A5064517124- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- AI in cancer detection
- Computational Drug Discovery Methods
- Biosimilars and Bioanalytical Methods
- Multiple Myeloma Research and Treatments
- Immune cells in cancer
- Digital Imaging for Blood Diseases
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Nanoplatforms for cancer theranostics
- Dermatology and Skin Diseases
- Advanced Biosensing Techniques and Applications
- Protein Degradation and Inhibitors
- Psoriasis: Treatment and Pathogenesis
- Gene Regulatory Network Analysis
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Biochemical and Structural Characterization
- Advanced Proteomics Techniques and Applications
- Antimicrobial Peptides and Activities
- Artificial Immune Systems Applications
- Contact Dermatitis and Allergies
- bioluminescence and chemiluminescence research
- Phagocytosis and Immune Regulation
ETH Zurich
2019-2024
SIB Swiss Institute of Bioinformatics
2023
Institute of Medical Microbiology and Hygiene
2014
University of Tübingen
2014
The human immune system is composed of a distributed network cells circulating throughout the body, which must dynamically form physical associations and communicate using interactions between their cell-surface proteomes
Abstract Phagocytosis is a process in which target cells or particles are engulfed and taken up by other cells, typically professional phagocytes; this crucial many physiological processes disease states. The detection of targets for phagocytosis directed complex repertoire cell surface receptors. Pattern recognition receptors directly detect binding uptake, while opsonic complement objects coated soluble factors. However, the importance single combinatorial marker expression across...
Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible are still not well understood and involve several factors on the host bacterial side. One key cell wall teichoic acid (WTA) of aureus, which governs direct interactions with nasal epithelial surfaces. We report here first receptor glycopolymer WTA cells. In assay systems this type F-scavenger receptor, termed SREC-I, bound in charge dependent manner mediated adhesion to cells vitro. impact SREC-I...
The molecular nanoscale organization of the surfaceome is a fundamental regulator cellular signaling in health and disease. Technologies for mapping spatial relationships cell surface receptors their extracellular synapses would unlock theranostic opportunities to target protein communities possibility engineer signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables targeted elucidation acute interactions on between living cells using light-controlled singlet...
Abstract Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite growing arsenal of approved therapies, MM remains incurable in need guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug immunotherapy sensitivities across 101 bone marrow samples from 70 patients with using multiplexed immunofluorescence, automated microscopy deep-learning-based single-cell phenotyping. Combined...
After antigen stimulation, naïve T cells display reproducible population-level responses, which arise from individual pursuing specific differentiation trajectories. However, cell-intrinsic predeterminants controlling these single-cell decisions remain enigmatic. We found that the subcellular architectures of CD8 cells, defined by presence (T
Phenotypic plasticity is essential to the immune system, yet factors that shape it are not fully understood. Here, we comprehensively analyze cell phenotypes including morphology across human cohorts by single-round multiplexed immunofluorescence, automated microscopy, and deep learning. Using uncertainty of convolutional neural networks cluster eight distinct subsets, find resulting maps influenced donor age, gender, blood pressure, revealing polarization activation-associated classes. We...
Myelofibrosis is a hematopoietic stem cell disorder belonging to the myeloproliferative neoplasms. patients frequently carry driver mutations in either JAK2 or Calreticulin (CALR) and have limited therapeutic options. Here, we integrate ex vivo drug response proteotype analyses across myelofibrosis patient cohorts discover targetable vulnerabilities associated strategies. Drug sensitivities of mutated progenitor cells were measured blood using high-content imaging single-cell deep...
Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease with poorly understood pathogenesis. Through molecularly driven precision medicine approach and an extensive mechanistic pathway analysis in PRP samples, compared to psoriasis, atopic dermatitis, healed PRP, healthy controls, we identified IL-1β as key mediator, orchestrating NF-κB-mediated IL-1β-CCL20 axis, including activation of CARD14 NOD2. Treatment three patients the IL-1 antagonists anakinra canakinumab resulted rapid...
Abstract Drug testing in patient biopsy-derived cells can identify potent treatments for patients suffering from relapsed or refractory hematologic cancers. Here we investigate the use of weakly supervised deep learning on cell morphologies (DML) to complement diagnostic marker-based identification malignant and nonmalignant drug testing. Across 390 biopsies 289 with diverse blood cancers, DML-based responses show improved reproducibility clustering drugs same mode action. DML does so by...
Abstract Elderly or unfit patients with relapsed acute myeloid leukemia (AML) face a poor prognosis and are likely to rapidly exhaust all registered treatment options. Pharmacoscopy, an image-based ex vivo drug screening platform, has previously been suggested as tool for selection in AML. We used pharmacoscopy generate personalized recommendations 30 relapse settings of 24 AML which exhausted standard therapeutic evaluated whether can be employed within the narrow timeframe available under...
Acute myeloid leukemia (AML) is characterized by malignant precursors that span a cellular hierarchy from dedifferentiated leukemic stem cells to mature blasts. While the diagnostic and prognostic importance of AML blast maturation increasingly recognized, personalized therapies are currently not tailored patients individual makeup this hierarchy. In study, we use multiplexed image-based ex vivo drug screening (pharmacoscopy) systematically quantify sensitivity across patients. We analyzed...
Abstract Delineating the molecular nanoscale organization of surfaceome is pre-requisite for understanding cellular signaling. Technologies mapping spatial relationships cell surface receptors and their extracellular signaling synapses would open up theranostic opportunities possibility to engineer Here, we developed an optoproteomic technology termed LUX-MS that exploits singlet oxygen generators (SOG) light-triggered identification acute protein interactions on living cells. Using...
Summary Phenotypic plasticity is essential to the immune system, yet factors that shape it are not fully understood. Here, we comprehensively analyze cell phenotypes including morphology across human cohorts by single-round multiplexed immunofluorescence, automated microscopy, and deep learning. Using uncertainty of convolutional neural networks cluster 8 distinct subsets, find resulting maps influenced donor age, gender, blood pressure, revealing polarization activation-associated classes....
Supplementary Figure from Deep Morphology Learning Enhances <i>Ex Vivo</i> Drug Profiling-Based Precision Medicine
Supplementary Data from Deep Morphology Learning Enhances <i>Ex Vivo</i> Drug Profiling-Based Precision Medicine
Supplementary Figure from Deep Morphology Learning Enhances <i>Ex Vivo</i> Drug Profiling-Based Precision Medicine
Supplementary Data from Deep Morphology Learning Enhances <i>Ex Vivo</i> Drug Profiling-Based Precision Medicine
<div>Abstract<p>Drug testing in patient biopsy-derived cells can identify potent treatments for patients suffering from relapsed or refractory hematologic cancers. Here we investigate the use of weakly supervised deep learning on cell morphologies (DML) to complement diagnostic marker-based identification malignant and nonmalignant drug testing. Across 390 biopsies 289 with diverse blood cancers, DML-based responses show improved reproducibility clustering drugs same mode action....
<div>Abstract<p>Drug testing in patient biopsy-derived cells can identify potent treatments for patients suffering from relapsed or refractory hematologic cancers. Here we investigate the use of weakly supervised deep learning on cell morphologies (DML) to complement diagnostic marker-based identification malignant and nonmalignant drug testing. Across 390 biopsies 289 with diverse blood cancers, DML-based responses show improved reproducibility clustering drugs same mode action....
Abstract Pityriasis rubra pilaris (PRP) is a rare inflammatory skin disease which lacks efficacious standard-of-care treatments. Molecular studies of lesions revealed that IL-1β central to the pathogenesis PRP. Treatment three patients with IL-1-targeting biologics anakinra and canakinumab resulted in rapid clinical improvement reversal PRP-associated molecular signature. We identified an NF-κB-mediated IL-1β-CCL20 axis response Our results reveal role signaling PRP highlights its prominence...