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Transcriptomics in delineation of complex diseases as well as drug repurposing

CRTD Seminar

Date:17.12.2019, 11:00 - 12:00
Speaker: Prof. Dr. Stefan Jovinge, Fredrik Meijer Heart and Vascular Institute, Spectrum Health
Location: CRTD, ground floor, auditorium left
Host: Dr. Olaf Bergmann

"Patients with rare diseases such as monogenetic cardiomyopathies are in desperate need for drugs targeting their disease. The cost of drug development from initial concept to FDA approval has been estimated to be about 2.6 billion USD.  With high throughput transcriptomics the Library of Integrated Network-based Cellular Signatures (LINCS) has publicly released transcriptional profiles quantifying the effects of more than 25,000 perturbagens on the expression of 978 genes in up to 77 cell lines. We have cross-referenced drugs across the whole database ending up with 1.3 billion data points. With this strategy we identified drugs to target the consequences of Lamin A/C haploinsufficiency causing dilated cardiomyopathy with severe arrhythmogenicity. These drugs which have already been approved for the use in humans and can be repurposed. This approach comes at a fraction of the cost of traditional drug development through transcriptional matching the disease to the drugs in the database and sequential testing of the candidate drugs against iPSC derived cardiomyocytes from healthy and diseased humans."  

1: Milliron HY, Weiland MJ, Kort EJ, Jovinge S. Isolation of Cardiomyocytes
Undergoing Mitosis with Complete Cytokinesis. Circ Res. 2019 Oct 25.
2: Li G, Tian L, Goodyer W, Kort EJ, Buikema JW, Xu A, Wu JC, Jovinge S, Wu SM.
Single cell expression analysis reveals anatomical and cell cycle-dependent
transcriptional shifts during heart development. Development. 2019 Jun
3: Kort EJ, Jovinge S. Streamlined analysis of LINCS L1000 data with the slinky
package for R. Bioinformatics. 2019 Sep 1;35(17):3176-3177.
4: Marinković G, Grauen Larsen H, Yndigegn T, Szabo IA, Mares RG, de Camp L,
Weiland M, Tomas L, Goncalves I, Nilsson J, Jovinge S, Schiopu A. Inhibition of
pro-inflammatory myeloid cell responses by short-term S100A9 blockade improves
cardiac function after myocardial infarction. Eur Heart J. 2019 Aug

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