Kliniken & Institute … Kliniken Zentrum für Innere… Innere Medizin V:… Forschung Research Group Dietrich…

An integrated SYstems Medicine approach to Personalized And targeted THerapy in lYmphoma (SYMPATHY)

We are a Partner group of the European Molecular Biology Laboratory (EMBL) within the Molecular Medicine Partnership Unit (MMPU):

Our aim is to bring biology-based individualized treatment of lymphoma and leukemia into clinical practice. To achieve this ambitious aim, we establish a systems medicine program that integrates systematic functional assays, multi-omic profiling, bioinformatic analysis, mathematical modeling and setup towards a clinical exploitation. The basis of the program is a platform to map patient specific pathway activity and drug sensitivity of their primary tumor cells ex-vivo. By comparing drug responses across patients with detailed molecular characterization (e.g. whole exome- and RNA-sequencing) and the clinical parameters, we obtain a rich set of associations of drug sensitivity with biology, biomarkers and outcome. 

Figure 1) The general layout of our research program.

A particular focus of our research is on signals provided by the microenvironment, and  how these signals modify pathway activities targeted by drugs. We aim to generate a systems-level understanding of how the microenvironment and the individual genetic and molecular make-up of a tumor interact and modify drug response using a high throughput automated microscopy platform mimicking microenvironment conditions. In parallel, we investigate further dimensions of in-vivo drug response (3D-space, timing of drug response) with a hierarchy of increasingly complex culture models and readouts in suitable tumors.

Our group is funded by the eMed Programm of the BMBF. (http://www.sys-med.de/de/)

Group Members

Wiss. Mitarbeiter/-innen



Med.-techn. Assistentin

Selected Publication:

Drug-perturbation-based stratification of blood cancer. 
Dietrich S, Oleś M, Lu J, Sellner L, Anders S, Velten B, Wu B, Hüllein J, da Silva Liberio M, Walther T, Wagner L, Rabe S, Ghidelli-Disse S, Bantscheff M, Oleś AK, Słabicki M, Mock A, Oakes CC, Wang S, Oppermann S, Lukas M, Kim V, Sill M, Benner A, Jauch A, Sutton LA, Young E, Rosenquist R, Liu X, Jethwa A, Lee KS, Lewis J, Putzker K, Lutz C, Rossi D, Mokhir A, Oellerich T, Zirlik K, Herling M, Nguyen-Khac F, Plass C, Andersson E, Mustjoki S, von Kalle C, Ho AD, Hensel M, Dürig J, Ringshausen I, Zapatka M, Huber W, Zenz T. 
J Clin Invest. 2018 Jan 2;128(1):427-445. doi: 10.1172/JCI93801. Epub 2017 Dec 11.PMID:29227286

Multi-Omics factor analysis disentangles heterogeneity in blood cancer 
Ricard Argelaguet, Britta Velten, Damien Arnol, Sascha Dietrich, Thorsten Zenz, John C. Marioni, Florian Buettner, Wolfgang Huber, Oliver Stegle 
bioRxiv beta Nov. 10, 2017 doi.org/10.1101/217554

BRAF inhibition in hairy cell leukemia with low-dose vemurafenib. 
Dietrich S, Pircher A, Endris V, Peyrade F, Wendtner CM, Follows GA, Hüllein J, Jethwa A, Ellert E, Walther T, Liu X, Dyer MJ, Elter T, Brummer T, Zeiser R, Hermann M, Herold M, Weichert W, Dearden C, Haferlach T, Seiffert M, Hallek M, von Kalle C, Ho AD, Gaehler A, Andrulis M, Steurer M, Zenz T. 
Blood. 2016 Jun 9;127(23):2847-55. doi: 10.1182/blood-2015-11-680074. 
PMID: 26941398

Recurrent CDKN1B (p27) mutations in hairy cell leukemia. 
Dietrich S, Hüllein J, Lee SC, Hutter B, Gonzalez D, Jayne S, Dyer MJ, Oleś M, Else M, Liu X, Słabicki M, Wu B, Troussard X, Dürig J, Andrulis M, Dearden C, von Kalle C, Granzow M, Jauch A, Fröhling S, Huber W, Meggendorfer M, Haferlach T, Ho AD, Richter D, Brors B, Glimm H, Matutes E, Abdel Wahab O, Zenz T. 
Blood. 2015 Aug 20;126(8):1005-8. doi: 10.1182/blood-2015-04-643361. 
PMID: 26065650

Orchestrating high-throughput genomic analysis with Bioconductor. 
Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, Bravo HC, Davis S, Gatto L, Girke T, Gottardo R, Hahne F, Hansen KD, Irizarry RA, Lawrence M, Love MI, MacDonald J, Obenchain V, Oleś AK, Pagès H, Reyes A, Shannon P, Smyth GK, Tenenbaum D, Waldron L, Morgan M. 
Nat Methods. 2015 Feb;12(2):115-21. doi: 10.1038/nmeth.3252. Review. 
PMID: 25633503

Continued response off treatment after BRAF inhibition in refractory hairy cell leukemia. 
Dietrich S, Hüllein J, Hundemer M, Lehners N, Jethwa A, Capper D, Acker T, Garvalov BK, Andrulis M, Blume C, Schulte C, Mandel T, Meissner J, Fröhling S, von Kalle C, Glimm H, Ho AD, Zenz T. 
J Clin Oncol. 2013 Jul 1;31(19):e300-3. doi: 10.1200/JCO.2012.45.9495. No abstract available. 

BRAF inhibition in refractory hairy-cell leukemia. 
Dietrich S, Glimm H, Andrulis M, von Kalle C, Ho AD, Zenz T. 
N Engl J Med. 2012 May 24;366(21):2038-40. doi: 10.1056/NEJMc1202124.