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Cell fate programming and reprogramming; generation of functional neurons in a dish.

Principal investigator; Parmar, Malin, , PhD

Clinical speciality:

Phone: ++46462220620

Co-workers: Anders Björklund, Audrey Dufour, Lachlan Thompson

International networks: NeuroStemcell
TransEuro

Research area/areas: Cell and Molecular Biology, Medical Biotechnology (focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Neurosciences

The main goal in our laboratory is to understand genes and mechanisms controlling specification of human neural cells, and to use this knowledge to generate authentic and subtype-specific functional neurons from human stem cells or other sources. The long-term goal is to develop cells for use in cell replacement therapies for brain repair.

My group studies the molecular specification of human neurons, By gaining a better understanding of how specific types of neurons are formed during normal development in vivo as well as in cell culture, we hope to be able to manipulate cultured neural progenitor cells into making a clinically relevant cell type, such as a mesencephalic dopaminergic (mesDA) neuron or a striatal projection neuron. For thus work, we use two primary sources: human embryonic stem cells (hESCs) cells and human fibroblasts that we subsequently reprogram into neurons.
In our hESC studies we utilize developmental cues to obtain regionalization and subtype specification. In our re-programming studies we use genes and microRNAs expressed by specific populations of cells to create neurons from fibroblasts. In both cases, we test the phenotype and functionality of cells in vitro using gene and microRNA profiling, protein expression analysis, electrophysiology and amperometry. We also analyze the cells after transplantation into rodent brain using histology and amperometry. Additionally, we assays for behavioural recovery in animal models of neurodegenerative disease.

These studies will further our understanding of how neural progenitor cells are specified into a specific type of neuron. We will also gain more knowledge about the plasticity of these cells, and try to identify both cell-specific and environmental factors capable of re-specifying and reprogramming neural cells so that they produce authentic and functional subtype specific neurons.

Link to project homepage: http://www.med.lu.se/expmed/developmental_neurobiology

5 recent original publications

Pfisterer Ulrich, Wood James, Nihlberg Kristian, Hallgren Oskar, Bjermer Leif, Westergren-Thorsson Gunilla, Lindvall Olle, Parmar Malin
Efficient induction of functional neurons from adult human fibroblasts.
Cell cycle (Georgetown, Tex.). 2011; 10: -

Pfisterer Ulrich, Kirkeby Agnete, Torper Olof, Wood James, Nelander Jenny, Dufour Audrey, Björklund Anders, Lindvall Olle, Jakobsson Johan, Parmar Malin
Direct conversion of human fibroblasts to dopaminergic neurons.
Proceedings of the National Academy of Sciences of the United States of America. 2011; 108: 10343 - 10348

Sachdeva Rohit, Jönsson Marie, Nelander Jenny, Kirkeby Agnete, Guibentif Carolina, Gentner Bernhard, Naldini Luigi, Björklund Anders, Parmar Malin, Jakobsson Johan
Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors.
Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 11602 - 11607

Pfisterer Ulrich, Kirkeby Agnete, Torper Olof, Wood James, Nelander Jenny, Dufour Audrey, Björklund Anders, Lindvall Olle, Jakobsson Johan, Parmar Malin
Direct conversion of human fibroblasts to dopaminergic neurons.
Proceedings of the National Academy of Sciences of the United States of America. 2011; 108: 10343 - 10348

Sachdeva Rohit, Jönsson Marie, Nelander Jenny, Kirkeby Agnete, Guibentif Carolina, Gentner Bernhard, Naldini Luigi, Björklund Anders, Parmar Malin, Jakobsson Johan
Tracking differentiating neural progenitors in pluripotent cultures using microRNA-regulated lentiviral vectors.
Proceedings of the National Academy of Sciences of the United States of America. 2010; 107: 11602 - 11607

Further publications here (new window)

Financing/year