Neurons differentiating from colonies of neural progenitors

Delbrück Fellow: Alessandro Prigione

Mitochondria and cell fate reprogramming

Our overall research interest is to dissect the contributing role of mitochondria and energy metabolism in cell fate conversion and neural commitment and to use this knowledge for the development of stem cell-based therapeutic screenings for incurable neurological mitochondrial disorders.

Mitochondrial Medicine BMBF e:BIO Junior Research Group

Induced pluripotent stem cells (iPSCs), generated through reprogramming of somatic cells back into an embryonic-like pluripotent state, hold great promises for biomedical research. The fundamental discovery that the cellular identity is plastic and amenable to be directed into different epigenetic states highlights the importance of cellular adaptations to novel environments and functional tasks. However, the nuclear-centric view of cell fate is no longer sufficient to fully describe these rapid and dramatic restructurings.

Our work focuses on the contributing role of mitochondria and energy metabolism in cellular plasticity and neural fate induction. We wish to build an iPSC-based approach for advancing the understanding and treatment of debilitating genetic brain disorders due to mitochondrial impairment.

The iPSC technology might lead to a novel paradigm in brain drug development of mitochondrial disorders, allowing the generation of live neural cells capable of recapitulating the genotype/metabotype of the affected tissues within the patients. Phenotypic preclinical compound screenings conducted on such patient-specific material may enable the identification of disease-modifying treatment strategies.

News

News from our Lab

November 2017

Best Scientific Images Contest: 2nd place for Gizem Inak

Best Scientific Images Contest: 2nd place for Gizem Inak

Phd Publication Price: 2nd place for Carmen Lorenz
(Lorenz et al. 2017)

Agilent Seahorse, webinar
http://www.agilent.com/en-us/training-events/eseminars/advancebio-eseminar-series

Thermo Fisher Scientific, 24 Hours of Stem Cells, webinar
https://www.thermofisher.com/de/de/home/about-us/events/life-science/24-hours-stem-cells.html

May 2017

Stem Cells concise review published: 
"Induced Pluripotent Stem Cell-Based Drug Discovery for Mitochondrial Disease"

February 2017

MDC INSIGHTS featuring our research: 
"Alessandro Prigione: Modelling mitochondrial disease"

January 2017

Our manuscript on mitochondrial disease drug discovery is out in Cell Stem Cell:
"Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders." 
Free access to the article until June 23, 2017

October 2016

Cell Stem Cell Preview published: 
"A glycolytic solution for pluripotent stem cells."

February 2016

Our Special Issue in Seminars in Cell & Developmental Biologyis out! 
" Mitochondria and metabolism remodeling in cellular reprogramming and differentiation."

Mitochondrial Medicine

 

Mitochondria are membrane-bound organelles acting as the power plants of the cell, because they generate most of the cell's supply of adenosine triphosphate (ATP). They have their own genome and also divide independently of the cell in which they reside. In addition to their bioenergetic role, mitochondria are involved in a number of cellular functions, including calcium and redox homeostasis signaling, cellular differentiation, apoptosis, as well as in the maintenance of cell cycle and growth.

Mitochondrial impairment has been implicated in several human diseases, such as Leigh syndrome, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, and Autism. Mitochondrial disorders due to mutations in the mitochondrial DNA affect 1/5000 newborns. The nervous system is usually most affected, highlighting the dependence of neurons on mitochondrial functionality. No therapy or treatments currently exist, making mitochondrial diseases a significant burden for society.

iPSCs

induced pluripotent stem cells

iPSC-colony (red: NANOG)

Induced pluripotent stem cells (iPSCs) are generated by reprogramming adult somatic cells through forced expression of stem cell-specific transcription factors or related small molecules. iPSCs hold great promises in biomedical applications. Because they can propagate indefinitely, as well as give rise to every other cell type in the body, they may be employed for replacing defined tissues lost to damage or disease. Moreover, they can be used for model complex human disorders “in a dish”. Finally, iPSC derivatives may represent innovative cellular systems for the development of phenotype-driven drug discovery.