Spring Selection 2018

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currently open
closes 7 Jan 2018

Research Groups

Portrait Jared Sterneckert

Jared Sterneckert

iPS Cells and Neurodegenerative Disease

Previous and Current Research

Neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are becoming more and more common, and very little, if anything, can be done to prevent these pathologies from starting or progressing. Therefore, better treatments are urgently needed for these diseases.

Induced pluripotent stem cell (iPSC) technology uniquely enables us to study how ALS and PD occur using patient specific cells. In the past, scientists have had to rely upon animal models or cell lines, which have provided useful insights, but both of these systems can behave differently than patient samples. However, using reprogramming, we can generate iPSC lines using fibroblasts that were donated by a patient with an observable phenotype and known genotype. Through the unique abilities of stem cells, we can theoretically form limitless numbers of specialized cells, including neurons. Using these neurons, we can replay the disease process in a dish and use this as a model to study the molecular mechanisms involved. Excitingly, because stem cells can produce such large numbers of neurons, we can even test for and identify new drug candidates using patient specific neurons.

Recent work from my team provides proof of principle for these concepts. In collaboration with clinicians, we have generated iPSC lines from patients with ALS and PD harboring specific mutations. Using gene correction, we have shown that one of these mutations – LRRK2 G2019S – causes PD through a novel mechanism. In addition, we have developed and patented an innovative differentiation platform technology that enables large-scale application of our disease models, for example for proteomics and drug discovery.

Future Projects and Goals
  • Generation of iPSC-based models of familial and sporadic forms of neurodegenerative disease.
  • Phospho-proteomics of iPSC-based models to identify aberrantly regulated signaling pathways causing neurodegeneration.
  • Phenotypic screening of small molecule libraries using iPSC-based models to identify novel drug candidates and disease mechanisms.
Selected Publications

Distinct Neurodegenerative Changes in an Induced Pluripotent Stem Cell Model of Frontotemporal Dementia Linked to Mutant TAU Protein.
Ehrlich M, Hallmann AL, Reinhardt P, Araúzo-Bravo MJ, Korr S, Röpke A, Psathaki OE, Ehling P, Meuth SG, Oblak AL, Murrell JR, Ghetti B, Zaehres H, Schöler HR, Sterneckert J*, Kuhlmann T*, Hargus G*
Stem Cell Reports. 5(1):83–96 (2015)

Sterneckert JL, Reinhardt P, Schöler HR
Investigating human disease using stem cell models.
Nat Rev Genet. 15(9):625–39 (2014)

Reinhardt P, Glatza M, Hemmer K, Tsytsyura Y, Thiel CS, Höing S, Moritz S, Parga JA, Wagner L, Bruder JM, Wu G, Schmid B, Röpke A, Klinguaf J, Schwamborn JC, Gasser T, Schöler HR**, Sterneckert J**
Derivation and Expansion Using Only Small Molecules of Human Neural Progenitors for Neurodegenerative Disease Modeling.
PLoS ONE. 8(3):e59252 (2013)

Reinhardt P*, Schmid B*, Burbulla LF, Schöndorf DC, Wagner L, Glatza M, Höing S, Hargus G, Heck SA, Dhingra A, Wu G, Müller S, Brockmann K, Kluba T, Maisel M, Krüger R, Berg D, Tsytsyura Y, Thiel CS, Psathaki OE, Klingauf J, Kuhlmann T, Klewin M, Müller H, Gasser T**, Schöler HR**, Sterneckert J.
Genetic Correction of a LRRK2 Mutation in Human iPSCs Links Parkinsonian Neurodegeneration to ERK-Dependent Changes in Gene Expression.
Cell Stem Cell. 12(3):354–67 (2013)

Höing S, Rudhard Y, Reinhardt P, Stehling M, We G, Peiker C, Böcker A, Glatza M, Slack M, Sterneckert J**, Schöler HR**
Discovery of inhibitors of microglial neurotoxicity acting through multiple mechanisms using a stem cell-based phenotypic assay.
Cell Stem Cell. 11(5):620–632 (2012)

(*co-first authors; **co-corresponding authors)

CV

since September 2014
Group Leader, CRTD

2010–2014
Project Group Leader, Max Planck Institute for Molecular Biomedicine (Münster, Germany)

2006–2009
Postdoctoral Research Fellow, Max Planck Institute for Molecular Biomedicine (Hans R. Schöler; Münster, Germany)

1998–2005
Ph.D. Johns Hopkins University (John D. Gearhart; Baltimore, MD, USA)

Contact

Center for Regenerative Therapies Dresden
TU Dresden
Fetscherstraße 105
01307 Dresden

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