Shoichet Lab

Translational Genomics - Molecular and Cellular Neurobiology

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Research

The field of human genetics has changed dramatically over the last two decades. After years of collaborative work, the human genome sequence was first published in 2001; now, with modern technologies, complete individual genomes can be sequenced for relatively small fees within a matter of days, and we have entered a new era of research on the genetic basis of human variation and disease. The array of accessible sequence data provides us with a vast amount of information on molecular alterations underlying neuropsychiatric disorders, but this step reflects only the first hurdle in the process of developing treatment strategies that benefit patients. The next critical step – understanding disease mechanism – is the bottleneck in the translational process. This area is the focus of our work. Genetic studies have highlighted that numerous transmembrane receptors, cell adhesion molecules, and multiple scaffolding proteins at the postsynaptic density (PSD) have been implicated in autism and related developmental disorders, highlighting this structure as an obvious target for detailed study. In my lab, we combine genetic and pharmacological approaches with advanced image analysis techniques to explore molecular events that potentially influence the formation and function of synapses and the generation of functional neuronal networks.

Selected Publications

Rademacher N, Kuropka B, Kunde SA, Wahl MC, Freund C, Shoichet SA. Intramolecular domain dynamics regulate synaptic MAGUK protein interactions. Elife. 2019;8. 

Zieger H, Kunde S-A, Rademacher N, Schmerl B, Shoichet S. Disease-associated scaffold protein CNK2 modulates PSD size and influences trafficking of new synaptic binding partner TNIK. bioRxiv. 2019:532374.

Wegener S, Buschler A, Stempel AV, Kang SJ, Lim CS, Kaang BK, Shoichet SA, Manahan-Vaughan D, Schmitz D. Defective Synapse Maturation and Enhanced Synaptic Plasticity in Shank2 Deltaex7(-/-) Mice. eNeuro. 2018;5(3).

Kunde SA, Rademacher N, Zieger H, Shoichet SA. Protein kinase C regulates AMPA receptor auxiliary protein Shisa9/CKAMP44 through interactions with neuronal scaffold PICK1. FEBS Open Bio. 2017;7(9):1234-45.

Rademacher N*, Schmerl B*, Lardong JA, Wahl MC, Shoichet SA. MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density. Sci Rep. 2016;6:35283.

Schuster S, Rivalan M, Strauss U, Stoenica L, Trimbuch T, Rademacher N, Parthasarathy S, Lajko D, Rosenmund C, Shoichet SA, Winter Y, Tarabykin V, Rosario M. NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse. Mol Psychiatry. 2015;20(9):1120-31.

Rademacher N, Kunde SA, Kalscheuer VM, Shoichet SA. Synaptic MAGUK multimer formation is mediated by PDZ domains and promoted by ligand binding. Chem Biol. 2013;20(8):1044-54.

Kunde SA, Rademacher N, Tzschach A, Wiedersberg E, Ullmann R, Kalscheuer VM, Shoichet SA. Characterisation of de novo MAPK10/JNK3 truncation mutations associated with cognitive disorders in two unrelated patients. Hum Genet. 2013;132(4):461-71.

Schmeisser MJ*, Ey E*, Wegener S*, Bockmann J, Stempel AV, Kuebler A, Janssen AL, Udvardi PT, Shiban E, Spilker C, Balschun D, Skryabin BV, Dieck S, Smalla KH, Montag D, Leblond CS, Faure P, Torquet N, Le Sourd AM, Toro R, Grabrucker AM, Shoichet SA, Schmitz D, Kreutz MR, Bourgeron T, Gundelfinger ED, Boeckers TM. Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2. Nature. 2012;486(7402):256-60.

Shoichet SA, Duprez L, Hagens O, Waetzig V, Menzel C, Herdegen T, Schweiger S, Dan B, Vamos E, Ropers HH, Kalscheuer VM. Truncation of the CNS-expressed JNK3 in a patient with a severe developmental epileptic encephalopathy. Hum Genet. 2006;118(5):559-67.

Shoichet SA, Malik TH, Rothman JH, Shivdasani RA. Action of the Caenorhabditis elegans GATA factor END-1 in Xenopus suggests that similar mechanisms initiate endoderm development in ecdysozoa and vertebrates. Proc Natl Acad Sci U S A. 2000;97(8):4076-81

Team

Sarah A. Shoichet | group leader | sarah.shoichet(at)charite.de
Stella-Amrei Kunde | postdoc | stella-amrei.kunde(at)charite.de
Nils Rademacher | postdoc | nils.rademacher(at)charite.de
Bettina Schmerl | PhD student | bettina.schmerl(at)charite.de
Hanna Zieger | PhD student |
Katie Cuthill | MSc student |

 

Contact

Sarah A. Shoichet
Charité-Universitätsmedizin Berlin
Neuroscience Research Center / Charité CrossOver
Tel: +49 30 450 539 099
Email: sarah.shoichet(at)charite.de