CURRICULUM VITAE JOHANNES RAINER

CURRENT ADDRESS Center for Biomedicine EURAC reseach Via Galvani 31 39100 Bolzano, Italy Phone: +39 0471 055491 E-mail: [email protected]

PERSONAL Date of birth: Place of birth: Marital status: Citizenship: Married to: Children: Paternity leave:

January 18, 1977 Brixen, Italy married Italian Anita Domanegg 2 24.09.2012-25.05.2013

LANGUAGES German English Italian EDUCATION November 2007

November 2003

PhD thesis defense, Rigorosum (degree with distinction) Thesis title: Identification of glucocorticoid regulated microRNAs in human acute lymphoblastic leukemia cells. Ph.D. student at the Institute of Genomics and Bioinformatics, Graz University of Technology in cooperation with Tyrolean Cancer Institute, Innsbruck, Austria. Special subjects: Bioinformatics, Biostatistics, Acute Lymphoblastic Leukemia.

Curriculum Vitae: Johannes Rainer

1996 - 2003

Study of electrical engineering (master’s program) at Graz University of Technology, Graz, Austria Specialization in Biomedical Engineering. July 2002 - February 2003: Master thesis at the Institute of Biomedical Engineering, Graz University of Technology, Graz, Austria: Web Interface for large scale Microarray Analysis. October, 2003: Second diploma October, 2003: Graduation to: Master of Science (Diplom Ingenieur).

1991 - 1996

High School (Realgymnasium), Brixen, Italy.

1988 - 1991

Secondary School (Mittelschule), Brixen, Italy.

1983 - 1988

Primary School (Grundschule), Brixen, Italy.

PROFESSIONAL EXPERIENCE 2015 - present

Senior researcher at the Center for Biomedicine, EURAC research, Bolzano, Italy

Feb 2009 - 2015

Bioinformatic junior group leader (Univ. Ass.) at the Division of Molecular Pathophysiology, Biocenter, Medical University Innsbruck, Innsbruck, Austria.

Nov 2007 - Feb 2009

Postdoc, Acute Lymphoblasti Leukemia Group at the Tyrolean Cancer Research Institute, Innsbruck, Austria.

SCIENTIFIC AND ANALYTICAL EXPERIENCE Highly experienced in the analysis and quality assessments of microarray data including high density microarrays (Affymetrix Exon 1.0 and Gene ST) and ChIP-chip data sets. In silico prediction of transcription factor binding sites on DNA sequences. Prediction of microRNA host genes (i.e. primary transcription units) and microRNA target sites. Analysis of high throughput sequencing data (ChIP-seq, RNA-seq). Support in experimental design, supervision and conduction of quality assessments and analysis of gene expression experiments performed at the Expression Profiling Unit (Affymetrix Core Facility) of the Medical University Innsbruck; responsible for the bioinformatic analysis of microarray data sets generated in the Expression Profiling Unit. Performed over 90 bioinformatic/biostatistic data analyses of microarray or other whole genome data sets.

SOFTWARE AND METHOD DEVELOPMENTS

Curriculum Vitae: Johannes Rainer

Perl scripts to enable automated Affymetrix Exon, Gene ST and Promoter Tiling Microarray probe sequence alignments and generation of custom annotations (including CDF files) and development of methods for the analysis thereof. Prediction of microRNA host genes based on genomic localization of microRNA precursors. FloWeb: web based analysis and data management system for flow cytometry data.

CARMAweb: web based analysis suite for the analysis of microarray data (https://carmaweb.genome.tugraz Developer and maintainer of two R-software packages (maDB and pgUtils) part of the open source software project Bioconductor (http://www.bioconductor.org). Other R, Perl, Python and Java software packages and scripts for annotation, data visualisation, data pre-processing, protein-protein-interaction data analysis, transcription factor binding analysis etc.

SCIENTIFIC REVIEWER FOR BMC Genomics BMC Research Letters FEBS Letters PLOS ONE

TEACHING Medical University Innsbruck, core courses for MCBO PhD program (since SS 2008): Genomics: Expression Profiling (1 SSt); LVNr: 040004 (WS), 040505 (SS). Genomics: Bioinformatics (1 SSt); LVNr: 040016 (WS), 040516 (SS). Co-supervision of 3 Bachelor students in Bioinformatics at the UMIT (Simone Ecker, Philippe Thomas, Markus Unterwurzacher). Supervision of one Master’s student in Bioinformatics at the UMIT (Simone Ecker), co-supervision of 2 Master’s students in Bioinformatics at the UMIT (Simon Schafferer, Benjamin Weidenholzer). Co-supervision of 2 MCBO PhD students at the Medical University Innsbruck (Daniel Bindreither: Jan 2010 - Jun 2014; Tatsiana Aneichyk: May 2012 - present).

Curriculum Vitae: Johannes Rainer

GRANTS 2010-2012

Co-project leader in Oncotyrol project: Title: 5.3: Defining the glucocorticoid-responsive transcriptome in the lymphoid lineage by advanced expression profiling technology - Part II: Bioinformatics and Identification of molecular signatures for acute lymphoblastic leukemia patient classification/stratification. Financial support: 139,000 e (total project costs including in-kinds: 273,000 e).

2010-2012

Principal investigator of OncoSTART project (internationally reviewed): Title: Identification of molecular signatures for acute lymphoblastic leukemia patient classification/stratification Financial support: 50,000 e (total project costs including in-kinds: 100,000 e). Note: this grant has been integrated into the Oncotyrol project 5.3 listed above. ¨ Osterreichische Krebshilfe-KG/Tirol Title: Modelling glucocorticoid treatment response in childhood acute lymphoblastic leukaemia patients by integrating active glucocorticoid levels, lymphoblast counts and gene expression data Financial support: 5,000 e.

2011

2010

¨ Osterreichische Krebshilfe-KG/Tirol Title: Comparing the ex vivo and in vivo transcriptional response of acute lymphoblastic leukemia cells to glucocorticoid treatment Financial support: 5,000 e.

2009

¨ Osterreichische Krebshilfe-KG/Tirol Title: Identification and verification of alternative transcript isoforms and alternative splice events in glucocorticoid treated acute lymphoblastic leukemia cells Financial support: 3,727 e.

2008

¨ Osterreichische Krebshilfe-KG/Tirol Title: Revealing the function of glucocorticoid regulated microRNAs in acute lymphoblastic leukemia cells and their involvement in GC induced apoptosis Financial support: 3,980 e

2007

¨ Osterreichische Krebshilfe-KG/Tirol Title: Erweiterungen der TKFI Tumor-Genexpressionsdatenbank: microRNA Microarrays, automatische Annotations-Aktualisierung und ProbesetQualit¨ atsbestimmung Financial support: 5,610 e

Curriculum Vitae: Johannes Rainer

2006

¨ Osterreichische Krebshilfe-KG/Tirol Title: Entwicklung bioinformatischer Werkzeuge zur Verwaltung von TumorGenexpressionsdatenbanken Financial support: 4,750 e

2005

¨ Osterreichische Krebshilfe-KG/Tirol Title: Entwicklung bioinformatischer Werkzeuge zur Analyse von Genexpressionsprofilen maligner Zellen Financial support: 3,675 e

PUBLICATIONS Number of publications

31 (28 original papers) (2 reviews) (1 book chapter)

Impact factor points (2014):

194.75 (total) 32.4 (first, corresponding or last author)

Published articles [1] Bu H, Narisu N, Schlick B, Rainer J, Manke T, Sch¨afer G, Pasqualini L, Chines P, Schweiger MR, Fuchsberger C, Klocker H. Putative Prostate Cancer Risk SNP in an AR Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in AR Target Sites. Hum Mutat. 2015 Sep 28. [Epub Sept 2015]. [2] Nicholson L, Evans CA, Matheson E, Minto L, Keilty C, Sanichar M, Case M, Schwab C, Williamson D, Rainer J, Harrison CJ, Kofler R, Hall AG, Redfern CP, Whetton AD, Irving JA. Quantitative proteomic analysis reveals maturation as a mechanism underlying glucocorticoid resistance in B lineage ALL and re-sensitization by JNK inhibition. Br J Haematol. 2015 Aug 27. [Epub Aug 2015]. [3] Fava LL, Rainer J, Haschka MD, Geley S, Villunger A. Beclin 1 is dispensable for chromosome congression and proper outer kinetochore assembly. EMBO Rep. 2015 Oct;16(10):1233-6. [4] Pasqualini L, Bu H, Puhr M, Narisu N, Rainer J, Schlick B, Sch¨afer G, Angelova M, Trajanoski Z, B¨ orno ST, Schweiger MR, Fuchsberger C, Klocker H. miR-22 and miR29a Are Members of the Androgen Receptor Cistrome Modulating LAMC1 and Mcl-1 in Prostate Cancer. Mol Endocrinol. 2015 Jul;29(7):1037-54. [5] Salcher S, Hagenbuchner J, Geiger K, Seiter MA, Rainer J, Kofler R, Hermann M, Kiechl-Kohlendorfer U, Ausserlechner MJ, Obexer P. C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma. Mol Cancer. 2014 Sep 28;13(1):224. [6] Bindreither D, Ecker S, Gschirr B, Kofler A, Kofler R, Rainer J† . The synthetic glucocorticoids prednisolone and dexamethasone regulate the same genes in acute lymphoblastic leukemia cells. BMC Genomics. 2014 Aug 7;15:662. [7] Spilka R, Ernst C, Bergler H, Rainer J, Flechsig S, Vogetseder A, Lederer E, Benesch M, Brunner A, Geley S, Eger A, Bachmann F, Doppler W, Obrist P, Haybaeck J. eIF3a is over-expressed in urinary bladder cancer and influences its phenotype independent of

Curriculum Vitae: Johannes Rainer

translation initiation. Cell Oncol. Epub Jul 2014. [8] Hoefer J, Kern J, Ofer P, Eder IE, Sch¨afer G, Dietrich D, Kristiansen G, Geley S, Rainer J, Gunsilius E, Klocker H, Culig Z, Puhr M. SOCS2 correlates with malignancy and exerts growth promoting effects in prostate cancer. Endocr Relat Cancer. 2014;21:175-187. Epub Nov 2013. [9] Aneichyk T, Bindreither D, Mantinger C, Grazio D, Goetsch K, Kofler R, Rainer J† . Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation. BMC Genomics. 2013 Dec 1;14(1):844. [10] Martowicz A, Rainer J, Lelong J, Spizzo G, Gastl G, Untergasser G. EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth. Mol Cancer. 2013 Jun 10;12(1):56. [11] Hanada T, Weitzer S, Mair B, Bernreuther C, Wainger BJ, Ichida J, Hanada R, Orthofer M, Cronin SJ, Komnenovic V, Minis A, Sato F, Mimata H, Yoshimura A, Tamir I, Rainer J, Kofler R, Yaron A, Eggan KC, Woolf CJ, Glatzel M, Herbst R, Martinez J, Penninger JM. CLP1 links tRNA metabolism to progressive motor-neuron loss. Nature. 2013 Mar 28;495(7442):474-80. [12] Mahlknecht P, Stemberger S, Sprenger F, Rainer J, Hametner E, Kirchmair R, Grabmer C, Scherfler C, Wenning GK, Seppi K, Poewe W, Reindl M. An antibody microarray analysis of serum cytokines in neurodegenerative Parkinsonian syndromes. Proteome Sci. 2012 Nov 23;10(1):71; Epub. [13] Mikolcevic P, Rainer J, Geley S. Orphan kinases turn eccentric: A new class of cyclin Y-activated, membrane-targeted CDKs. Cell Cycle. 2012 Oct 15;11(20):3758-68. Epub 2012 Aug 16. [14] Goebel G, Berger R, Strasak AM, Egle D, M¨ uller-Holzner E, Schmidt S, Rainer J, Presul E, Parson E, Lang S, Jones A, Widschwendter M, Fiegl H. Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients. Br J Cancer. 2012 Jan3;106(1):189-98. Epub 2011 Nov 22. [15] Rainer J† , Lelong J, Bindreither D, Mantinger C, Ploner C, Geley S, Kofler R. Research Resource: Transcriptional Response to Glucocorticoids in Childhood Acute Lymphoblastic Leukemia. Mol Endocrinol. 2012 Jan;26(1):178-93. Epub 2011 Nov 10. [16] Oppl B, Kofler A, Schwarz S, Rainer J† , Kofler R. Establishing a sensitive and specific assay for determination of glucocorticoid bioactivity. Wiener Klin Wochenschr. 2011 Apr;123(7-8):222-229. [17] Sanchez-Cabo F, Rainer J, Dopazo A, Trajanoski Z and Hackl H. Insights into global mechanisms and disease by gene expression profiling. Methods Mol Biol. 2011;719:26998. [18] Kuster L, Grausenburger R, Fuka G, Kaindl U, Krapf G, Inthal A, Mann G, Kauer M, Rainer J, Kofler R, Hall A, Metzler M, Meyer LH, Meyer C, Harbott J, Marschalek R, Strehl S, Haas OA and Panzer-Gr¨ umayer R. ETV6/RUNX1-positive relapses evolve from an ancestral clone and frequently acquire deletions of genes implicated in glucocorticoid signaling. Blood. 2011 Mar 3;117(9):2658-67. [19] Prokudin I, Stasyk T, Rainer J, Bonn GK, Kofler R and Huber LA. Comprehensive proteomic and transcriptomic characterization of hepatic expression signatures affected in p14 liver conditional knockout mice. Proteomics. Feb;11(3):469-80.

Curriculum Vitae: Johannes Rainer

[20] Eberhart K, Rainer J, Bindreither D, Ritter I, Gnaiger E, Kofler R, Oefner PJ and Renner K. Glucocorticoid-induced alterations in mitochondrial membrane properties and respiration in childhood acute lymphoblastic leukemia. BBA Bioenergetics. 2011 Jun;1807(6):719-25. [21] Carlet M, Janjetovic K, Rainer J, Schmidt S, Panzer-Grumeyer R, Mann G, Prelog M, Meister B, Ploner C and Kofler R. Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells. B MC Cancer. 2010 Nov 23;10(1):638. [22] Wasim M, Carlet M, Mansha M, Greil R, Ploner C, Trockenbacher A, Rainer J and Kofler R. PLZF/ZBTB16, a glucocorticoid response gene in acute lymphoblastic leukemia, interferes with glucocorticoid-induced apoptosis. J Steroid Biochem Mol Biol. 2010 Jun;120(4-5):218-27. [23] Mansha M, Carlet M, Ploner C, Gruber G, Wasim M, Wiegers GJ, Rainer J, Geley S and Kofler R. Functional analyses of Src-like adaptor (SLA), a glucocorticoid-regulated gene in acute lymphoblastic leukemia. Leuk Res. 2010 Apr;34(4):529-34. [24] Ploner C, Rainer J, Lobenwein S, Geley S and Kofler R. Repression of the BH3only molecule PMAIP1/Noxa impairs glucocorticoid sensitivity of acute lymphoblastic leukemia cells. Apoptosis. 2009 Jun;14(6):821-8. [25] Rainer J, Ploner C, Jesacher S, Ploner A, Eduardoff M, Mansha M, Wasim M, Panzer-Gr¨ umayer R, Trajanoski Z, Niederegger H and Kofler R. Glucocorticoidregulated microRNAs and mirtrons in acute lymphoblastic leukemia. Leukemia, 2009 Apr;23(4):746-52. [26] Ploner C, Rainer J, Niederegger H, Eduardoff M, Villunger A, Geley S, Kofler R. The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia. Leukemia, 2008 Feb ; 22(2): 370-7. [27] Rainer J, Sanchez-Cabo F, Stocker G, Sturn A and Trajanoski Z. CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis. N ucleic Acids Res, 2006. 34(Web Server Issue):W498-503. [28] Schmidt S, Rainer J, Riml S, Ploner C, Jesacher S, Achmuller C, Presul E, Skvortsov S, Crazzolara R, Fiegl M, Raivio T, Janne O A, Geley S, Meister B, Kofler R. Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia. B lood, 2006. 107(5):2061-2069. [29] Ploner C, Schmidt S, Presul E, Renner K, Schrocksnadel K, Rainer J, Riml S and Kofler R. Glucocorticoid-induced apoptosis and glucocorticoid resistance in acute lymphoblastic leukemia. J Steroid Biochem Mol Biol, 2005. 93(2-5):153-160. [30] Schmidt S, Rainer J, Ploner C, Presul E, Riml S and Kofler R. Glucocorticoidinduced apoptosis and glucocorticoid resistance: molecular mechanisms and clinical relevance. C ell Death Differ, 2004. 11 Suppl 1:S45-55. [31] Sturn A, Mlecnik B, Pieler R, Rainer J, Truskaller T, Trajanoski Z. Client-Server Environment for High-Performance Gene Expression Data Analysis. B ioinformatics, 2003. 19:772-773. †: Corresponding author

Curriculum Vitae: Johannes Rainer

Bozen, October 12, 2015

Johannes Rainer

Curriculum Vitae: Johannes Rainer