Dept. of Systems Biology and Bioinformatics is a part of the University of Rostock, Germany Universität Rostock

Ulf Schmitz

Image: Ulf Schmitz

Current Projects

Identification and functional analysis of microRNAs involved in malignant melanoma progression (MicroRna)
Cancer
MicroRNAs (miRNAs) are endogenous, small, non-coding ~22 nt RNA molecules that have emerged as a major class of regulatory genes for diverse range of biological functions. In our preliminary studies, we were able to demonstrate that primary melanoma show a distinct miRNA expression pattern compared with benign melanocytic nevi. The aim of the present project is to identify and functionally characterize miRNAs that might play a role during further melanoma progression (metastasis).
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Research Interest

miRNAs in malignant melanoma progression
„I am interested in miRNAs. I was able to associate miRNA targets with processes that can promote metastagenesis in malignant melanoma.“

MicroRNAs are ~21nt long molecules that have been found to regulate translation of target mRNAs in many cellular processes; tissue specific and in response to environmental changes. Malignant melanoma progression is one example for metastasis development that goes in hand with a characteristic expression profile of the miRNAome.
The question we focused on is: Which miRNAs are involved in the regulation of malignant melanoma progression and what are the key targets and their function?
It is particularly interesting to detect the mechanism how microRNAs choose their targets and what is the induced change in a particular cellular system. By answering these urgent questions the understanding of an entire cell regulatory machinery is at hand and previously unexpected cell physiological phenomena might become explainable.
We performed miRNA expression screens using qRT-PCR in samples of different disease states from melanoma patients. We examined state-of-the-art target prediction algorithms and finally selected high confidence predictions from their prediction intersection. Subsequently, we performed gene annotation enrichment analysis for GO terms, pathways and diseases.
A set of 14 miRNAs has been identified as significantly differentially expressed in metastasis vs. primary melanoma. Highly regulated target genes are tumour suppressors like PTEN. Targets released from miRNA induced repression are e.g. cell cycle regulators wee1 and CDKN1A. Further, an enrichment in translation regulation by melanoma metastamir where observed for pathways like apoptosis, MAPK signalling, proliferation, focal adhesion and angiogenesis.

Academic Background


Publications

Khan FM, Schmitz U, Nikolov S, Engelmann D, PĂŒtzer BM,Wolkenhauer O, Vera J
Hybrid modeling of the crosstalk between signaling and transcriptional networks using ordinary differential equations and multi-valued logic

BBA - Proteins and Proteomics, doi:10.1016/j.bbapap.2013.05.007, in press.
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Vera J, Schmitz U, Lai X, Engelmann D, Khan FM, Wolkenhauer O, PĂŒtzer BM (2013)
Kinetic modeling-based detection of genetic signatures that provide chemoresistance via the E2F1-p73/DNp73-miR-205 network

Cancer Research, doi:10.1158/0008-5472.CAN-12-4095
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Schmitz U, Wolkenhauer O, Vera J (eds.)
MicroRNA Cancer Regulation - Advanced Concepts, Bioinformatics and Systems Biology Tools

Series: Advances in Experimental Medicine and Biology, Vol. 774
Springer 2012. ISBN: 978-94-007-5589-5
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Bhattacharya A, Schmitz U, Wolkenhauer O, Schönherr M, Raatz Y, Kunz M (2012)
Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma

Oncogene, doi: 10.1038/onc.2012.324.
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Fuellen G, Dengjel J, Hoeflich A, Hoeijmakers J, Kestler H, Kowald A, Priebe S, Rebholz-Schuhmann D, Schmeck B, Schmitz U, Stolzing A, SĂŒhnel J, Wuttke D, Vera J (2012)
Systems Biology and Bioinformatics in Aging Research: A Workshop Report

Rejuvenation Research, Vol 15, No 6, doi: 10.1089/rej.2012.1360.
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Alla V, Kowtharapu BS, Engelmann D, Emmrich S, Schmitz U, Steder M, PĂŒtzer BM (2012)
E2F1 confers anticancer drug resistance by targeting ABC transporter family members and Bcl-2 via the p73/DNp73-miR-205 circuitry

Cell Cycle, 11:1
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Lai X, Schmitz U, Gupta S, Bhattacharya A, Kunz M, Wolkenhauer O, Vera J (2012)
Computational analysis of target hub gene repression regulated by multiple and cooperative miRNAs

Nucleic Acids Research, 40: 8818-8834.

open access

Schmitz U, Vera J
Computational microRNA biology

in: Encyclopedia of Systems Biology; Dubitzky W, Wolkenhauer O, Yokata H, Cho K-H (eds.); Springer 2012. ISBN-13: 9781441998620

Guebel DV, Schmitz U, Wolkenhauer O, Vera J (2012)
Analysis of cell adhesion during early stages of colon cancer based on an extended multi-valued logic approach

Molecular Biosystems 8(4):1230-1242

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Gupta S, Schmitz U
Bioinformatics Analysis of High-Throughput Experiments

in: Recent Trends in Biotechnology. Volume 2; Singh M P, Agrawal A, Sharma B (eds.); Nova Science Publishers 2011. ISBN: 9781617617973

Gupta SK, Gupta SK, Smita S, Srivastava M, Lai X, Schmitz U, Rahman Q, Wolkenhauer O, Vera J (2011)
Computational analysis and modeling the effectiveness of ‘Zanamivir’ targeting neuraminidase protein in pandemic H1N1 strains

Infection, Genetics and Evolution 11: 1072–1082

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Nikolov S, Vera J, Schmitz U, Wolkenhauer O (2011)
A model-based strategy to investigate the role of microRNA regulation in cancer signalling networks

Theory in Biosciences 130: 55-69
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Gupta SK, Srivastava M, Akhoon BA, Smita S, Schmitz U, Wolkenhauer O, Vera J, Gupta SK (2011)
Identification of immunogenic consensus T-cell epitopes in globally distributed influenza-A H1N1 neuraminidase

Infection, Genetics and Evolution 11: 308–319
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Raasch P, Schmitz U, Patenge N, Vera J, Kreikemeyer B, Wolkenhauer O (2010)
Non-coding RNA detection methods combined to improve usability, reproducibility and precision

BMC Bioinformatics 11: 491
open access 

Schultz J, Koczan D, Schmitz U, Ibrahim SM, Pilch D, Landsberg J, Kunz M (2010)
Tumor-promoting role of signal transducer and activator of transcription (Stat)1 in late-stage melanoma growth

Clinical & Experimental Metastasis 27: 133-140
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Vera J, Kwon T, Schmitz U, Kolch W, Wolkenhauer O (2009)
Exploration of homodimer receptor - homodimer protein interactions

International Journal of Bioinformatics Research and Applications 4: 447-457
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additional files

Hoffrogge R, Beyer S, HĂŒbner R, Mikkat S, Mix E, Scharf C, Schmitz U, Pauleweit S, Berth M, Zbrzycki IZ, Christoph H, Pahnke J, Wolkenhauer O, Uhrmacher A, Völker U, Rolfs R (2007)
2-DE profiling of GDNF overexpression-related proteome changes in differentiating ST14A rat progenitor cells

Proteomics 7: 33-46
open access

Raasch P, Schmitz U, Kreikemeyer B, Wolkenhauer O (2010)
Effective ncRNA detection

Rostocker Informatik-Berichte 32: 158-166
open access

Vera J, Kwon T, Schmitz U, Millat T, Wolkenhauer O
Bioinformatics analysis of interactions of receptor homodimers with intracellular protein homodimers

Rostocker Informatik-Berichte, 31, 2007

Schmitz U, Lai X, Vera J, Wolkenhauer O
The regulation of microRNA target hubs

International Workshop on Small RNA in Cancer, Inflammation, and Aging, Copenhagen (Denmark), September 3 - 4 , 2012.

Lai X, Schmitz U, Vera J, Wolkenhauer O
A systems biology approach to study the cellular function of microRNAs

International Workshop on Small RNA in Cancer, Inflammation, and Aging, Copenhagen (Denmark), September 3 - 4, 2012.

Guebel DV, Schmitz U, Wolkenhauer O, Vera J
AnĂĄlisis de los fenĂłmenos de adhesiĂłn celular en los estadios tempranos de cĂĄncer de colon mediante un modelo de lĂłgica multi-valuada extendida

XXVII Jornadas Multidisciplinarias de Oncológia des Instituto “Angel H. Roffo”. Buenos Aires (Argentina), 13-16 September, 2011

 

Lai X, Schmitz U, Gupta S, Kunz M, Wolkenhauer O, Vera J
On the regulation of microRNA target hubs: a Systems Biology perspective

12th International Conference on Systems Biology (ICSB), Heidelberg/Mannheim, Germany, 28 August - 1 September 2011

Bhattacharya A, Schmitz U, Schonherr M, Raatz Y, Kunz M
Role of micro RNA 372 in melanoma progression

Experimental Dermatology (2011), Volume 20, Issue 2, 196.

Guebel DV, Schmitz U, Wolkenhauer O, Vera J
An extensive Boolean network for analysing the signalling events in early stages of humen colon cancer

11th International Conference on Systems Biology (ICSB), Edinburgh, October 2010.

Schmitz U, Bhattacharya A, Gupta S, Schultz J, Kunz M, Wolkenhauer O
MicroRNAs in malignant melanoma progression

German Conference on Bioinformatics, Braunschweig, Germany, 2010

Raasch P, Schmitz U, Patenge N, Vera J, Kreikemeyer B, Wolkenhauer O
Local Genomic Properties as Indicators of Functional Elements

3. Gemeinsame Tagung der DGHM und der VAAM, Hannover, Germany, 28.03.-31.03.2010

Stalidzans E, Mozga I, Roos C, Fernandez E, Font J, Vanags J, Remm M, Schmitz U, Wolkenhauer O
Modular education for interdisciplinary Systems Biology

9th International Conference on Systems Biology, Gothenburg, 2008.

Raasch P, Schmitz U, Kreikemeyer B, Wolkenhauer O
A JAVA framework to integrate ncRNA detection methods

Systems Biology for Medical Applications Summer School, Costa Adeje, Spain, 2008.

Vera J, Millat T, Kwon T, Schmitz U, Wolkenhauer O
Exploring cell signalling homodimer receptor-homodimer protein interactions and their dynamical consequences

German Conference on Bioinformatics, Potsdam (Germany), 26 September - 28 September 2007

Contact Details

Systems Biology and Bioinformatics
Ulmenstrasse 69 (building 3, 3rd floor)
18057 Rostock, Germany
Room 415a

+49 381 498-7576
+49 381 498-118 7572
ulf.schmitz(at)uni-rostock.de

Collaborators & Partners

University of Rostock
Rostock/Germany
Prof. Manfred Kunz
Department of Dermatology, Venereology and Allergology, University of Leipzig, Leipzig/Germany
Prof. Brigitte PĂŒtzer
Department of Vectorology and Experimental Gene Therapy; Biomedical Research Center; Rostock University Medicine
Prof. Dr. Svetoslav Nikolov
Institute of Mechanics and Biomechanics (BAS), Sofia/Bulgaria
CSIR-Indian Institute of Toxicology Research
Lucknow, India