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iPS Cells and Neurodegenerative Disease - Jared Sterneckert

Induced pluripotent stem cell (iPSC) technology offers a unique opportunity to study neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Reprogramming enables the generation of iPSC lines directly generated from fibroblasts donated by a patient with an observable phenotype and known genotype. Using iPSCs, theoretically limitless numbers of specialized cells, including neurons, can be generated that carry the same genetic mutations as the donating patient.

Previous and current research

Neurodegenerative diseases such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) cause significant suffering. Aging is one of the biggest risk factors for these diseases, and, as a result, the number of patients having neurodegenerative diseases is rapidly increasing as people live longer - so much so that you likely know someone that is affected. Basic science studies have identified possible drug candidates to prolong neuronal survival in patients. However, these drug candidates have almost universally failed in clinical trials. As a result, physicians can do very little to help patients once diagnosed. more

Future projects and goals

  • Unlike HeLa cells, neurons have axons. Since axons are the first to degenerate in patients, we are generating models of axon degeneration using iPSC-derived neurons. In particular, we are interested in the effects of aging and disease-causing mutations on axons.
  • Together with the Lead Discovery Center GmbH, we are screening small molecules for their ability to protect neurons, including axons, against neurodegeneration.
  • There are two major difficulties in developing new treatments for ALS and PD patients. First, the diseases begin many years before diagnosis, and, second, we often don't know if the drug in question is having the effect on neurons that we want it to have. Biomarkers are critical to addressing both issues. Using iPSCs, and in cooperation with clinical partners, we aim to identify and validate candidate biomarkers to enable earlier diagnosis and facilitate clinical translation of novel therapeutics.

Group leader

Selected publications

Maharana S, Wang J, Papadopoulos DK, Richter D, Pozniakovsky A, Poser I, Bickle M, Rizk S, Guillén-Boixet J, Franzmann T, Jahnel M, Marrone L, Chang YT, Sterneckert J, Tomancak P, Hyman AA, Alberti S. RNA buffers the phase separation behavior of prion-like RNA binding proteins. Science. 2018 Apr 12. pii: eaar7366. doi: 10.1126/science.aar7366.

Marrone L, Bus C, Schöndorf D, Fitzgerald JC, Kübler M, Schmid B, Reinhardt P, Reinhardt L, Deleidi M, Levin T, Meixner A, Klink B, Glatza M, Gloeckner CJ, Gasser T, Sterneckert J. Generation of iPSCs carrying a common LRRK2 risk allele for in vitro modeling of idiopathic Parkinson's disease. PLoS One. 2018 Mar 7;13(3):e0192497.

Marrone L, Poser I, Casci I, Japtok J, Reinhardt P, Janosch A, Andree C, Lee HO, Moebius C, Koerner E, Reinhardt L, Cicardi ME, Hackmann K, Klink B, Poletti A, Alberti S, Bickle M, Hermann A, Pandey UB, Hyman AA, Sterneckert JL. Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule Pathology that Is Rescued by Drugs Inducing Autophagy. Stem Cell Reports. 2018 Feb 13;10(2):375-389.

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)
* indicates co-corresponding authors

Group members

New group members are welcome.
In our lab we are working as a dynamic team to follow our many novel projects. Thus, we are always looking for motivated Master and PhD students or Postdocs to join our endeavor. If you are interested, please send an email to Dr. Jared Sterneckert with a full CV and names of at least two references.

Contact

Group Leader

Jared Sterneckert, PhD
jared.sterneckert[at]crt-dresden.de


Assistant to Group Leader

Daniela Mohrich
daniela.mohrich[at]crt-dresden.de
Phone: +49 (0)351 458 82114