A5062065019- Melanoma and MAPK Pathways
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Synthesis and biological activity
- Immune Cell Function and Interaction
- Cutaneous Melanoma Detection and Management
- interferon and immune responses
- Biochemical and Molecular Research
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Protein Kinase Regulation and GTPase Signaling
- Mathematical Biology Tumor Growth
- Neuroblastoma Research and Treatments
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Phagocytosis and Immune Regulation
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
Columbia University
2023-2025
Columbia University Irving Medical Center
2019-2025
University Hospital Magdeburg
2017-2021
Harvard University
2019-2020
Center for Systems Biology
2019-2020
University of Bonn
2012-2017
University Hospital Bonn
2016
Abstract We propose an extension of a standard stochastic individual-based model in population dynamics which broadens the range biological applications. Our primary motivation is modelling immunotherapy malignant tumours. In this context different actors, T-cells, cytokines or cancer cells, are modelled as single particles (individuals) system. The main expansions distinguishing cells by phenotype and genotype, including environment-dependent phenotypic plasticity that does not affect...
Abstract We previously reported the results of a randomized phase II trial (NCT02904954) in patients with early-stage non-small cell lung cancer (NSCLC) who were treated either two preoperative cycles anti-PD-L1 antibody durvalumab alone or combined immunomodulatory doses stereotactic radiation (DRT). The met its primary endpoint major pathological response, which was significantly higher following DRT no new safety signals. Here, we report on prespecified secondary disease-free survival...
Human melanomas exhibit considerable genetic, pathologic, and microenvironmental heterogeneity. Genetically engineered mice have successfully been used to model the genomic aberrations contributing melanoma pathogenesis, but their ability recapitulate phenotypic variability of human disease complex interactions with immune system not addressed. Here, we report unexpected finding that cell-poor pigmented cell-rich amelanotic developed simultaneously in Cdk4R24C-mutant upon melanocyte-specific...
Patients with melanoma resistant to RAF/MEK inhibitors (RMi) are frequently other therapies, such as immune checkpoint (ICI), and individuals succumb their disease. New drugs that control tumor growth favorably modulate the environment therefore needed. We report small-molecule CX-6258 has potent activity against both RMi-sensitive (RMS) -resistant (RMR) cell lines. Haspin kinase (HASPIN) was identified a target of CX-6258. HASPIN inhibition resulted in reduced proliferation, frequent...
Current methods for biomarker discovery and target identification in immuno-oncology rely on static snapshots of tumor immunity. To thoroughly characterize the temporal nature antitumor immune responses, we developed a 34-parameter spectral flow cytometry panel performed high-throughput analyses critical contexts. We leveraged two distinct preclinical models that recapitulate cancer immunoediting (NPK-C1) checkpoint blockade (ICB) response (MC38), respectively, profiled multiple relevant...
ABSTRACT The cell autonomous balance of immune-inhibitory and -stimulatory signals is a critical yet poorly understood process in cancer immune evasion. Using patient-derived co-culture models humanized mouse models, we show that an intact CD58:CD2 interaction necessary for anti-tumor immunity. Defects this axis lead to multi-faceted evasion through impaired CD2-dependent T polyfunctionality, exclusion, intra-tumoral proliferation, concurrent protein stabilization PD-L1. We performed...
Abstract Most melanoma‐associated deaths result from the early development of metastasis. Toll‐like receptor 4 (TLR4) expression on nontumor cells is well known to contribute tumor and metastatic progression. The role TLR4 however less understood. Here we describe as a driver progression spread melanoma by employing transplantable mouse model. HCmel12 lacking functional showed increased sensitivity necrosis factor α induced cell killing in vitro compared with intact TLR4. Interestingly,...
Type I interferons are evolutionally conserved cytokines, with broad antimicrobial and immunoregulatory functions. Despite well-characterised role in spontaneous cancer immunosurveillance, the function of type IFNs immunotherapy remains incompletely understood.We utilised genetic mouse models to explore IFN system CD8+ T-cell targeting melanocytic lineage antigen gp100.The therapeutic efficacy adoptively transferred T cells was found depend on a functional myeloid immune cells. Compromised...
Abstract Resistance to immune checkpoint inhibitors (ICI) that activate T cell mediated anti-tumor immunity is a key challenge in cancer therapy, yet the underlying mechanisms remain poorly understood. To further elucidate those, we developed new approach, Perturb-CITE-seq, for pooled CRISPR perturbation screens with multi-modal RNA and protein single-cell profiling readout applied it screen patient-derived autologous melanoma tumor infiltrating lymphocyte (TIL) co-cultures. We profiled 20...
Immunotherapies have shown significant promise as an impactful strategy in cancer treatment. However, glioblastoma multiforme (GBM), the most prevalent primary brain tumor adults, these therapies demonstrated lower efficacy than initially anticipated. Consequently, there is urgent need for strategies to enhance effectiveness of immune treatments. AURKA has been identified a potential drug target GBM An analysis cell transcriptome following inhibition revealed influence on system. Our...
Abstract The activation of STING (stimulator interferon genes) has been widely shown to induce signaling pathways, triggering type I and ultimately generating anti-tumor immunity. Whereas initial preclinical studies on agonists exhibited boost in response, clinical trials combining agonist immune checkpoint blockade agent PD-1 reported that only small subset patients benefited from the treatment. This study highlights a potential key mechanism underlying lack benefit observed most trial...