I am a physicist working in systems and precision medicine applied to cancer and autoimmune diseases. I lead an interdisciplinary team that combines computational modeling, bioinformatics, multi-criteria decision algorithms, and network biology to cancer diagnostics and therapy.
Research projects
Molecular data-driven engineering of immunotherapy
Omics, network and machine learning-based classification of skin and prostate cancer patients
Multi-layered data-based drug repurposing in therapy-resistant cancer patients
Current projects
Deubiquitinase Otud7b in oligodendrocyte differentiation and CNS myelination
Specific regulation of protein degradation by the ubiquitin-proteasome system plays important roles in myelination, remyelination and neurodegenerative diseases. I want to analyse the functions of the deubiquitinase Otud7b in oligodendrocytes in vitro and in vivo in an oligodendrocyte-specific Otud7b knockout mouse model and identify functional targets of Otud7b in oligodendrocytes to deepen the understanding of posttranscriptional regulatory events during OL differentiation and CNS myelination.
An adverse local environment ("niche") impairs the activity of neural stem cells (NSCs) in the adult brain. We investigate the new hypothesis that NSCs play an active role in generating favorable and adverse niche conditions. Specifically, we will investigate how dysfunctional NSCs generate adverse niche conditions focusing i) on the composition and the biomechanical properties of the extracellular matrix and ii) on NSC-derived exosomes and their composition.
CD19-directed chimeric antigen receptor (CAR) T-cells have shown high efficacy in the treatment of B-cell malignancies and are now emerging as a standard approach for patients with relapsed and refractory disease. Despite this progress, a significant portion of patients still experience resistance to treatment. We aim to understand the intrinsic mechanisms controlling persistence and effector functions of CAR T-cells and therefore identify strategies to overcome treatment failure.
Mutations in transcriptional corepressor CtBP1 cause the neurodevelopmental disorder HADDTS. Functional CtBP1 studies in the central nervous system so far focused on neurons. We recently found that CtBP1 is also important in oligodendrocytes. Here we will characterize the oligodendroglial functions of CtBP1 and the underlying cellular and molecular mechanisms in mice and a human ES cell-derived cellular disease model to show that defects in oligodendrogenesis and myelination contribute to HADDTS
Immune-checkpointinhibitors have shown clinical activity in advanced melanoma, withsignificant survival benefit and response rates for anti-CTLA-4(19%), anti-PD-1 (36-44%) and combined therapy (58-61%). Whileresponses can be durable, a significant proportion of patients showautoimmune side effects, including autoimmune colitis, hepatitis andmusculoskeletal side effects. Inabout one third of cases patients exhibit side effects in more thanone organ system. In a fraction of the patients autoimmunity ispresent prior the therapy and may exacerbate. To be able to predictthe risk of appearance of these severe autoimmuneside effectswould enable physicians to personalize the anticancer treatment tothe patient and understanding mechanisms of these autoimmunereactions could improve therapy.
Theaim of the project is to improve our understanding of the molecularand cellular mechanisms underlying the interplay between autoimmunityand cancer, with an interest on the role of predisposing factors inthe appearance or exacerbation of autoimmunity under immunotherapy.The project uses melanoma, inflammatory bowel and rheumatoid diseasesas models. Under the systems medicine paradigm, we will generate invivo/patientdata-based molecular networks and multi-level models accounting forthe mechanisms behind the immune activation involved in theautoimmunity-cancer-immunotherapy axis. Combining data and networkanalysis, computer simulations and model experimentation, we willgenerate molecular and phenotypic signatures accounting for theemergence or enhancement of autoimmunity under checkpointinhibitor therapy, and will correlate these signatures with publishedand denovopatient data. We expect the project to pavethe way towards the translation into clinical practice of systemsmedicine-based methods for monitoring autoimmunity in melanomapatients receiving immunotherapy and establish a basis for rationaletreatment approaches for autoimmunity in cancer patients.
Rivera Monroy, L., Eberhardt, M., Ostalecki, C., Baur, A., Vera, J., & Maier, A. (2022). Melanoma Segmentation and Classification Employing Imaging and Graph Encodings. In Proceedings - 2022 IEEE/ACM International Conference on Connected Health: Applications, Systems and Engineering Technologies, CHASE 2022 (pp. 144-145). Washington, DC, US: Institute of Electrical and Electronics Engineers Inc..
Koch, E., Petzold, A., Wessely, A., Dippel, E., Erdmann, M., Heinzerling, L.,... Heppt, M. (2021). Clinical Prognostic Factors in metastatic Choroidal Melanoma. In JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT (pp. 82-83). HOBOKEN: WILEY.
Jaitly, T., Gupta, S.K., Wolkenhauer, O., Schuler, G., & Vera, J. (2020). Envisioning the application of systems biology in cancer immunology. In Nima Rezaei (Eds.), Cancer Immunology: A Translational Medicine Context. (pp. 599-624). Springer International Publishing.
I am a physicist working in systems and precision medicine applied to cancer and autoimmune diseases. I lead an interdisciplinary team that combines computational modeling, bioinformatics, multi-criteria decision algorithms, and network biology to cancer diagnostics and therapy.
Research projects
Current projects
Deubiquitinase Otud7b in oligodendrocyte differentiation and CNS myelination
(FAU Funds)
How neural stem cells shape their regulatory environment in the adult CNS
(FAU Funds)
Funding source: Mittelgeber / Förderprogramme
An adverse local environment ("niche") impairs the activity of neural stem cells (NSCs) in the adult brain. We investigate the new hypothesis that NSCs play an active role in generating favorable and adverse niche conditions. Specifically, we will investigate how dysfunctional NSCs generate adverse niche conditions focusing i) on the composition and the biomechanical properties of the extracellular matrix and ii) on NSC-derived exosomes and their composition.
Mechanisms controlling functionality and persistence of CD19.CAR T-cells
(FAU Funds)
CtBP1 in oligodendroglial development and myelination
(FAU Funds)
Systems medicine of melanoma and autoimmunity in the context of immunotherapy
(Third Party Funds Single)
Funding source: Bundesministerium für Bildung und Forschung (BMBF)
URL: https://www.melautim.net
Immune-checkpointinhibitors have shown clinical activity in advanced melanoma, withsignificant survival benefit and response rates for anti-CTLA-4(19%), anti-PD-1 (36-44%) and combined therapy (58-61%). Whileresponses can be durable, a significant proportion of patients showautoimmune side effects, including autoimmune colitis, hepatitis andmusculoskeletal side effects. Inabout one third of cases patients exhibit side effects in more thanone organ system. In a fraction of the patients autoimmunity ispresent prior the therapy and may exacerbate. To be able to predictthe risk of appearance of these severe autoimmuneside effectswould enable physicians to personalize the anticancer treatment tothe patient and understanding mechanisms of these autoimmunereactions could improve therapy.
Theaim of the project is to improve our understanding of the molecularand cellular mechanisms underlying the interplay between autoimmunityand cancer, with an interest on the role of predisposing factors inthe appearance or exacerbation of autoimmunity under immunotherapy.The project uses melanoma, inflammatory bowel and rheumatoid diseasesas models. Under the systems medicine paradigm, we will generate invivo/patientdata-based molecular networks and multi-level models accounting forthe mechanisms behind the immune activation involved in theautoimmunity-cancer-immunotherapy axis. Combining data and networkanalysis, computer simulations and model experimentation, we willgenerate molecular and phenotypic signatures accounting for theemergence or enhancement of autoimmunity under checkpointinhibitor therapy, and will correlate these signatures with publishedand denovopatient data. We expect the project to pavethe way towards the translation into clinical practice of systemsmedicine-based methods for monitoring autoimmunity in melanomapatients receiving immunotherapy and establish a basis for rationaletreatment approaches for autoimmunity in cancer patients.
Recent publications
2023
2022
2021
2020
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