Jared Sterneckert – iPS Cells and Neurodegenerative Disease


Jared Sterneckert

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

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

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

from September 2014 Group Leader, CRTD

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 prospects and goals

  • Generation of iPSC-based models of genetic 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.

 

Group Members

List of group members

 

Selected Publications

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


Lojewski X, Staropoli JF, Biswas-Legrand S, Simas AM, Haliw L, Selig MK, Coppel SH, Goss KA, Petcherski A, Chandrachud U, Sheridan SD, Lucente D, Sims KB, Gusella JF, Sondhi D, Crystal RG, Reinhardt P, Sterneckert J, Schöler H, Haggarty SJ, Storch A, Hermann A, Cotman SL. Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway. Hum Mol Genet. 2013; 23(8):2005-22.


Dakas PY, Parga JA, Höing S, Schöler HR, Sterneckert J, Kumar K, Waldmann H. Discovery of neuritogenic compound classes inspired by natural products. Angew Chem Int Ed Engl 2013; 52(36): 9576-81.


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 2013; 8(3): e59252.


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 2013; 12(3): 354-67.

 

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 2012; 11(5): 620-632.


Fischedick G*, Klein DC*, Wu G, Esch D, Höing S, Han DW, Reinhardt P, Hergarten K, Tapia N, Schöler HR, Sterneckert JL. Zfp296 is a novel, pluripotent specific reprogramming factor. PLoS ONE 2012; 7(4): e34645.


Sternckert J, Höing S, Schöler HR. Oct4 and More: The Reprogramming Expressway. Stem Cells 2012; 30(1): 15-21.


Sterneckert J, Stehling M, Bernemann C, Araúzo-Bravo MJ, Greber B, Gentile L, Ortmeier C, Sinn M, Wu G, Ruau D, Zenke M, Brintrup R, Klein DC, Ko K, Schöler HR. Neural induction intermediates exhibit distinct roles of Fgf signaling. Stem Cells 2010; 28(10): 1772-81.


Kerr CL, Letzen B, Hill CM, Agrawal G, Thakor NV, Sterneckert J, Gearhart JD, All A. Efficient differentiation of human embryonic stem cells into oligodendrocyte progenitors for application in a rat contusion model of spinal cord injury. Int J Neurosc 2010; 120(4):305-13.


Greber B, Wu G, Bernemann C, Joo JY, Han DW, Ko K, Tapia N, Sabour D, Sterneckert J, Tesar P, Schöler HR. Conserved and divergent roles of FGF signaling in mouse epiblast stem cells and human embryonic stem cells. Cell Stem Cell 2010; 6(3):215-226.

Last Modified: 30/05/2016