reprogramming-inspired

perspective on development

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Research

Uncovering the molecular logic of human neuron formation -

from direct reprogramming to brain organoids

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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 previous 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 brain 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. 

 
Team

Marisa Karow, Dr

Professor

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Driven by my strong interest in translational aspects of stem cells, I am focusing on the processes induced in somatic cells during forced neurogenesis. My lab then embarked on combining this line of research with studying natural neurogenesis by using the cerebral organoid technology. It is in particular the unprecedented chance to study human neuron formation in a dish that fascinates me. 

In 2019 I joined the Medical faculty of the FAU Erlangen and moved my lab to the Institute of Biochemistry.

Lia Birschmann

Medical Student

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My name is Lia, I am a medicine and translational neuroscience student from Würzburg. The development and regeneration of the nervous system fascinate me particularly. For my medical doctoral thesis, I focus on microtubule alterations causing aberrant neural stem cell decisions. Besides neuroscience I am passionate about arts and rock climbing.

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Sarah Frank, MSc

Graduate Student

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I am Sarah and due to my interest in molecular biology I left my hometown near Hamburg and moved to Freiburg to obtain my bachelor’s degree in Molecular Medicine. In 2019 I moved to Erlangen for my master’s and joined the lab in 2020 for a 3-month internship. In February 2021 I returned to do my master’s thesis here. I am particularly interested in the cerebral organoid technology and how it can provide insights into the pathobiology underlying neurodevelopmental diseases. In my leisure time I enjoy cooking and hiking through the landscape surrounding Erlangen.

Federica Furlanetto, MSc

Graduate Student

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I am Federica, I come from Treviso, a small town near Venice, in Italy. I obtained an MSc degree in Neuroscience from the University of Trieste during which I participated to the Erasmus+ Traineeship Program, that allowed me to do a thesis in neuroncology in Paris at the Sorbonne. I am now a PhD student at FAU, where I use organoids as models to study neurodevelopmental disorders. I am always amazed by the most elegant and complicated organ of our body, the brain. In my spare time I like to listen to all sorts of music and I try to go the sea/ocean as much as I can.

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Filippo Zoppi, MSc

Graduate Student

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I am Filippo and I come from Italy. I graduated from University of Pisa with a thesis on direct astroglia-to-neuron reprogramming. To perform it I spent several months at the Centre of Developmental Biology of King’s College London in the lab of Benedikt Berninger. Since the very first moment of my career I have been interest into the molecular aspects of cell fate specification in the human brain development. During my PhD I will use direct pericyte-to-neuron reprogramming as a tool to identify novel key-players of human neurogenesis. In my free time I do love hiking and watching auteur movies. I am deeply passionate about contemporary history.

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Linda Petrucci, MSc

Graduate Student

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I graduated with a MSc degree in neurobiology. Since the beginning of my studies neurodevelopment has always fascinated me particularly, with a special interest 3D cell-based approaches and translational applications of stem cells research. During my PhD I will focus on common molecular mechanisms between pericytes-to-neurons reprogramming and human neurogenesis. I love photography, the sun and the sea, and in my free time I like to visit new places and to spend time in the nature.

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shared project with

Negar Nayebzadeh, MSc

Graduate Student

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I am Negar, and I am from Iran. I have studied biochemistry at the BSc level and human genetics at the Masters.
I am passionate about programming and neuroscience, especially neural reprogramming. In Ph. D. I am going to work on pericyte cell reprogramming and their heterogeneity among different donors.In terms of hobbies, I am a fan of bullet-journaling and DIY handicrafts.

Benjamin Lohrer, MSc

Graduate Student

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I graduated with a M.Sc. in Molecular Biology / Neuroscience from Heidelberg University and I am really fascinated by the idea of generating new neurons in adult human brains. In my PhD project, I therefore investigate the intermediate 'switch' state during direct pericyte-to-neuron reprograming. The same qualities I use for cell & organoid culture and scRNA-seq experiments in the lab, I apply as a passionate balcony gardener and cook at home.

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Doris Jaegers

Lab Technician

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I am the Lab-Dinosaur. I´ve been working at the Institute of Biochemistry since 1993. Now I´m looking forward to join and support Marisas team and to work on exciting research projects.

In my spare time I love to dance and travel a lot.

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Alumni
 
Selected publications
  • Herrero-Navarro A, Buche-Aroca L, Moreno-Juan V, Sempere-Ferrandez A, Espinosa A, Susan R, Torres-Masjoan L, Leyva-Diaz E, Karow M, Figueres-Onate M, Lopez-Mascaraque L, Lopez-Atalaya JP, Berninger B, Lopez-Bendito G. Astrocytes and neurons share region-specific transcriptional signatures that confer regional identity to neuronal reprogramming. 2021. Sci Adv. 

    Pubmed

  • Falk S*, Han D, Karow M*. Cellular identity through the lens of direct lineage reprogramming. 2021. Curr Opin Genet Dev. * co-corresponding authors

      Pubmed

  • 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.

       Pubmed     Nature Neuroscience          PMC          GEO          ENA         Altmetric

  • 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.

       Pubmed           Cell Stem Cell          Preview         PlumX

  • 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.

       Pubmed           JOVE          PMC        

  • Karow M, Sánchez R, Schichor C, Masserdotti G, Ortega F, Heinrich C, Gascón S, Khan M, Lie DC, Dellavalle A, Cossu G, Goldbrunner R, Götz M, Berninger B.Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. 2012. Cell Stem Cell.

       Pubmed           Cell Stem Cell          PlumX

  • Lan F, Liu J, Narsinh KH, Hu S, Han L, Lee AS, Karow M, Nguyen KH, Nag D, Calos MP, Robbins RC, Wu, JC. Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Technique. 2012. Circulation.

       Pubmed           Circulation          PMC

       Pubmed           Stem Cells          PMC

News
 
  • We welcome Linda and Negar as new PhD students in the lab!

  • Our first 2 medical students join the lab. A warm welcome to Hanna and Lia!

  • Marisa is Co-Editor of the Frontiers Research Topic Neuronal Identity from Fate Specification to Function See more at: https://www.frontiersin.org/research-topics/15075/neuronal-identity-from-fate-specification-to-function 

  • We all welcome Janine as a new PhD student in the lab

  • Our new lab logo is here! Credits to our friend Dr. Heiko Brennenstuhl

  • 2021 Federica and Filippo start her PhD journey in the lab

  • February 2021 Sarah embarks on her master thesis

  • December 2020 we receive funding from the Jochen-Kalden-Funding-Programme of the IZKF Medical Faculty FAU) N7 Forging neural cell identity 

  • October 2020-December 2020 Bastian Meth performs his Bachelor thesis on the role of mechanical forces on neural stem cells (great collaboration with Sven Falk´s and Silvia Budday´s lab) 

  • June-December 2020 research visit of Florencia Vega Benedetti, PhD 

  • 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

  • June 2018 Our work is published in Nature Neuroscience. Great collaboration with Gray Camp and Barbara Treutlein

 
Lab life
Ben handing in his thesis. YAY!
Ben handing in his thesis. YAY!

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First BBQ of the summer 22
First BBQ of the summer 22

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Outdoor lab meeting
Outdoor lab meeting

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Ben handing in his thesis. YAY!
Ben handing in his thesis. YAY!

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1/17
 
 
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