Team
Neuroscience
Studying prenatal human brain development remains a challenge due to limited access to live human brain tissue and ethical constraints on research using human embryos. Recent advances in stem cell biology have revolutionized the field of human developmental biology by allowing us to generate three-dimensional models that recapitulate structural organization of various organs, including the brain.
Our lab focuses on advancing novel stem cell-based technologies to generate three-dimensional models that recapitulate the structural and functional organization of the human brain. We leverage these technologies to push the boundaries for personalized research on human-specific brain disorders and to identify strategies for facilitating brain repair.
Selected Publications:
Schafer, S.T., Paquola, A.C.M., Stern, S., Gosselin, D., Ku, M., Pena, M., Kuret, T.J.M., Liyanage, M., Mansour, A.A., Jaeger, B.N., Marchetto, M.C., Glass, C.K., Mertens, J. & Gage, F.H. (2019) Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons. Nature Neuroscience 22, 243
Herdy, J., Schafer, S.T., Kim, Y., Ansari, Z., Zangwill, D., Ku, M., Paquola, A., Lee, H., Mertens, J. & Gage, F.H. (2019) Chemical modulation of transcriptionally enriched signaling pathways to optimize the conversion of fibroblasts into neurons. eLife 8, e41356
Gonçalves, J.T.*, Schafer, S.T.* & Gage, F.H. (2016) Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. Cell 167, 897–914 [equal contribution]
Han, J., Kim, H.J.*, Schafer, S.T. *, Paquola, A., Clemenson, G.D., Toda, T., Oh, J., Pankonin, A.R., Lee, B.S., Johnston, S.T., Sarkar, A., Denli, A.M. & Gage, F.H. (2016) Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain. Neuron 91, 79–89 [equal contribution]
Schafer, S.T., Han, J., Pena, M., von Bohlen und Halbach, O., Peters, J. & Gage, F. H. (2015) The Wnt Adaptor Protein ATP6AP2 Regulates Multiple Stages of Adult Hippocampal Neurogenesis. J Neurosci 35, 4983–4998
Han, J., Kim, H.J.*, Schafer, S.T. *, Paquola, A., Clemenson, G.D., Toda, T., Oh, J., Pankonin, A.R., Lee, B.S., Johnston, S.T., Sarkar, A., Denli, A.M. & Gage, F.H. (2016) Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain. Neuron 91, 79–89 [equal contribution]
Mertens, J., Wang, Q.W., Kim, Y., Yu, D.X., Pham, S., Yang, B., Zheng, Y., Diffenderfer, K. E., Zhang, J., Soltani, S., Eames, T., Schafer, S.T., Boyer, L., Marchetto, M.C., Nurnberger, J.I., Calabrese, J.R., Oedegaard, K.J., McCarthy, M.J., Zandi, P.P., Alda, M., Nievergelt, C.M., Mi, S., Brennand, K.J., Kelsoe, J.R., Gage, F.H. & Yao, J. (2015) Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 527, 95–99
Contact:
Simon T. Schäfer, PhD
Assistant Professor for Advanced Organoid Technologies for Mental Health Research
Technical University of Munich (TUM)
School of Medicine
Department of Psychiatry and Psychotherapy
TranslaTUM, Center for Organoid Systems
Organoid Hub, Room 22.2.18
Einsteinstr. 25
81675 Munich, Germany
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Imaging
Prof. Schilling conducts research in the field of preclinical molecular imaging. His research focusses on the development of novel methods in the area of magnetic resonance imaging (MRI). Together with his group he characterizes and validates imaging biomarkers. Interdisciplinarity is an essential characteristic of this area of research which combines the development of physical methods, the chemical characterization and synthesis of molecular sensors, as well as the investigation of biological and medical research questions.
Key publications:
Düwel S, Hundshammer C, Gersch M, Feuerecker B, Steiger K, Buck A, Walch A, Haase A, Glaser SJ, Schwaiger M, Schilling F: „Imaging of pH in vivo using hyperpolarized 13C-labeled zymonic acid“. Nature Communications. 2017; 8: 15126.
Schilling F, Ros S, Hu De-En, D’Santos P, McGuire S, Mannion E, Neves AA, Brindle K: „MRI measurements of reporter-mediated increases in transmembrane water exchange enable detection of a gene reporter“. Nature Biotechnology. 2017; 35: 75-80.
Hundshammer C, Düwel S, Köcher S, Gersch M, Feuerecker B, Scheurer C, Haase A, Glaser SJ, Schwaiger M, Schilling F: „Deuteration of hyperpolarized 13C-labelled zymonic acid enables sensitivity-enhanced dynamic MRI of pH“. ChemPhysChem. 2017; 18(18): 2422:2425.
Schilling F, Warner LR, Gershenzon NI, Skinner TE, Sattler M, Glaser SJ: „Next Generation Heteronuclear Decoupling for High Field Biomolecular NMR“. Angewandte Chemie International Edition. 2014; 126(17): 4564-4568.
Schilling F, Düwel S, Köllisch U, Durst M, Schulte RF, Glaser SJ, Haase A, Otto AM, Menzel MI: „Diffusion of hyperpolarized 13C metabolites in tumor cells spheroids using real-time NMR spectroscopy“. NMR in Biomedicine. 2013; 26(5): 557-568.
Oncology
The focus of my Emmy Noether group is to understand and combat cancer cell resistance to CAR-T cell therapy. We aim to improve this innovative therapeutic approach and extend it to a broader patient population in clinical practice.
Selected publications:
Larson, R.C., Kann, M.C., Bailey, S.R., Haradhvala, N.J., Llopis, P.M., Bouffard, A.A., Scarfó, I., Leick, M.B., Grauwet, K., Berger, T.R., Stewart, K., Anekal, P.V., Jan, M., Joung, J., Schmidts, A., Ouspenskaia, T., Law, T., Regev, A., Getz, G., Maus, M.V. (2022). CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours. Nature 604(7906):563-570.
Petri, K.*, Zhang, W.*, Ma, J.*, Schmidts, A.*, Lee, H., Horng, Y.E., Kim, D.Y., Kurt, I.C., Clement, K., Hsu, J.Y., Pinello, L., Maus, M.V., Joung, J.K., Yeh, J.R. (2022). CRISPR prime editing with ribonucleoprotein complexes in zebrafish and primary human cells. Nature Biotechnol. 40(2):189-193. *co-first author
Schmidts, A., Marsh, L.C., Srivastava, A.A., Bouffard, A.A., Boroughs, A.C., Scarfò, I., Larson, R.C., Bedoya, F., Choi, B.D., Frigault, M.J., Bailey, S.R., Leick, M.B., Vatsa, S., Kann, M.C., Prew, M.S., Kleinstiver, B.P., Joung, J.K., Maus, M.V. (2020). Cell-based artificial APC resistant to lentiviral transduction for efficient generation of CAR-T cells from various cell sources. J Immunother Cancer. 8(2):e000990.
Schmidts, A., Wehrli, M., Maus, M.V. (2020). Toward Better Understanding and Management of CAR-T Cell-Associated Toxicity. Annu Rev Med 72:365-382.
Schmidts, A., Ormhoj, M., Choi, B.D., Taylor, A.O., Bouffard, A.A., Scarfo, I., Larson, R.C., Frigault, M.J., Gallagher, K., Castano, A.P., Riley, L.S., Cabral, M.L., Boroughs, A.C., Velasco Cardenas, R.M., Schamel, W., Zhou, J., Mackay, S., Tai, Y.T., Anderson, K.C., Maus, M.V. (2019). Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma. Blood Adv. 3(21):3248-3260.
Choi, B.D., Yu, X., Castano, A.P., Bouffard, A.A., Schmidts, A., Larson, R.C., Bailey, S.R., Boroughs, A.C., Frigault, M.J., Leick, M.B., Scarfò, I., Cetrulo, C.L., Demehri, S., Nahed, B.V., Cahill, D.P., Wakimoto, H., Curry, W.T., Carter, B.S., Maus, M.V. (2019). CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nature Biotechnol. 37(9):1049-1058.
Schmidts, A., Maus, M.V. (2018) Making CAR T Cells a Solid Option for Solid Tumors. Front Immunol. 9:2593.
https://www.translatum.tum.de/translatum/forschungsgruppen-1/andrea-schmidts-car-t-zelltherapien/
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Molecular Medicine
Our research at the Chair of Translational Genomics leverages big data in genetics and genomics for medically important human traits. We aim to translate insights from genomics into mechanisms of disease development and progression, shortening the path to translation and empowering precision medicine. We integrate information gleaned from deep molecular, genomics and epidemiological approaches to address important biomedical research challenges. Our work is underpinned by data generation at scale and by the development of computational genomics toolkits to analyse the wealth of information.
https://www.helmholtz-munich.de/itg/institute/research/index.html