Neonatology and Pediatric Cardiology
University Children’s Hospital
The group of Alessandro Prigione bridges two different research areas: i) human induced pluripotent stem cells (iPSCs)-based neuronal disease modeling, and ii) mitochondrial metabolism. The focus is to dissect the mechanisms underlying the neuronal pathology caused by mitochondrial disorders and to investigate the importance of mitochondrial impairment in early-onset neurodegeneration.
In our lab, we use patient-derived iPSCs to generate neuronal/glial cells and cerebral organoids carrying patient-specific mutations within nuclear DNA or mitochondrial DNA. With these model systems, we can begin to dissect how mutations affecting mitochondrial function can trigger neuronal pathology. In particular, we have a primary focus on Leigh syndrome, which is the most severe form of mitochondrial disease in children.
Our goal is not only to advance the mechanistic understanding of diseases, but also to discover potential treatments. After having identified mutation-specific cellular phenotypes in our iPSC-derived neuronal models, we carry out high-throughput screenings to possibly identify therapeutic compounds.
We integrate stem cell technology, neuronal and glial differentiation in 2D and 3D (cerebral organoids), CRISPR/Cas9-based genome engineering, and mitochondrial-specific assays with high-content analysis (HCA) and compound screenings centered on mitochondrial and neuronal function.
- iPSC-based modeling of Leigh syndrome (BMBF eBio project)
- Mechanistic dissection of the mitochondrial impairment occurring in early-onset Huntington’s disease (DFG project)
- Mitochondrial and metabolic coupling in human neurons and astrocytes
- High-content analysis (HCA) and compound screenings for mitochondrial neuronal toxicity
- Scior A, Arnsburg K, Iburg M, Juenemann K, Pigazzini ML, Mlody B, Puchkov D, Ast A, Buntru A, Priller J, Wanker EE, Prigione A, Kirstein J. Complete suppression of Htt fibrilization and disaggregation of Htt fibrils by a trimeric chaperone complex. EMBO J. 2018 Jan 17;37(2):282-299. PubMed
- Lorenz C, Prigione A. Mitochondrial metabolism in early neural fate and its relevance in neuronal disease modeling. Curr Opin Cell Biol. 2017 Dec;49:71-76. PubMed
- Inak G, Lorenz C, Lisowski P, Zink A, Mlody B, Prigione A. Concise Review: Induced Pluripotent Stem Cell-Based Drug Discovery for Mitochondrial Disease. Stem Cells. 2017 Jul;35(7):1655-1662. PubMed
- Lorenz C, Lesimple P, Bukowiecki R, Zink A, Inak G, Mlody B, Singh M, Semtner M, Mah N, Leong M, Auré K, Pfiffer V, Fauler B, Eichhorst J, Lyras EM, Wiesner B, Priller J, Huebner N, Mielke T, Meierhofer D, Izsvák Z, Meier JC, Bouillaud F, Adjaye J, Wanker E, Schuelke M, Lombès A, Prigione A. Human iPSC-derived neural progenitors are an effective drug discovery model for neurological mtDNA disorders. Cell Stem Cell. 2017, May 4;20(5):659-674. PubMed
- Mlody B, Prigione A. A Glycolytic Solution for Pluripotent Stem Cells. Cell Stem Cell. 2016, Oct 6;19(4):419-420. PubMed
- Wang J, Xie G, Singh M, Ghanbarian AT, Raskó T, Szvetnik A, Cai H, Besser D, Prigione A, Fuchs N, Schumann G, Chen W, Lorincz MC, Ivics Z, Hurst LD, Izsvák Z. Primate-specific endogenous retrovirus driven transcription defines naïve-like stem cells. Nature. 2014, Dec 18;516(7531):405-9. [IF: 42.3] PubMed
- Prigione A, Rohwer N, Hoffmann S, Mlody B, Drews K, Bukowiecki R, Bluemlein K, Wanker EE, Ralser M, Cramer T, Adjaye J. HIF1α modulates cell fate reprogramming through early glycolytic shift and up-regulation of PDK1-3 and PKM2. Stem Cells. 2014 Feb;32(2):364-76. PubMed
- Prigione A, Lichtner B, Kuhl H, Struys EA, Wamelink M, Lehrach H, Ralser M, Timmermann B, Adjaye J. Human iPSCs Harbor Homoplasmic and Heteroplasmic Mitochondrial DNA Mutations While Maintaining hESC-Like Metabolic Reprogramming. Stem Cells. 2011 Sep;29(9):1338-48. PubMed
- Prigione A, Fauler B, Lurz R, Lehrach H, Adjaye J. The Senescence-Related Mitochondrial /Oxidative Stress Pathway is Repressed in Human Induced Pluripotent Stem Cells. Stem Cells. 2010 Apr;28(4):721-33. PubMed
- Prigione A, Cortopassi G. Mitochondrial DNA deletions induce the adenosine monophosphate-activated protein kinase energy stress pathway and result in decreased secretion of some proteins. Aging Cell. 2007 Oct;6(5):619-30. PubMed