Neuroscience

Schäfer, Simon Thomas

Engineering advanced Organoid Systems to Study Human Brain Development, Disease and Repair

The Schäfer Lab focuses on advancing novel stem cell-based technologies to push the boundaries for personalized research on human-specific brain disorders and to identify strategies for facilitating brain repair.

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.

Personalized Human Disease Models to Study Brain Disorders. While specific phenotypes thought to be associated with neuropsychiatric disorders are currently the subject of active research, the question of whether such disease-associated changes represent the consequences of an ongoing and dynamically aberrant developmental process has received less attention. Our lab focuses on dissecting the cellular and developmental origin of mental disorders by using novel approaches that combine comprehensive clinical assessments with patient-specific biological phenotyping. We are particularly interested to dissect cell type-specific principles that govern the dynamic control of human brain development and at the same time introduce a selective vulnerability for human-specific disorders. Identifying “when” and “where” during development a disease signature first emerges has the potential to facilitate pre-symptomatic or, potentially prenatal, diagnosis and risk assessment. We envision that the novel strategies developed here will lead to advances i         n mechanism discovery and diagnosis of mental disorders to ensure an early initiation of personalized treatment programs.

Advanced Neuro-Immune Models for Developing Therapies and Guiding Brain Repair. A specialized population of tissue-resident immune cells known as microglia are thought to play a central role in brain development, homeostasis and tissue repair. Our lab is particularly interested to develop technologies that allow us to study how these tissue-resident immune cells communicate with the human brain. We want to understand the cellular and molecular mechanisms by which microglia orchestrate developmental processes in order to devise targeted strategies for facilitating brain repair.

 

Selected Publications:

S.T. Schafer, A.C.M. Paquola, S. Stern, D. Gosselin, M. Ku, M. Pena, T.J.M. Kuret, M. Liyanage, A.A. Mansour, B.N. Jaeger, M.C. Marchetto, C.K. Glass, J. Mertens, F.H. Gage

Pathological priming causes developmental gene network heterochronicity in autistic subject-derived neurons

Nature Neuroscience 22(2), 243–255 https://10.1038/s41593-018-0295-x

[featured as Editor’s Choice in Science Translational Medicine, recommended by F1000Prime]

A.A. Mansour*., S.T. Schafer* & F.H. Gage

Cellular complexity in brain organoids: Current progress and unsolved issues.

Semin. Cell Dev. Biol. [*equal contribution] https://10.1016/j.semcdb.2020.05.013

 

A. Nott, I.R. Holtman, N.G. Coufal, J.C.M. Schlachetzki, M. Yu, R. Hu, C.Z. Han, M. Pena, J. Xiao, Y. Wu, Z. Keulen, M.P. Pasillas, C. O’Connor, C.K. Nickl, S.T. Schafer, Z. Shen, R.A. Rissman, J.B. Brewer, D. Gosselin, D.D. Gonda, M.L. Levy, M.G. Rosenfeld, G. McVicker, F.H. Gage, B. Ren, C.K. Glass

Brain cell type–specific enhancer-promoter interactome maps and disease risk association

Science 366, 1134–1139. https://10.1126/science.aay0793

J. Mertens, J.R. Herdy, L. Traxler, S.T. Schafer, J.C.M. Schlachetzki, L. Böhnke, D.A. Reid, H. Lee, D. Zangwill, D.P. Fernandes, R.K. Agarwal, R. Lucciola, L. Zhou-Yang, L. Karbacher, F. Edenhofer, S. Stern, S. Horvath, A.C.M. Paquola, C.K. Glass, S.H. Yuan, M. Ku, A. Szücs, L.S.B. Goldstein, D. Galasko, F.H. Gage

Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients

Cell Stem Cell. 28(9), 1533-1548 https://doi.org/10.1016/j.stem.2021.04.004.

S.T. Schafer & F.H. Gage

The When and Where: Molecular and Cellular Convergence in Autism.

Biological Psychiatry 89 (5), 419-420; https://10.1016/j.biopsych.2020.12.016

J.R. Herdy, S.T. Schafer, Y. Kim, Z Ansari, D. Zangwill, M. Ku, A.C.M. Paquola, H. Lee, J. Mertens, F.H. Gage

Chemical modulation of transcriptionally enriched signaling pathways to optimize conversion of fibroblasts into neurons

eLife 8, e41356; https://10.7554/eLife.41356

J.T. Gonçalves*, S.T. Schafer*, F.H. Gage

Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior

Cell 167, 897-914. [*Co-first authors]; https://10.1016/j.cell.2016.10.021

J. Han, H.J. Kim*, S.T. Schafer*, A. Paquola, G.D. Clemenson, A.R. Pankonin, A.M. Denli,

and F.H. Gage

Functional Implications of miR-19 in the Migration of Newborn Neurons in the Adult Brain

Neuron 91(1):79-89 [*Co-second authors]; https://10.1016/j.neuron.2016.05.034

S.T. Schafer*, J. Han, M. Pena, O. von Bohlen und Halbach, J. Peters & F.H. Gage

The Wnt adaptor protein ATP6AP2 regulates multiple stages of adult hippocampal  neurogenesis

J Neuroscience 35(12): 4983-4998 [featured article, *corresponding Author]

https://10.1523/JNEUROSCI.4130-14.2015

J. Mertens, Q. Wang, Y. Kim, D.X. Yu, S. Pham, B. Yang, Q. Wang, Y. Zheng, K.E. Diffenderfer, J. Zhang, S. Soltani, T.J. Eames, S.T. Schafer, L. Boyer, M.C. Marchetto, J.I. Nurnberger, J.R. Calabrese, K.J. Ødegaard, M.J. McCarthy, P.P. Zandi, M. Alba, C.M. Nievergelt, The Pharmacogenomics of Bipolar Disorder Study, S. Mi, K.J. Brennand, J.R. Kelsoe†, F.H. Gage† and J. Yao†

Differential Responses to Lithium in Hyperexcitable Neurons from Bipolar Patients

Nature 527(7576):95-9; https://10.1038/nature15526

URL to my full list of published work: https://www.ncbi.nlm.nih.gov/myncbi/1P_N5wwQ050kI/bibliography/public/

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