Walter J. Jessen Curriculum Vitae OFFICE ADDRESS Biomarker Center of Excellence Office (317) 467-7398 | Cell (317) 292-4739 Covance Laboratories, Inc. e-mail: walter@walterjessen.com 671 South Meridian Road Website: http://www.walterjessen.com Greenfield, IN 46140 EDUCATION Ph.D., Molecular Biology, Department of Biochemistry and Biophysics, Texas A&M University, 1998 - 2004. B.S., Physics, Department of Chemistry and Physics, Purdue University Calumet, 1992 - 1998. PROFESSIONAL AND RESEARCH EXPERIENCE Computational Biologist, 2010 - Present. Covance Laboratories, Inc., Biomarker Center of Excellence Responsible for designing, implementing and applying cutting edge computational methods to assemble, integrate, analyze and interpret data from a wide variety of sources including clinical data, literature and high-throughput genomic or proteomic platforms. Works closely with scientists, clinicians, statisticians and software engineers to support the discovery and application of biomarkers in the clinical setting. Routinely interacts with colleagues to mine, analyze and interpret complex biological data. Knowledge Curator, 2010 - Present. Biomarker Commons, http://biomarkercommons.org Continually identifies, aggregates, filters, organizes, contextualizes and shares the most relevant news and research content on biomarkers. Builds custom data feeds to manipulate data from external sources. Manages various types of user communications tools (email subscriptions, RSS, Mendeley, Twitter). Built and administrates the site using the Drupal content management system. Research Associate, laboratory of Nancy Ratner, 2008 - 2010. Cincinnati Children's Hospital Medical Center, Division of Experimental Hematology and Cancer Biology. Responsible for developing data resources that will allow the use of a variety of statistical and biological analysis approaches to evaluate microarray data, as well as additional data related to variations in disease severity, histological patterns and proteomic data being collected from both mouse animal models of neurofibromatosis type 1 (NF1), individual human neurofibromas and malignant peripheral nerve sheath tumors. Collaborate with other Principle Investigators of the Neurofibromatosis Microarray and Systems Biology Consortium (http://nf1.cchmc.org) to develop bioinformatics analyses to understand the molecular mechanisms by which tumors form and progress with the ultimate goal of developing treatment strategies. Postdoctoral Research Fellow, laboratory of Bruce J. Aronow, 2004 - 2007. Cincinnati Children's Hospital Medical Center, Division of Biomedical Informatics. Utilized transcriptional regulatory and gene interaction networks, cancer biology and embryonic and postnatal development in human and mouse models to inform and characterize biological states, disease processes and developmental disorders. Performed functional and comparative genomics on microarray data, and utilized histologic patterns and clinical information to develop a systems biology approach that can be applied to a range of genetic diseases. Graduate Research Assistant, laboratory of Michael P. Kladde, 1998 - 2004. Texas A&M University, Department of Biochemistry and Biophysics. Developed a kinetic approach for analysis of chromatin remodeling in vivo, demonstrating that nucleosomes proximal to the transactivator binding site are remodeled earlier than those more distal. Developed an in vivo single molecule assay that identifies multiple promoter classes and supports a probabilistic model in which chromatin remodeling at PHO5 spreads from sites of transactivator binding and attenuates with distance. Bioengineered inducible DNA methyltransferase systems for the in vivo detection of chromatin structural changes, targeted methylation and factor footprints. PUBLICATIONS Keng VW, Rahrmann EP, Watson AL, Tschida BR, Moertel CL, Jessen WJ, Collins MH, Ratner N and Largaespada DA. Conditional inactivation of Pten and Nf1 in Schwann cells results in a severe peripheral nervous system phenotype and transformation. Submitted. Jessen WJ, Miller SJ, Wu J, Rizvi TA, Eaves D, Jousma E, Widemann B, Kim M, Dombi E, Dudley AH, Niwa-Kawakita M, Page GP, Giovannini M, Aronow BJ, Cripe TP, and Ratner N. Comprehensive cross-species analysis of neurofibroma and MPNST and preclinical testing validate Ras-MAPK signaling as a molecular therapeutic target for NF1 tumors. Submitted. Comstock CES, Augello MA, Schiewer MJ, Karch J, Burd CJ, Ertel A, Knudsen ES, Jessen WJ, Aronow BJ, Knudsen KE. JBC. Cyclin D1 is a Selective Modifier of Androgen-dependent Signaling and Androgen Receptor Function. J Biol Chem. 2011 Mar 11;286(10):8117-27. Epub 2011 Jan 5. Hummel TR, Jessen WJ, Miller SJ, Kluwe L, Mautner VF, Wallace MR, Lazaro C, Page GP, Worley PF, Aronow BJ, Schorry EK, Ratner N. Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clin Cancer Res. 2010 Oct 15;16(20):5048-57. Epub 2010 Aug 25. *Miller SJ, *Jessen WJ, Mehta T, Hardiman A, Sites E, Kaiser S, Jegga A, Li H, Upadhyaya M, Giovannini M, Muir D, Wallace MR, Lopez E, Serra E, Nielsen GP, Lazaro C, Stemmer-Rachamimov A, Page G, Aronow BJ and Ratner N. Integrative genomic analyses of neurofibromatosis tumors identify SOX9 as biomarker and survival gene. *These authors contributed equally to this work. EMBO Mol Med. 2009, 1(4):236-248. Shen H, Powers N, Saini N, Comstock CE, Sharma A, Weaver K, Revelo MP, Gerald W, Williams E, Jessen WJ, Aronow BJ, Rossen G, Weissman B, Murchardt C, Yaniv M and Knudsen KE. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res. 2008, 68(24):10154-10162. Ouyang X, Jessen WJ, Al-Ahmadie H, Serio AM, Lin Y, Shih WJ, Reuter VE, Scardino PT, Shen MM, Aronow BJ, Vickers AJ, Gerald WL and Abate-Shen C. Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer. Cancer Res. 2008, 68(7):2132-2144. Banach-Petrosky W, Jessen WJ, Ouyang X, Gao H, Rao J, Quinn J, Aronow BJ and Abate-Shen C. Prolonged exposure to reduced levels of androgen accelerates prostate cancer progression in Nkx3.1; Pten mutant mice. Cancer Res. 2007, 67(19):9089-9096. Liu X, Jessen WJ, Sivaganesan S, Aronow BJ and Medvedovic M. Bayesian hierarchical model for transcriptional module discovery by jointly modeling gene expression and ChIP-chip data. BMC Bioinformatics. 2007, 8:283. Kaiser S, Park Y, Franklin J, Halberg RB, Yu M, Jessen WJ, Freudenberg J, Chen X, Haigis K, Jegga A, Kong S, Sakthivel B, Xu H, Reichling T, Azhar M, Roberts RB, Bissahoyo AC, Gonzales F, Bloom G, Eschrich S, Aronow J, Kleimeyer J, Kleimeyer M, Ramaswamy V, Settle SH, Levy S, Graff JM, Doetschman T, Groden JL, Dove WF, Threadgill DW, Yeatman T, Coffey Jr RJ and Aronow BJ. Identification by mouse models comparison of gene expression modules that recapitulate development and promote oncogenesis in human colon cancer. Genome Biol. 2007, 8(7):R131. Jessen WJ, Hoose SA, Kilgore JA and Kladde MP. Active PHO5 chromatin encompasses a variable number of nucleosomes at individual promoters. Nat Struct Mol Biol. 2006, 13(3):256-263. Jessen WJ, Dhasarathy A, Hoose SA, Carvin CD, Risinger AL and Kladde MP. Mapping chromatin structure in vivo using DNA methyltransferases. Methods. 2004, 33(1):68-80. Carvin CD, Dhasarathy A, Friesenhahn LB, Jessen WJ and Kladde MP. Targeted cytosine methylation for in vivo detection of protein-DNA interactions. Proc Natl Acad Sci USA. 2003, 100(13):7743-7748. Comstock CES, Burd CJ, Jessen WJ and Knudsen KE: Gene profiling analysis of androgen receptor mediated function. In Contemporary Endocrinology: Genomics in Endocrinology, DNA Microarray Analysis in Endocrine Health and Disease. Edited by Handwerger S and Aronow B. New Jersey: Humana Press Inc.; 2007:36. Kilgore JA, Hoose SA, Dhasarathy A, Neef DW, Jessen WJ and Kladde MP: Dynamic chromatin remodeling at the budding yeast PHO5 promoter. In DNA Structure, Chromatin and Gene Expression. Edited by Kiyama R and Shimizu M. India: Research Signpost, 2007:101-120. BIOINFORMATIC AND COMPUTATIONAL SKILLS SUMMARY Proficient at interpreting biological data and translating research results into understandable language and formats. Knowledgeable in data/text mining from a variety of sources, including clinical data, literature and high-throughput genomic or proteomic platforms. Skilled at integrating disparate types of data. Proficient with gene expression and pathway analysis using the following software packages: MetaCore (GeneGo), Ingenuity Pathway Analysis (Ingenuity Systems), GeneSpring GX (Agilent Technologies), Database for Annotation, Visualization and Integrated Discovery 2008 functional annotation tools (National Institute of Allergy and Infectious Diseases), GATACA, ToppGene and Genome TraFac (Cincinnati Children's Hospital). Proficient with network visualization and analysis using the following software packages: Cytoscape, MetaCore (GeneGo) and Ingenuity Pathways Analysis (Ingenuity Systems). Knowledgeable in the mechanics and application of a number of statistical tests for the analysis of gene expression data, including T-Test, Welch ANVOA, Kruskal-Wallis non-parametric test, Fisher's Exact Test, Benjamini and Hochberg False Discovery Rate and Kaplan-Meier survival analysis. Proficient in genomic analysis, including supervised and unsupervised multivariate analyses, comparative genomics and pathway modeling. Adapt with sample classification, i.e., class comparison, class prediction and class discovery. Proficient in aligning data sets between experiments and platforms and across species. Statistical Analysis Software: knowledgeable with R language for Statistical Computing/Bioconductor, basic experience with SPSS and Matlab. Database: MySQL. Programming: familiar with Perl. Internet technologies/languages: Apache web server, HTML, CSS, PHP, XML. Platforms: Mac OS X, Windows, Linux and UNIX. MOLECULAR BIOLOGY SKILLS SUMMARY DNA and RNA extraction. Northern and southern blotting; radioactive/fluorescence-based DNA sequencing; extensive experience with primer extension analysis. RT-PCR. Fluorescence microscopy. Extensive experience with recombinant DNA techniques, site directed mutagenesis, vector construction, primer design, PCR, and restriction analysis. Extensive experience with yeast genetic techniques including tetrad dissection, transformation, gene replacement/deletion, expression techniques, genomic DNA purification, plasmid rescue, total RNA purification, and yeast acid phosphatase assays. Bacterial genetic techniques including phage lysate preparation, P1 phage transduction, conjugation, transformation, and mini- and maxi-prep plasmid DNA purification. Chromatin immunoprecipitation (ChIP). Extensive experience with chromatin footprinting/remodeling assays utilizing in vivo expressed cytosine-5 DNA methyltransferases; extensive experience with detection of cytosine-5 DNA methylation by bisulfite genomic sequencing. Yeast nuclei and spheroplast preparation. INVITED SEMINARS Covance BioPathways for Biomarker Discovery - Biomarker Discovery: moving diagnostics to the forefront of medical research, Indiana Health Industry Forum, Indianapolis, Indiana, 2011. - The ADAPT 2011 Congress, Biomarker Discovery Informatics, Philadelphia, Pennsylvania, 2011. Integrative Genomic Approaches to Identify Biomarkers and Therapeutic Targets in NF1 - Covance Biomarker Center of Excellence, Greenfield, Indiana, 2010. Host: Tom Turi. - Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 2009. Host: Nancy Ratner. NF1: Timing and Targets - The 2008 Neurofibromatosis Conference, Cincinnati Children's Hospital, Cincinnati, Ohio, 2008. Toward a Molecular Model of Disease Progression in Atrial Fibrillation. - The Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio, 2007. Host: Arnold Schwartz. Bidirectional Propagation of Chromatin Remodeling During Transcriptional Activation in vivo. - Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, 2004. Host: Bruce Aronow. - Washington University School of Medicine, St. Louis, Missouri, 2004. Hosts: Mark Johnston, Sean Eddy. - Washington University Department of Computer Science, St. Louis, Missouri, 2004. Host: Michael Brent. - Indiana University School of Medicine, Indianapolis, Indiana, 2004. Host: A. Keith Dunker. ABSTRACTS PUBLISHED OR PRESENTED 2009 *Jessen WJ, Miller SJ, Hardiman A, Wu J, Giovannini M, Aronow BJ, Ratner N. Nerve gene expression patterning in NF1 mouse models. *Platform presentation at the Children's Tumor Foundation Annual NF Conference 2009, Portland, OR. 2009 Ratner N, Jessen WJ, Miller SJ, Zheng L, Hedge R, Mehta T, Hardiman A, Li H, Upadhyaya M, Giovannini M, Muir D, Wallace MR, Lopez E, Serra E, Lazaro C, Stemmer-Rachamimov A, Page G, Aronow BJ. Using Gene Expression analysis to identify NF1 clinical targets. The Children's Tumor Foundation Annual NF Conference 2009, Portland, OR. 2008 Miller SJ, Jessen WJ, Mehta T, Hardiman A, Sites E, Kaiser S, Jegga A, Li H, Upadhyaya M, Giovannini M, Muir D, Wallace MR, Lopez E, Serra E, Lazaro C, Stemmer-Rachamimov A, Page G, Aronow BJ and Ratner N. Molecular Genomic Analysis of NF1 Neurofibromas and MPNST Reveals Recapitulation of Distinct Stages of Schwann Cell Development and Identifies SOX9 as an MPNST Survival-dependent Oncogene. The Children's Tumor Foundation Annual NF Conference 2008, Bonita Springs, FL. 2008 Bodi I, Jessen W, D'Souza K, Koch S, Akhter S, Wolf R, Schwartz A and Aronow B. Cell Adhesion and Fibrosis Affect the Mechanical and Electrical Coupling Of Cardiomyocytes in Human Atrial Fibrillation. FASEB J. 22:798.11. 2007 Miller SJ, Jessen WJ, Mehta T, Hardiman A, Upadhyaya M, Muir D, Wallace M, Lopez E, Serra E, Lazaro C, Stemmer-Rachamimov AO, Giovannini M, Page GP, Aronow BJ and Ratner N. Toward a Molecular Model of Tumor Formation in Neurofibromatosis Type 1 (NF1): Global Gene Expression Comparison to Normal Human Schwann Cells Distinguishes Benign and Malignant Peripheral Nerve Sheath Tumors. The Children's Tumor Foundation Annual NF Conference 2007, Park City, UT. 2007 Hummel T, Jessen WJ, Mahler Y, Miller SJ, Kluwe L, Mautner V, Giovannini M, Stemmer-Rachamimov AO, Wallace M, Lazaro C, Page GP, Cripe T, Aronow BJ and Ratner N. Microarray gene expression data utilized to identify possible serum biomarkers of Neurofibromatosis type 1. The Children's Tumor Foundation Annual NF Conference 2007, Park City, UT. 2007 Ouyang X, Jessen WJ, Al-Ahmadie H, Serio AM, Lin Y, Shih J, Shen MM, Aronow BJ, Vickers AJ, Gerald WL and Abate-Shen C. Expression of the AP-1 transcription factor, c-Jun, is associated with recurrence of prostate cancer. The National Cancer Institute Mouse Models of Human Cancers Consortium Meeting, Boston, MA. 2007 Miller SJ, Jessen WJ, Mehta T, Hardiman A, Upadhyaya M, Muir D, Wallace M, Lopez E, Serra E, Lazaro C, Stemmer-Rachamimov AO, Giovannini M, Page GP, Aronow BJ and Ratner N. Toward a Molecular Model of Tumor Formation in Neurofibromatosis Type 1 (NF1): Global Gene Expression Comparison to Normal Human Schwann Cells Distinguishes Benign and Malignant Peripheral Nerve Sheath Tumors. American Association for Cancer Research, Oncogenomics 2007: Dissecting Cancer Through Genome Research, Phoenix, AZ. 2006 Comstock ES, Burd CJ, Karch JM, Revelo MP, Buncher CR, Jessen WJ, Aronow BJ and Knudsen KE. Impact of Cyclin D1 Localization and Molecular Profiling in Prostate Cancer. Annual Meeting of the American Association for Cancer Research, Washington, D.C. 2005 Gudivada RC, Jessen WJ, Jegga AG and Aronow BJ. Analysis of metastasis suppressor genes: comparative genomics and systems biology approaches. Intelligent Systems for Molecular Biology Conference (ISMB) 2005, Detroit, MI. 2004 Dhasarathy A, Carvin CD, Jessen WJ and Kladde MP. Promoter occupancy governs the requirement for chromatin remodeling complexes at PHO5. Student Research Poster Competition, 2004 Agriculture Program Conference, Texas A&M University. 2003 Dhasarathy A, Carvin CD, Jessen WJ and Kladde MP. Promoter occupancy governs the requirement for chromatin remodelers. Lost Pines Conference, University of Texas, M.D. Anderson Conference Center, Science Park. 2003 Carvin CD, Dhasarathy A, Friesenhahn LB, Jessen WJ and Kladde MP. Targeted cytosine methylation for in vivo detection of protein-DNA interactions. 22nd Summer Symposium in Molecular Biology: Chromatin structure and function. 2003 Dhasarathy A, Carvin CD, Jessen WJ and Kladde MP. Promoter occupancy governs the requirement for chromatin remodelers at PHO5. 2003 Federation of American Societies for Experimental Biology (FASEB) Summer Research Conference: Chromatin and Transcription. 2003 Carvin CD, Dhasarathy A, Friesenhahn LB, Jessen WJ and Kladde MP. Targeted cytosine methylation for in vivo detection of protein-DNA interactions. 2003 Federation of American Societies for Experimental Biology (FASEB) Summer Research Conference: Chromatin and Transcription. 2002 Jessen WJ, Carvin CD, Dhasarathy A, McKinnie J and Kladde MP. Single-molecule characterization of nucleosome disruption at the PHO5 promoter. Lost Pines Conference, University of Texas, M.D. Anderson Conference Center, Science Park. 2002 Carvin CD, Jessen WJ, Parr RL and Kladde MP. Target gene methylation: Using DNA methyltransferases to detect DNA-protein interactions in vivo. Lost Pines Conference, University of Texas, M.D. Anderson Conference Center, Science Park. 1997 Jessen WJ, Miller S and Najaf-Zadeh R. Dielectric breakdown and spark generation. Eighth Annual Argonne Undergraduate Research Symposium, Argonne National Lab. TEACHING AND TRAINING - Directed research projects for rotating graduate students Daniel Neef, Robert Pratt and Madhuri Jasti. Responsible for the primary training of undergraduate students Lauren Crouch, April Peterson, Holly Gregory, Rachel Kennedy and Clayton Sontheimer, 1998 - 2004. - Teaching Assistant, Texas A&M University, Experimental Biochemistry Lab, 2003. - Teaching Assistant, Texas A&M University, Biochemistry Laboratory I and II, 1998 - 1999. - Physics and Math Tutor, Purdue University Calumet, 1998. - Teaching Assistant, Purdue University Calumet, Introductory Physics, 1998. AWARDS AND HONORS - Recipient, National Institutes of Health Pediatric Research Loan Repayment Program, 2005 - 2007. - NIH NRSA Postdoctoral Fellowship, Institute of Molecular Pharmacology and Biophysics, University of Cincinnati College of Medicine, 2004 - 2007. - Participated in the development of NIH proposal "Regulation of gene expression in chromatin", funded in 2003 (Kladde MP, Texas A&M University), 2001. - Nominated to Sigma Xi, The Scientific Research Society, 1998. - "Best and Brightest" award, Department of Chemistry and Physics, Purdue University Calumet, 1998. - President, Society of Physics Students (SPS), Purdue University Calumet, 1998. PROFESSIONAL SOCIETY MEMBERSHIPS - Sigma Xi - International Society for Computational Biology - Indiana Health Industry Forum - National Eagle Scout Association REFERENCES Available upon request.