perspective on development
Uncovering the molecular logic of human neuron formation -
from direct reprogramming to cerebral organoids
The vision of the Karow lab is to uncover mechanisms of human neuron formation and to identify new molecular targets not only for enhancing and navigating but also for correcting defective neurogenesis. We are integrating the strength of two complementary approaches to study the formation of human neurons, that is in forced and natural conditions.
Through overexpression of neurogenic transcriptions factors we are forcing neurogenesis in non-neural brain-resident pericytes of the adult human cerebral cortex to obtain lineage conversion into induced neurons (iNs). Our recent work has revealed not only an unprecedented understanding of the intermediate states during the fate change of pericytes into iNs, but also provided new insights into the molecular underpinning of neuron subclass specification. Based on these findings, we now aim at using the iN model system to identify transcriptional programs driving neuronal subtype specification in natural conditions. This will provide not only new cues on the specification of distinct neuron classes, but might also provide new insights in the molecular basis for many neurodevelopmental disorders (including neuropsychiatric disorders) in which this fine-tuned balance of neuron specification is altered.
The tools to investigate this "natural" neurogenesis are centered around cerebral organoids, a model system allowing investigation of early aspects of human neurogenesis. Currently, we are studying the disease etiology of a monogenetic X-linked disorder caused by an intellectual disability-causing mutation.
If you want to know more about our research, please contact us. We are always interested in motivated, curious people with a background in biology, bioinformatics, biomaterials, and medicine.
Marisa Karow, Dr
Elisa Gabassi, MSc
Dandan Han, Dr
Karow M*#, Camp GJ*, Falk S, Gerber T, Pataskar A, Gac-Santel M, Kageyama J, Brazovskaja A, Garding A, Fan Wengiang, Riedemann T, Casamassa A, Schichor C, Götz M, Tiwari VK, Treutlein B#, Berninger B#. Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. 2018. Nature Neuroscience. * co-first authors # co-corresponding authors.
Gascón S, Murenu E, Masserdotti G, Ortega F, Russo GL, Petrik D, Deshpande A, Heinrich C, Karow M, Robertson SP, Schroeder T, Beckers J, Irmler M, Berndt C, Angeli JP, Conrad M, Berninger B, Götz M. Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming. 2016. Cell Stem Cell.
Karow M, Schichor C, Beckervordersandforth R, Berninger B. Lineage-Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neurons. 2014. Journal of Visualized Experiments.
Karow M, Chavez CL, Farruggio AP, Geisinger JM, Keravala A, Jung WE, Lan F, Wu JC, Chen-Tsai Y, Calos MP. Site-specific recombinase strategy to create induced pluripotent stem cells efficiently with plasmid DNA. 2011. Stem Cells.
December 2019 Dandan joins the lab
October 2019 Elisa defended her MSc thesis
September 2019 Marisa is appointed as a professor at the Institute of Biochemistry in the Medical Faculty at the FAU Erlangen
July 2019 DFG project is funded
June 2019 Ben receives Boehringer Ingelheim travel award for the EMBO course on developmental neurobiology
April 2019 Elisa joins the lab with an Erasmus fellowship
February 2019 ForInter project is funded
July 2018 Heiko visited the lab for a very fruitful collaboration
July 2018 Ben is accepted in the IMPRS-TP graduate school
June 2018 Our work is published in Nature Neuroscience. Great collaboration with Gray Camp and Barbara Treutlein