABSTRACT After encounter with central nervous system (CNS)- derived autoantigen, lymphocytes leave the lymph nodes and enter CNS. This event leads only rarely to subsequent tissue damage. Genes relevant in CNS- infiltrating cells leading CNS pathology are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG)- induced experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a chronic disease (CNS), resulting disability. To assess genes which...
DNA methylation is a heritable mechanism that acts in response to environmental changes, lifestyle and diseases by influencing gene expression eukaryotes. Epigenetic studies of wild organisms are mandatory understand their role e.g. adaptational processes the great variety ecological niches. However, strategies address those questions on methylome scale widely missing. In this study we present such strategy describe whole genome sequence analysis guinea pig. We generated full Wild pig (Cavia...
Abstract Immunotherapies with chimeric antigen receptor (CAR) T cells and checkpoint inhibitors (including antibodies that antagonize the programmed cell death protein 1 [PD-1] pathway) have both opened new avenues for cancer treatment, but clinical potential of combination blockade CAR therapy remains incompletely explored. Here we show ligand (PD-L1) expression on tumor can render human (anti-CD19 4-1BBζ) hypo-functional, resulting in impaired clearance a sub-cutaneous mouse xenograft...
Abstract Background Forkhead-Box-Protein P3 (FoxP3) is a transcription factor and marker of regulatory T cells, converting naive cells into Tregs that can downregulate the effector function other cells. We previously detected expression FoxP3 in retinal pigment epithelial (RPE) forming outer blood–retina barrier immune privileged eye. Methods investigated expression, subcellular localization, phosphorylation RPE vivo vitro after treatment with various stressors including age, laser burn,...
Rodents are the most abundant experimental nonhuman animals and commonly studied under standard laboratory housing conditions. As conditions affect animals' physiology behavior, this study investigated effects of indoor outdoor on body weight cortisol level wild cavies, Cavia aperea. The changing condition strongly influenced both parameters, which used as indicators for animal welfare. transfer from to enclosures resulted in a body-weight loss about 8%. In contrast, kept indoors showed...
Human T cells are central to physiological immune homeostasis, which protects us from pathogens without collateral autoimmune inflammation. They also the main effectors in most current cancer immunotherapy strategies 1 . Several decades of work have aimed genetically reprogram for therapeutic purposes 2–5 , but as human resistant standard methods large DNA insertion these approaches relied on recombinant viral vectors, do not target transgenes specific genomic sites 6, 7 In addition, need...