AGENDA/SPEAKERS*

8.05 – 8.30 AM: Monica Mody, PhD. Senior Application Specialist, Affymetrix, Inc. Santa Clara, CA
Title: GeneChip® Platform Applications in Clinical Research

8.30 – 9.00 AM: John Tonkinson, PhD. Marketing Manager, Schleicher & Schuell Bioscience, Inc. Keene, NH
Title: Practical Proteomics -Transitioning ELISA assays to a Quantitative Microspot Format

9.00 – 9.30 AM: Jason Goncalves, Co-founder and Chief Scientific Officer, Iobion Informatics, LLC. Toronto, Canada
Title: Turning gene expression, protein-protein, metabolic and scientific literature into knowledge with PathwayAssist

9.30 – 9.45 AM: Break

9:45 – 10.55 AM: Session I: Diagnostics & Drug Development: PharmacoGenomics Approach

9.45 – 10.00 AM: Chairman’s Welcoming Note
K. Appasani, PhD., MBA. GeneExpression Systems, Inc.
Session I: Chair

10.00 – 10.30 AM Inaugural and Keynote Lecture by
Francis Barany, PhD. Professor of Molecular Biology
Joan and Sanford I. Weill Medical College of Cornell University, New York, NY
Title: Harmonized Microarray / Mutation Scanning and Methylation Analysis of Colorectal Tumors

10.30 – 10.55 AM: Jeffrey S. Ross, M.D. Vice President of Molecular Medicine, Millennium Pharmaceuticals, Inc. Cambridge, MA, and Chairman of the Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY
Title: The Integration of PharmacoGenomics in the Development of the Proteasome Inhibitor VelcadeTM

10.55 – 11.20 AM: Refreshment Break (30 min): Sponsored by MetriGenix, Inc. Gaithersburg, MD

                         Opening of Exhibit booths and set up of Posters 

11.20 – 1.00 PM: Session II: Biomarkers-1, Surgiomics and Clinical Genomics
Session Chair: Towia A. Libermann, PhD. Associate Professor, Harvard Medical School, Boston, MA

11.20 – 11.45 AM: William Gerald, M.D., PhD. Member, Memorial Sloan-Kettering Cancer Center and Attending Pathologist at Memorial Hospital and Joan and Sanford I. Weill College of Medicine of Cornell University, New York, NY
Title: Addressing clinically relevant issues in prostate cancer using genome-wide expression analysis of human tumors

11.45 – 12.10 AM: Steven R. Gullans, PhD. Chief Scientific Officer, U.S. Genomics, Inc. Woburn, MA and Associate Professor, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA
Title: Elucidating Biomarkers: Looking for a Few Good Genes

12.10 – 12.35 AM: Towia A. Libermann, PhD. Associate Professor, Harvard Medical School and Director of Genomics Core Facility at Beth Israel Deaconess Medical Center, Boston, MA
Title: Functional genomics and proteomics approaches to human disease

12.35 – 1.00 PM: Eric M. Eastman, Ph.D. Chief Scientific Officer, MetriGenix, Inc. Gaithersburg, MD
Title: MGX 4D ArrayTM Platform: Integrating Genomics and Bioinformatics for Cancer Research and Drug Discovery

       1.00 - 2.15 PM: Lunch break (1.15 Min) Lunch provided by GeneExpression Systems, Inc.

                                  Visiting Exhibits and Posters   

2.15 – 3.30 PM: Session III: New Technology and ToxicoGenomics
Session Chair: Jingyue Ju, PhD. Associate Professor, Columbia Genome Center, New York, NY

2.15 – 2.40 PM: Thomas J. Vasicek, PhD. Vice President of Business Development, Lynx Therapeutics, Inc. Hayward, California
Title: Defining the transcriptome with Massively Parallel Signature Sequencing

2.40 – 3.05 PM: Jingyue Ju, PhD. Associate Professor and Head of DNA Sequencing and Chemical Biology, Columbia Genome Center and the Department of Chemical Engineering, Columbia University College of Physicians & Surgeons, New York, NY
Title: Chemical and Molecular Engineering Approaches for New Paradigm in DNA Sequencing and Analysis

3.05 – 3.35 PM: Jeffrey Waring, PhD. Associate Research Investigator, Abbott Laboratories, Abbott Park, IL
Title: Developing a Gene Expression Database for Predicting Toxic Responses in Drug Discovery

3. 35 – 4.15 PM:
Break (40 min) Poster and Exhibits viewing-Judging for Best Poster Awards

4.15 – 5.30 PM: Session IV: Industrial Omics
Session Chair: J. L. Walewski, PhD. Assistant Professor, Mt. Sinai School of Medicine, New York, NY

4.15 – 4.40 PM: John D. Burczak, Ph.D. Vice President, Research & Development, Amersham Biosciences, Piscataway, NJ
Title: CodeLink Three Dimensional Bioarrays for Gene Expression and SNP Analysis

4.40 – 5.05 PM: Jose L. Walewski, PhD. Assistant Professor, Mount Sinai School of Medicine and Director of Microarray Core Facility at Mount Sinai Hospital, New York, NY
Title: Microarray Analysis of Model Systems of Lliver Disease

5.05 – 5.30 PM: Paul Predki, PhD. Vice President, Research & Development, Protometrix, Inc. Branford, CT
Title: Improving the Drug R&D Process with Functional Proteome Microarrays
                            
                                5.30 PM: End of Day I Sessions

                               Day 2: Thursday, October 2:

8:00 – 10:00 AM: Continental breakfast:

8.25 - 8.30 AM: Chairman’s Opening remarks

8.30 – 9.45 AM: Session V: High Throughput Genomic Methodologies
Session Chair: Chris Boles, Ph.D. Vice President & Chief Scientific Officer, MatrixTechnologies Corp. Hudson, NH

8.30 – 8.55 AM: Ralph R. Martel, PhD. Vice President, High Throughput Genomics, Inc, Tucson, AZ
Title: ArrayPlate Technology to Enable Genomics-Driven Drug Discovery and Diagnostics

8.55 – 9.20 AM: Chris Boles, Ph.D. Vice President & Chief Scientific Officer, Matrix Technologies Corp.
Hudson, NH
Title: Microarrays in Microplates for High-Throughput Genomic Analyses

9.20 – 9.45 AM: Anis H. Khimani, Ph.D. Director of Marketing, MDS, Ventana Medical Systems, Inc. Tucson, AZ
Title: A Systems Approach to Higher Throughput and Optimization in Microarrays, IHC, and ISH applications

9.45 – 10.00 AM: Break

10.00 – 10.10 AM: Awards Announcement and Presentation

10.10 – 11.30 AM: Session VI: Biomarkers 2, Clinical Proteomics
Session Chair: Sam Hanash, MD., PhD. Professor of Pediatrics, University of Michigan, Ann Arbor, MI

10.10 – 10.40 AM: Keynote Lecture by
Sam Hanash, MD., PhD. Professor of Pediatrics, University of Michigan, Ann Arbor, MI and President, Human Proteome Organization (HUPO)

10.40 – 11.05 AM: Thomas P. Conrads, Ph.D. Associate Director, Laboratory of Proteomics, National Cancer Institute, SAIC, Frederick, MD
Title: Application of High-resolution Mass Spectrometry for Ovarian Cancer Detection

11.05 - 11.30 PM: Refreshment Break (25 min) Poster and Exhibits viewing

11.30 – 12.45 AM: Session VII: Transcription profiling & OncoGenomics
Session Chair: David Munroe, PhD. Director, Laboratory of Molecular Technology, National Cancer Institute, FCRF, Frederick, MD

11.30- 11.55 AM: Stephen D. Nimer, MD. Head, Division of Hematological Oncology, Memorial Sloan-Kettering Cancer Center, and Professor of Medicine, Weill College of Medicine of Cornell University, New York, NY
Title: Unraveling Acute Leukemias by Transcript Profiling

11.55 – 12.20 PM: David Munroe, PhD. Director, Laboratory of Molecular Technology and Vice President of Program Management, National Cancer Institute, FCRF, Frederick, MD
Title: The use of DNA and protein microarrays for the identification of diagnostic and prognostic markers in cancer

12.20 – 12.45 PM: Robert Dullea, PhD. Cancer Profiling Group, Pfizer R&D, Groton, CT
Title: The Application of Oligonucleotide Array Technology to Identify Novel Targets for the Treatment of Cancer

                       12.45 – 2.00 PM: Lunch Break (1 hr. 15 min) on your own

2.00 – 3.45 PM: Session VIII : NeuroGenomics, Proteomics and BioInformatics
Session Chair: Michael Mallamaci, Ph.D. Principal Scientist, AstraZeneca Pharmaceuticals, Wilmington, DE

2.00- 2.25 PM: Ghil Jona, PhD. (Dr. Michael Snyder’s Lab), Yale University, New Haven, CT
Title: Global analysis of biochemical activities using protein microarrays

2.25 – 2.50 PM: Michael Mallamaci, Ph.D. Principal Scientist, AstraZeneca Pharmaceuticals, Wilmington, DE
Title: Applying Microarrays in CNS Discovery: focus on Micro-dissection

2.50 - 3.15 PM: Jeffrey Brockman, PhD. Senior Scientist, Psychiatric Genomics, Inc. Gaithersburg, MD
Title: Using Laser Capture Micro dissection and Multiple Gene Expression Profiling Technologies to Identify Gene Signatures of Psychiatric Disease

3.15 - 3.45 PM: Javier Cabrera, PhD. Rutgers University, Piscataway and Johnson & Johnson PRD LLC. Raritan, NJ
Title: Microarray data mining in JNJ drug discovery

3.45 – 4.15 PM: Refreshment Break (30 min) Poster and Exhibits viewing

4.15 PM: Removal of Posters and Exhibit booths

4.15 – 5.30 PM: Session IX. PANEL DISCUSSION: Technology transfer, Intellectual Property, and Investment opportunities
Session Moderator: K. Appasani, PhD., MBA. GeneExpression Systems, Inc.

4.15 – 4.25 PM: Introduction of Panel Members by Chairman

4.25 – 5.25 PM: Panel Discussion with experts from:

Venture Capital firm:
Joseph F. Lawler, MD., PhD. Principal, J.P. Morgan Partners, New York, NY

Patent Law Firm:
Kenneth H. Sonnenfeld, PhD., JD. Partner, Morgan & Finnegan Intellectual Property Law Firm, New York, NY

Duncan A. Greenhalgh, PhD. Associate, Patent and Intellectual Property, Testa, Hurwitz & Thibeault, Boston, MA

University Technology Transfer Officer
Niva Almaula, PhD. Technology Licensing Manager, Rockefeller University, New York, NY

Selected Academic Speaker from the meeting
Sam Hanash, MD., PhD. Professor of Pediatrics, University of Michigan, Ann Arbor, MI, and President, Human Proteome Organization

Selected Industry Executive from the meeting
Charles T. Tackney, Science Director, Ortho-Clinical Diagnostics, Inc. Raritan, NJ (Not confirmed)

Professional Journalist (Not finalized)
           
                                 5.25 – 5.30 PM: CLOSING REMARKS BY THE CHAIRMAN

*The actual agenda in the meeting may be changed.

• K. Appasani, PhD., MBA. GeneExpression Systems, Inc.
  
• T. A. Libermann, PhD. Associate Professor, Harvard Medical School
  
• C. Boles, PhD. CSO, Matrix Technologies
  
• J. L. Walewski, PhD. Assistant Professor, Mount Sinai School of Medicine
  

Speakers Abstracts:

Harmonized Microarray / Mutation Scanning and Methylation Analysis of Colorectal Tumors
Renya Favis, Yu-Wei Cheng, Jianmin Huang, Norman P. Gerry, Philip Paty, Thierry Soussi and Francis Barany, Department of Microbiology, Hearst Microbiology Research Center and Strang Cancer Prevention Center, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Ave., Box 62, New York, NY 10021, USA

Molecular profiling of solid tumors is confounded by infiltrating wild-type cells, since normal DNA can interfere with detection of mutant sequences. Our objective was to identify p53 mutations in 138 stage I-IV colorectal adenocarcinomas and liver metastases without first enriching for tumor cells by microdissection. To achieve this, we developed a harmonized protocol involving multiplex polymerase chain reaction/ligase detection reaction (PCR/LDR) with Universal DNA microarray analysis and EndonucleaseV/ligase mutation scanning. Sequences were verified using dideoxy sequencing. The harmonized protocol detected 66/66 (100%) of mutations. Dideoxy sequencing detected 41/66 mutations (62%) using automated reading, 59/66 mutations (89%) with manual reading. Data analysis comparing colon cancer entries in the p53 database (http://p53.curie.fr) with the results reported in this study showed that distribution of mutations and the mutational events were comparable. We have now extended this technology to include bisulfite treatment for multiplexed detection of methylation status in tumor samples using our Universal Array readout assay.

The Integration of PharmacoGenomics in the Development of the Proteasome Inhibitor Velcade™
Jeffrey S. Ross, M.D. Vice President of Molecular Medicine, Millennium Pharmaceuticals, Inc. and Chairman of the Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY

The proteasome inhibitor, VELCADETM (bortezomib, PS-341) has recently been approved by the FDA for the treatment of relapsed and refractor multiple myeloma. The clinical development of this novel agent has featured a clinical pharmacogenomics strategy designed to discover the mechanisms of response and resistance to the drug. Using transcriptional profiling with oligonucleotide microarrays on bone marrow aspirated from relapsed Myeloma patients treated with VELCADETM, a series of genes and biologic pathways associated with clinical response, disease stabilization and progressive disease have been discovered. How this information is being used to enable a personalized medicine strategy for the testing of VELCADETM in both non-Hodgkin’s lymphoma and a variety of solid tumors will also be presented.

Improving the Drug R&D Process with Functional Proteome Microarrays
Paul F. Predki, Ph.D. Vice President, Research & Development, Protometrix, Inc., Branford, CT

The ability to use protein microarrays to analyze protein function and interactions with a wide variety of proteins, lipids, DNA, substrates, antibodies & small molecules on a proteome scale has only recently been realized. PROTOMETRIX has industrialized and validated the complete process required for the development of protein microarrays for these applications. A yeast proteome array (the yeast ProtoArrayTM) has already been completed, and a variety of human sub-proteome arrays are under development. Applications of these arrays, ranging from pathway characterization to drug target identification and definition of drug selectivity and specificity, will be discussed. These types of applications will improve the innovation, precision and speed of pharmaceutical drug discovery and development by impacting multiple steps in the drug research and development continuum.

Developing a Gene Expression Database for Predicting Toxic Responses in Drug Discovery
Jeffrey Waring, Ph.D. Associate Research Investigator, Abbott Laboratories, Abbott Park, IL

Drug-induced liver toxicity remains the first cause of drug-induced death and the principle reason for withdrawal of drugs from the market. Despite improved toxicology testing, the frequency of drug-induced hepatotoxicity has not decreased; in fact, over 1000 drugs have been associated with hepatic injury. Clearly, a need exists for an assay that can more accurately predict the potential for drugs to induce hepatotoxicity. We have developed a 25,000 probe microarray for profiling hepatotoxins in rat liver, and have used this array to build a compendium of hepatotoxin expression profiles. A total of 62 reference compounds have been assayed, including pharmaceutical drugs and classic inducers, as well as 9 compounds that have no known hepatotoxicity associated with them. Our results show a clear distinction between the expression profiles from hepatotoxic and non-hepatotoxic compounds. The application of this compendium of hepatotoxin liver signatures toward predictive molecular toxicology will be presented.

Using Laser Capture Microdissection and Multiple Gene Expression Profiling Technologies to Identify Gene Signatures of Psychiatric Disease
Jeff Brockman Ph.D. Senior Scientist, Microarray Group Leader, Psychiatric Genomics, Inc. Gaithersburg, MD

Over the past two years Psychiatric Genomics, Inc. has made extensive comparisons between the Affymetrix GeneChip, the Agilent cDNA array, and Q-PCR platforms. These comparisons have allowed us to model a number of data sets to determine false positive\negative rates for each of the platforms, the effect of biological variability on these rates, the number of biological samples to achieve statistical significance, and the importance of experimental design. Laser capture microdissection coupled with microarray analysis has greatly enhanced our ability to detect disease-related gene changes in postmortem brain tissues, and has yielded breakthroughs in our understanding of the etiology of schizophrenia and bipolar disease.

Applying Microarrays in CNS Discovery: focus on Microdissection
Michael Mallamaci, PhD. AstraZeneca Pharmaceuticals, Wilmington, DE

Transcript profiling experiments aimed at unraveling pathways involved in CNS disorders are confounded by the fact that cells with very different patterns of gene expression often lie within close proximity. In order to obtain data that truly reflects gene expression among the target population, samples that are comprised exclusively of the cells of interest must be obtained. The advent of laser capture micro dissection has made such discrete sampling possible. A review of our capabilities in this area will be presented; highlighting how increased Affymetrix Gene Chip system sensitivity was achieved through reduced sample heterogeneity and protocol modifications.

Global analysis of biochemical activities using protein microarrays.
Ghil Jona, PhD. Heng Zhu, Metin Bilgin, Jason Ptacek, David Hall, Geeta Devgan, and Michael Snyder, Yale University, New Haven, CT

A major challenge with the sequencing of a wide variety of organisms is to understand the function, regulation and modification of the many encoded gene products. We have been carrying out proteomics approaches to the identification and analysis of signaling pathways in budding yeast. 121 of 122 protein kinases were cloned and purified from yeast as GST fusions and analyzed for their ability to phosphorylate 60 different yeast substrates. Similarly, we have cloned and overexpressed 5800 open reading frames from yeast. The proteins were printed onto slides at high density to form a yeast proteome microarray and screened for their ability to interact with a variety of different proteins, nucleic acids and phospholipids. As examples, we have probed yeast proteome chips with calmodulin, 14-3-3 proteins and phospholipids, which revealed many new interacting proteins, as well as a potential binding motif for many of the calmodulin-binding proteins. Thus, proteome microarrays can be used to screen for diverse biochemical activities, and to screen for targets of molecules and novel drugs.

Functional genomics and proteomics approaches to human disease
Towia A. Libermann, Ph.D. Associate Professor and Director of BIDMC Genomics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA

Genomic and proteomic technologies have the promise to rapidly generate multiple disease hypotheses due to the parallel query of hundreds of thousands of data points and to drastically cut the time and costs involved in target validation. We will outline our systematic and comprehensive functional genomics strategies for transcriptional profiling, high throughput genotyping, proteomics and drug screening to define disease mechanisms at a molecular level and to identify novel prognostic and predictive markers as well as new drug targets in human disease. We will present several practical examples for streamlining and accelerating the process of disease hypothesis generation, outcome prediction and drug target validation.

GeneChip® Platform Applications in Clinical Research
Monica Mody, PhD. Raji Pillai, Shawn Becker and Gianfrance deFeo, Affymetrix, Inc. Sanata Clara, CA

The Affymetrix GeneChip platform is used to discover and validate genomic patterns that can serve as biomarkers to distinguish unique disease states and predict response to therapy. The GeneChip platform offers a broad portfolio of DNA and RNA microarray products that are currently used for clinical research in a number of disease areas, including oncology, infectious disease, immunology, cardiovascular and metabolic diseases. In this presentation, specific examples of the application of GeneChip technology to identify diagnostic signatures for disease, to elucidate treatment-specific changes in gene expression and serve as predictors of patient response to therapy will be discussed.

Protein microarrays for cancer diagnosis and monitoring
Sam Hanash, MD. PhD., Professor of Pediatrics, University of Michigan, Ann Arbor, MI

In the post-genome era several major platforms have become available for the molecular analysis of tumor tissue and biological fluids which we are applying to cancer. Genomic approaches to cancer have provided important but limited views of the range of molecular alterations that occur in lung cancer, but have not effectively translated into biomarkers for early cancer detection nor, with some exceptions, into novel targets for therapy. Proteomics provides several avenues for tumor profiling and cancer marker identification. Proteomic strategies we have implemented include analysis of differential protein expression between normal, pre-malignant and malignant tissue, analysis of the secretome of cancer cells and direct serum protein profiling to identify cancer makers. A promising proteomic approach is microarray-based serum profiling to identify patterns of serum proteins predictive of cancer and to identify tumor antigenic targets that induce an antibody response in cancer. Progress to date on the application of protein microarrays for cancer diagnosis and monitoring will be presented.

Application of High-resolution Mass Spectrometry for Ovarian Cancer Detection
Thomas P. Conrads, PhD. Associate Director, Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD

Serum proteomic pattern diagnostics is an emerging clinical paradigm that typically utilizes low-resolution mass spectrometry and generates a single set of biomarker classifiers. In the present study we utilized a well-controlled serum study set from women being followed and evaluated for the presence of ovarian cancer to extend serum proteomic pattern analysis to a higher resolution instrument platform to explore the existence of multiple distinct and highly accurate diagnostic sets of features present in the same mass spectrum. Using high-resolution mass spectral data, at least 56 different patterns were discovered that achieve greater than 85% sensitivity and specificity in testing and validation. Four of those feature sets exhibited 100% sensitivity and specificity in blinded validation tests. No models generated from data acquired from the same samples analyzed with a more common low-resolution mass spectrometer were validated as 100% sensitive and specific. The sensitivity and specificity of diagnostic models generated from high-resolution mass spectral data were dramatically superior to those generated from low-resolution mass spectral data.
Supported under NCI contract number NO1-CO-12400

CodeLink Three Dimensional Bioarrays for Gene Expression and SNP Analysis
John D. Burczak, Ph.D. Vice President, Research & Development, Amersham Biosciences, Piscataway, NJ

CodeLink is an oligonucleotide bioarray platform which utilizes a three dimensional surface. For gene expression analysis, 30mer oligonucleotide are used on the bioarray, the limited oligonucleotide length imparts high specificity. The three dimensional surface promotes hybridization kinetics similar to those in solution, and thus imparts high sensitivity. For analysis of gene expression, mRNA sequences are amplified and turned into compliment RNA (cRNA). cRNA hybridization to the expression bioarray is detected by the presence of incorporated labeled ribonucleotides. For SNP analysis, allele extension is done using oligonucleotides attached to the bioarray.

Turning gene expression, protein-protein, metabolic and scientific literature into knowledge with PathwayAssist.
Jason Goncalves, Co-founder and Chief Scientific Officer, Iobion Informatics, Toronto, Canada

Technology Workshop
Integrating multiple sources of information is the single most important step on the path to knowledge and understanding of biological processes. The seminar will review methods to integrate diverse information sources, such as gene expression data, protein-protein interaction databases and metabolic pathway databases. We will also discuss how natural language processing (NLP) techniques can be used to extract information from the richest public data source available: the body of biomedical literature. Tools for NLP and data integration will be presented through specific use cases.

Unraveling Acute Leukemias by Transcript Profiling
Stephen D. Nimer, MD. Head, Division of Hematological Oncology, Memorial Sloan-Kettering Cancer Center, and Professor of Medicine, Weill College of Medicine, Cornell University, New York, NY

Human acute leukemias are characterized by the continued proliferation of hematopoietic stem cells that can no longer differentiate into mature functional cells. These immature leukemic cells (myeloblasts or lymphoblasts) accumulate and exclude the normal functioning marrow cells. To define the fundamental basis for acute leukemia we have been characterizing target genes of transcriptional regulatory proteins that are critical for normal hematopoiesis. We have also used micro-array platforms to profile the expression patterns of normal human hematopoietic cells following the introduction of leukemia-associated oncogenes. The advantages of using human systems plus the ability to compare transcript profiles for different types of oncogenic events will aid in the unraveling of the pathogenesis of acute leukemia and the in identification of targets for directed therapies.

A Systems Approach to Higher Throughput and Optimization in Microarrays, IHC, and ISH applications
Anis H. Khimani, Ph.D. Director of Marketing, MDS, Ventana Medical Systems, Inc. Tucson, AZ

Manual methods for multiple slide processing in applications such as microarray hybridizations immunohistochemistry (IHC), and in situ hybridizations (ISH) suffer from inherent experimental variability, non-standardized protocols, and labor and time constraints. Assay optimization, enhanced productivity, consistency and reliability are critical and sought attributes of a result-oriented experimental environment. Ventana’s Discovery® system delivers the walk-away automation with novel, patented technological features such as individual temperature-controlled thermopads, liquid cover slip, air vortex mixing, and built-in quality control features. In addition to the hardware, the system is integrated for software and optimized reagents, and still allows the option and flexibility in designing 20 individual experiments for assay development purposes in multiple applications (Microarrays, IHC, and ISH). Data from the use of the 3 applications on numerous model systems from internal validations and those from collaborations will be presented.

Addressing clinically relevant issues in prostate cancer using genome-wide expression analysis of human tumors
William L. Gerald, MD., PhD. Member, Memorial Sloan Kettering Cancer Center, Attending Pathologist at Memorial Hospital and Joan and Sanford I. Weill College of Medicine of Cornell University, New York, NY

Prostate cancer is a poorly understood disease with many clinical controversies. For example: 1) Androgens play a primary role in development and progression of prostate cancer however the androgen responsive biochemical pathways that drive prostate cancer are unknown. 2) A critical challenge in early stage disease is to develop means to distinguish indolent cancers from those that are potentially lethal so that therapeutic procedures can be tailored to an individual patient. 3) Androgen ablation is a mainstay in therapy for high stage prostate cancer but response is variable and virtually all patients develop androgen ablation resistance. The mechanisms of resistance are unknown. We have used high-throughput, gene expression analysis of human tissues to develop prognostic algorithms, characterize the androgen response pathway, and define molecular profiles of androgen-independent disease.

Practical Proteomics – Transitioning ELISA Assays to a Quantitative Microspot Format
John L. Tonkinson, PhD. Marketing Manager, Schleicher & Schuell BioScience, Keene, NH

Technology Workshop
Protein microarrays may take many different forms, including complex proteome arrays, reverse lysate arrays and microscale immunoassays. At Schleicher & Schuell BioScience, our efforts are focused on transferring traditional immunoassays to a microspot format on the FASTTM slide surface. This technology workshop will focus on immunoassay parameters that are critical for potential diagnostic uses; these include dose-response slope, minimum detectable dose, reproducibility and dilutional recovery. Particular focus will be on quantitative analysis of antigens by a microspot assay.

Chemical and Molecular Engineering Approaches for New Paradigm in DNA Sequencing and Analysis
Jingyue Ju, PhD. Associate Professor and Head of DNA Sequencing and Chemical Biology, Columbia Genome Center and the Department of Chemical Engineering, Columbia University College of Physicians & Surgeons, New York, NY

DNA sequencing by synthesis on a solid surface during polymerase reaction offers a new paradigm in DNA sequencing. We report the design of such a novel DNA sequencing system using chemical and molecular engineering approaches. The design rationale of the system is to use 4 distinct fluorescent emissions or 4 mass tags to code for the identity of the 4 nucleotides (A, C, G, T) in DNA. We synthesized photocleavable fluorescent and mass-tagged nucleoside triphosphates by attaching the fluorophores and mass tags to the 5-position of 2'-deoxyribouridine triphosphate via a photocleavable 2-nitrobenzyl linker. These nucleotide analogues are faithfully incorporated by a DNA polymerase into the growing DNA strand in a polymerase reaction and their incorporation does not hinder the addition of the subsequent nucleotide. After detection to decode the sequence of the added nucleotide, UV (340 nm) irradiation of the DNA molecule leads to the efficient release of the fluorophore or mass tag, ensuring that a previous fluorescence or mass tag signal does not leave any residue that interferes with the detection of the next nucleotide. Our results indicate that it should be feasible to use four fluorophores or mass tags to label the four nucleotides through the 2-nitrobenzyl linker for DNA sequencing by synthesis on a chip or a microchannel system. Such a system has potential to perform massive parallel DNA sequencing and digital gene expression analysis for the coming era of personalized medicine.

The Application of Oligonucleotide Array Technology to Identify Novel Targets for the Treatment of Cancer
Robert Dullea, PhD. Cancer Profiling Group, Pfizer R&D, Groton, CT

The advent and continued advances in RNA expression profiling technologies have offered pharmaceutical industry researchers a tool to impact all areas of the drug development process including; target identification, compound mechanism of action, confidence in rational, and drug safety evaluation. Due largely to the availability of primary disease samples, studies of the transcriptome have advanced our understanding of the mechanisms underlying the development and progression of cancer as well as insights into treatment strategies. Recent experiments in our group utilizing a custom oligonucleotide array along with mining of expression data available in the public domain has generated a repository of genes differentially regulated in cancer tissue. Applying multiple bioinformatic approaches and partnership with therapeutic area scientists has identified novel molecular targets for the treatment of metastatic disease currently advancing through the exploratory development pipeline.

Microarrays in Microplates for High-Throughput Genomic Analyses
Chris Boles1*, Brian Patterson1, Slawek Mielewczyk1, Ezra Abrams1, Mary Tyler1, Ben Stone1, Jose Melo1, David Warwick2, Colin Reynolds2 1Matrix Technologies Corp., 22 Friars Drive, Hudson, MA, USA 03051, 800-345-0206. 2BioRobotics Ltd., The Woodlands, Barton Road, Haslingfield, Cambridge CB3 7LW, UK, +44 1223 873 500.

An integrated system for fabrication of microarrays in 96-well microplates will be presented. The consumables for the system are Matrix ez-rays™ glass-bottom 96-well plates. The glass is coated with a proprietary polyacrylamide-based polymer layer that can bind oligos, PCR products, or antibodies depending on the spotting buffer used. Plate printing software and microplate adapters have been developed for the BioRobotics MicroGrid spotter that will allow as many as 600 spots to be printed in each well. Advantages and features of the microplate format for microarray applications including analysis of gene expression, SNP typing, and multianalyte antigen detection, will be discussed.

Qualitative approaches on microarray data analysis
James J. Li, Qinghong J. Li, Javier Cabrera*, Dhammika Amaratunga#, Xiwei D. Wang, Dept. Bioinformatics, #Dept. of Non-clinical Statistics, Johnson & Johnson Pharmaceutical Research & Development, LLC and *Dept. of Statistics, Rutgers University

In many industrial settings a small number of bioinformaticians and biostatisticians face the daunting task of analyzing the deluge of data from microarray and proteomics experiments. In order to cope with the large number of analysis requests, we developed a web-based user-friendly interface that automates most of the frequently recurring analyses. A key aspect of the system is that it works in combination with a centralized data management system. In addition, there is also integration with other bioinformatics data sources/tools, such as gene annotation and pathway information. The web interface is also designed to be flexible and accommodates a wide range of analyses by providing automated decision procedures that makes it easy for scientists to perform their own data analyses. Each of the data analysis procedures included in the web interface was subject to a qualitative analysis that produced a flow graph showing all the possibilities of the process. The resulting flow graph is then implemented in the web interface. Cases of data analysis in drug discovery research and/or clinical trials, using various statistical procedures implemented in the web, such as factorial analysis, will be presented.

The use of DNA and protein microarrays for the identificationof diagnostic and prognostic markers in cancer.
Lisa Gangi, Ulises Urzua, Shirley Tsang, Lynn Rasmussen, Garrison Owens, Lionel Best, Claudia Stewart, Casey Frankenberger and David J. Munroe. Laboratory of Molecular Technology, SAIC-Frederick, National Cancer Institute at Frederick, 915 Tollhouse Road, Suite 211, Frederick, MD, 21701, USA.

The development of microarray technologies together with the recent release of the complete human and rodent genomic sequence databases and an ever increasing sophistication in bioinformatics, data analysis, and information management have driven the development of a new era in genomics and patient management. In this regard we will discuss: 1) The development of novel microarray applications; 2) The development of novel microarray platforms; 3) The integration of these microarray applications/platforms within the context of a more molecular approach to pathology and patient management; 4) Experimental design approaches; 5) Data analysis; and 6) Information management.
Finally, we will discuss direct application of these new microarray applications/strategies in the development of molecular pathology tools and reagents.

Elucidating Biomarkers: Looking for a Few Good Genes
Steven R. Gullans, Ph.D. CSO, US Genomics, Woburn, MA 01801 and Associate Professor, Harvard Medical School and Brigham & Women’s Hospital, Boston, MA 02115

Microarrays and bioinformatics provide new opportunities for uncovering molecular markers for disease diagnosis and prognosis. Most studies using arrays have defined complex signatures that allow distinction of disease subclasses. Our approach has been to identify small numbers of genes (< 10) whose expression levels, when accurately quantified, provide diagnostic and prognostic information. A study of lung cancer allowed us to distinguish malignant pleural mesothelioma from adenocarcinoma using an expression ratio-based strategy with as few as 3-5 transcripts. In addition, valuable prognostic information could be gleaned from as few as four genes. Thus, accurate quantitation of mRNA biomarkers using an expression ratio-based technique can provide a simple inexpensive approach to molecular diagnosis and prognosis

IF YOU ARE INTERESTED IN SPEAKING OR EXHIBITING IN THIS MEETING PLEASE CONTACT 781-891-8181, or email genexpsys@expressgenes.com

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