Florian Nigsch, PhD
Chemical Biology & Therapeutics
Our objective is to build and characterize new models for diseases affecting human vision. Many such diseases are due to defects in biogenesis or function of primary cilia, cellular organelles found in sensory organs such as the retina. We want to better understand the pathophysiology of ciliopathies on a molecular level and develop new approaches aimed at finding innovative treatments for this disease group.
Based on recent dramatic advances in induced pluripotent stem cell (iPSC) technology, complex cell-based model systems have become an attractive target for the discovery of new disease-modulating molecular entities. For example, important progress has been made in the generation of human retinal organoids. These so-called optic cups, which resemble the architecture of the human eye including rod and cone photoreceptors, are obtained from iPSCs through self-assembly using appropriate culture conditions. After profiling and molecular characterization of retinal organoids, we want to use current genome editing technologies to build complex cellular models of ocular diseases and conduct pharmacological and genetic screens.
This research project is conducted in close collaboration with Botond Roska at the Friedrich Miescher Institute in Basel, is highly interdisciplinary, and combines current state-of-the-art technologies for producing disease-relevant organotypic systems, methods for single-cell molecular profiling, low-molecular weight and genetic screening, and data analysis methods. Through this comprehensive interrogation of photoreceptor function, we aim to define new starting points for drug discovery.
Causal Network Models for Predicting Compound Targets and Driving Pathways in Cancer
Jaeger S, Min J, Nigsch F, Camargo M, Hutz J, Cornett A, Cleaver S, Buckler A, Jenkins JL.
J Biomol Screen. 2014 Feb 11;19(5):791-802
Rethinking molecular similarity: comparing compounds on the basis of biological activity
Petrone PM, Simms B, Nigsch F, Lounkine E, Kutchukian P, Cornett A, Deng Z, Davies JW, Jenkins JL, Glick M
ACS Chem Biol. 2012 Aug 17;7(8):1399-409
Determination of minimal transcriptional signatures of compounds for target prediction
Nigsch F, Hutz J, Cornett B, Selinger DW, McAllister G, Bandyopadhyay S, Loureiro J, Jenkins JL
EURASIP J Bioinform Syst Biol. 2012 May 10;2012(1):2