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

Mitochondria and cell fate reprogramming

Research

Mitochondria and energy metabolism in cell fate conversion and neural commitment

Team

Mitochondria and cell fate reprogramming

Publications

AG Prigione

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.

Announcement:

June 29, 2018 at 12 p.m. : Live Streaming Webinar on Stem Cell Metabolism w/ Alessandro Prigione, Heather Christofk & Michael Teitell

June 2018

The new reviews from our lab:

Mitochondria and the dynamic control of stem cell homeostasis. @ EMBO reports

Pluripotent Stem Cells for Uncovering the Role of Mitochondria in Human Brain Function and Dysfunction. @ J Mol Biol.

Mitochondrial metabolism in early neural fate and its relevance for neuronal disease modeling. @ Curr Opin Cell Biol.

February 2018

JMB Career Advancement Initiative: Spotlight on Early Career Researchers: Alessandro Prigione

BMBF newsletter on Rare Disease Day (Feb. 28, 2018) features our work: Neue Wirkstoffe gegen seltene Erbkrankheiten

November 2017

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

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.

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.