Nicole Meisner-Kober, PhD
Chemical Biology & Therapeutics
While RNA biology is increasingly recognized as an essential layer in the regulation of gene expression, it still remains an underexploited avenue for therapeutic intervention. The Meisner lab is a group of interdisciplinary researchers with the mission to leverage RNA biology as both, target and therapeutics for drug discovery, based on in depth molecular mechanistic understanding. As an example, a recent focus in the lab has been on the identification of rate-limiting steps in the RNAi pathway with the aim to mechanistically improve the efficacy of siRNA therapeutics. In this context we discovered that the rough endoplasmatic reticulum (rER) is the central site of RNA silencing, which will now open up an entirely new path for subcellular targeted siRNA delivery strategies. Further work in this area has focused on resolving the mechanisms in cell uptake and subcellular trafficking of RNA cargo transmitted between cells by exosomes, microvesicles released by virtually all cells. As a second area we have been exploring the drug-ability of posttranscriptional regulation. We have identified the first small molecule inhibitors for the 3’UTR binding protein HuR and were able to reveal an enzymatic activity of this master regulator. A more recent program and current focus in the lab is in the area of RNA toxicity in peripheral nerve diseases such as Amyotrophic Lateral Sclerosis (ALS), where we are aiming to identify rational entry points for therapeutic intervention driven by an in-depth understanding of the underlying RNA pathobiology.
Highly complementary target RNAs promote release of guide RNAs from human Argonaute2.
De N, Young L, Lau PW, Meisner-Kober N, Morrissey D, MacRae I.
Molecular Cell 2013 May 9;50(3):344-55.
The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing.
Stalder L, HeusermannW, Sokol L, Trojer D, Wirz J, Hean J, Fritzsche A, Aeschimann F, Pfanzagl V, Basselet P, Weiler J, Hintersteiner M, Morrissey DV, Meisner-Kober NC.
EMBO Journal 2013 Apr 17;32(8):1115-27.
Identification and mechanistic characterization of low molecular weight inhibitors for HuR.
Meisner NC, Hintersteiner M, Mueller K, Bauer R, Seifert JS, Naegeli HU, Ottl J, Oberer L, Guenat C, Moss S, Harrer N, Woisetschlager M, Buehler C, Uhl V, Auer M.
Nature Chemical Biology 2007 Aug;3(8):508-15.
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