Axel Schambach
A5054362291- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Immune Cell Function and Interaction
- Viral Infectious Diseases and Gene Expression in Insects
- Acute Myeloid Leukemia Research
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Renal and related cancers
- RNA modifications and cancer
- Mesenchymal stem cell research
- Ubiquitin and proteasome pathways
- Advanced biosensing and bioanalysis techniques
- Cancer, Hypoxia, and Metabolism
- Blood disorders and treatments
- Immunodeficiency and Autoimmune Disorders
- Viral Infections and Immunology Research
- Hematopoietic Stem Cell Transplantation
- Lysosomal Storage Disorders Research
- HIV Research and Treatment
- RNA Research and Splicing
- Immune cells in cancer
- Animal Genetics and Reproduction
Medizinische Hochschule Hannover
2016-2025
Harvard University
2016-2025
Boston Children's Hospital
2016-2025
German Center for Infection Research
2023-2024
Hannover Re (Germany)
2020
Lund University
2019
Palmetto Hematology Oncology
2015
Dana-Farber Cancer Institute
2014
Center for Rheumatology
2013
Max Delbrück Center
2011-2012
For the aim of ex vivo engineering functional tissue substitutes, Laser-assisted BioPrinting (LaBP) is under investigation for arrangement living cells in predefined patterns. So far three-dimensional (3D) arrangements single or two-dimensional (2D) patterning different cell types have been presented. It has shown that are not harmed by printing procedure. We now demonstrate first time 3D vital LaBP as multicellular grafts analogous to native archetype and formation these cells. this...
Wiskott-Aldrich syndrome gene therapy is feasible, but γ-retroviral vectors contribute a substantial risk of leukemogenesis.
In previous clinical trials involving children with X-linked severe combined immunodeficiency (SCID-X1), a Moloney murine leukemia virus-based γ-retrovirus vector expressing interleukin-2 receptor γ-chain (γc) complementary DNA successfully restored immunity in most patients but resulted vector-induced through enhancer-mediated mutagenesis 25% of patients. We assessed the efficacy and safety self-inactivating retrovirus for treatment SCID-X1.
Gene transfer vectors may cause clonal imbalance and even malignant cell transformation by insertional upregulation of proto-oncogenes. Lentiviral (LV) with their preferred integration in transcribed genes are considered less genotoxic than gammaretroviral (GV) preference for next to transcriptional start sites regulatory gene regions. Using a sensitive culture assay series self-inactivating (SIN) vectors, we found that the lentiviral insertion pattern was approximately threefold likely...
Recent studies highlighted long noncoding RNAs (lncRNAs) to play an important role in cardiac development. However, understanding of lncRNAs diseases is still limited. Global lncRNA expression profiling indicated that several transcripts are deregulated during pressure overload-induced hypertrophy mice. Using stringent selection criteria, we identified Chast (cardiac hypertrophy-associated transcript) as a potential candidate influences cardiomyocyte hypertrophy. Cell fractionation...
Checkpoints that limit stem cell self-renewal in response to DNA damage can contribute cancer protection but may also promote tissue aging. Molecular components control responses remain be delineated. Using vivo RNAi screens, we identified basic leucine zipper transcription factor, ATF-like (BATF) as a major component limiting of hematopoietic cells (HSCs) telomere dysfunction and γ-irradiation. induces BATF G-CSF/STAT3-dependent manner resulting lymphoid differentiation HSCs. deletion...
Genome editing with the CRISPR-Cas9 system has enabled unprecedented efficacy for reverse genetics and gene correction approaches. While off-target effects have been successfully tackled, effort to eliminate variability in sgRNA efficacies-which affect experimental sensitivity-is its infancy. To address this issue, studies analyzed molecular features of highly active sgRNAs, but independent cross-validation is lacking. Utilizing fluorescent reporter knock-out assays verification at selected...
Induced pluripotent stem cells (iPSCs) can be derived from somatic by gene transfer of reprogramming transcription factors. Expression levels these factors strongly influence the overall efficacy to form iPSC colonies, but additional contribution stochastic cell-intrinsic has been proposed. Here, we present engineered color-coded lentiviral vectors in which codon-optimized are co-expressed a strong retroviral promoter that is rapidly silenced iPSC, and imaged conversion fibroblasts iPSC. We...
Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology understand the biology of myelin diseases develop treatments for such disorders. Here, we demonstrate that induction three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor is sufficient rapidly O4+ OL with an efficiency up 70% 28 d global gene-expression profile comparable primary OL. We further...
Interleukin-3 (IL-3) is capable of supporting the proliferation a broad range hematopoietic cell types, whereas granulocyte colonystimulating factor (G-CSF) and macrophage CSF (M-CSF) represent critical cytokines in myeloid differentiation.When this was investigated pluripotent-stem-cell-based differentiation model, IL-3/G-CSF or IL-3/M-CSF exposure resulted continuous generation cells from an intermediate myeloid-cell-forming complex containing CD34 + clonogenic progenitor for more than 2...
Primary immunodeficiencies (PIDs) represent exquisite models for studying mechanisms of human host defense. In this study, we report on two unrelated kindreds, with patients each, who had cryptosporidial infections associated chronic cholangitis and liver disease. Using exome candidate gene sequencing, identified distinct homozygous loss-of-function mutations in the interleukin-21 receptor (IL21R; c.G602T, p.Arg201Leu c.240_245delCTGCCA, p.C81_H82del). The IL-21RArg201Leu mutation causes...
Background Combined immunodeficiencies are marked by inborn errors of T-cell immunity in which the T cells that present quantitatively or functionally deficient. Impaired humoral is also common. Patients have severe infections, autoimmunity, both. The specific molecular, cellular, and clinical features many types combined remain unknown. Methods We performed genetic cellular immunologic studies involving five unrelated children with early-onset invasive bacterial viral lymphopenia, defective...
Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent β-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor transduced with the BB305 lentiviral vector encoding β-globin (βA-T87Q) gene.In this open-label, phase 3 study, we evaluated efficacy safety of beti-cel in adult pediatric patients a non-β0/β0 genotype. Patients underwent myeloablation busulfan (with doses adjusted on basis pharmacokinetic analysis) received intravenously. The primary end...
•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...
Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options. In this study, we focus on the properties of airway basal cells (ABC) obtained from patients IPF (IPF-ABC). Single cell RNA sequencing (scRNAseq) bronchial brushes revealed extensive reprogramming IPF-ABC towards KRT17 high PTEN low dedifferentiated type. 3D organoid model, compared to ABC healthy volunteers, give rise more bronchospheres, de novo structures resembling lung developmental...