Delbrück Fellow

133571

Dr. Alessandro Prigione

31.2: Max-Delbrück Haus (Flachbau)

Raum 1210.2

Tel. 9406-2871

Fax.

Alessandro.Prigione@mdc-berlin.de


Mitochondria and cell fate reprogramming

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.

We are interested in dissecting the contributing role of mitochondria and energy metabolism in enabling cellular conversion. By building a mitochondria-centered model of cell fate reprogramming and differentiation with a targeted neuronal focus, we wish to unveil the relevance of mitochondrial modulation for cell identity, neuronal commitment, reprogramming, and rejuvenation.

Additionally, we seek to apply the iPSC technology for modeling neurological diseases affecting the mitochondria either directly, such as mitochondrial DNA (mtDNA) disorders, or indirectly, like Huntington’s disease (HD). The development of alternative modeling approaches is highly needed for conditions affecting the nervous system, whose understanding has been hindered by the inability to sample live neuronal cells. This is particularly important for mtDNA disorders, which lack viable modeling tools due to the hurdles associated with engineering mtDNA. Reprogramming-derived neurons can be eventually employed as disease-relevant cell type-specific cellular systems for the discovery of novel disease-modifying therapeutic strategies for these untreatable brain disorders.

 

 

Mitochondrial reprogramming

 

System-iPS

 

Team

   

 

 

 

News



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."

 

Press release from the MDC: 

A cellular system makes the battle against a rare disease personal

 

From the Mitochondrial Disease News: 

Cell-reprogramming Method Developed to Test Approved Therapies on Mitochondrial Disease

 

October 2016 Cell Stem Cell Preview published:

"A glycolytic solution for pluripotent stem cells."

 

February 2016 Our Special Issue in Seminars in Cell & Developmental Biology is out!

" Mitochondria and metabolism remodeling in cellular reprogramming and differentiation."

 

 

 

 

Links



 

Twitter account @AlePrigio

https://mitochondrialdiseasenews.com/

http://www.umdf.org

http://www.targeting-mitochondria.com/

http://www.eurostemcell.org/

http://www.gscn.org/

http://www.isscr.org/

Mitochondrial Medicine

Drawing by Helena P.

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

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.