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Monday, May 19

7:00 - 6:00 pm Registration Open

7:30 Morning Coffee

8:10 Opening Plenary Introduction

8:20 Molecular Targets & Diagnostics: Critical Role of Sample Preparation in Discovery
James L. Wittliff, Ph. D., M. D. hc, FACB, Professor of Biochemistry & Molecular Biology, James Graham Brown Cancer Center, University of Louisville
Clinically relevant genomic and proteomic test development using human tissue specimens requires specialized collection, handling and cryopreservation methods for generating reliable analyses. Although global gene expression assays of intact cancer biopsies are utilized to distinguish patterns, validation of mRNA expression of specific gene sets by techniques such as quantitative PCR is essential using well characterized samples. Non-distructive procurement of pure cell populations from frozen and formalin-fixed, paraffin-embedded tissues by Laser Capture Microdissection and optimized methods for RNA and protein analyses enhance identification of candidate molecular targets for development of drugs and diagnostics. These approaches must be complemented by well annotated records of patient characteristics, tissue pathology and clinical outcome


View a Life Science webcast w/ James L Wittliff from last year's GOT Summit conference

9:00 Opportunities and Obstacles in Proteomic Analysis of Biofluids
Sunny Tam, Ph.D., Research Associate Professor, University of Massachusetts Medical School
Proteomic analyses of biofluids, such as plasma or amniotic fluid, traditionally have the same obstacles due to the presence of abundant proteins and large dynamic range of protein concentration. Recent fractionation reagents have helped in the isolation of abundant proteins to allow the examination of lower abundant proteins. We have examined plasma from a diabetic rat model and important clinical diseases after adequatefractionation schemes. The proteomic finding from gel based and iTRAQ based studies have yielded interesting observations after bioinformatics analysis. Furthermore, the biological significances of the differential protein expression have been validated with traditional biochemical methods.

9:40 Grand Opening Coffee Break in the Exhibit Hall

Data Analysis

10:25 Chairpersonís Remarks

10:30 Microarrays: Bench-to-Bedside
Towia Libermann , Ph.D., Associate Professor of Medicine, Beth Israel Deaconess Medical Center
Functional genomics and proteomics approaches have rapidly evolved over the last years and have provided the basis for groundbreaking discoveries in basic and clinical research. As the technologies become more mature and validated, bench-to-bedside clinical applications rapidly emerge. Our focus has been to identify gene signatures in patients with various types of cancer for early detection, cancer progression, metastasis, survival as well as resistance or sensitivity to therapy. We have developed novel bioinformatics approaches for biomarker discovery and individualized gene expression analysis that are enhancing the identification of aberrant signaling pathways in individual patients and clinical application of microarray data for patient stratification and management. Examples of microarray and bioinformatics approaches and their potential clinical applications in renal, prostate and breast cancer will be presented together with the implementation of the new fully automatized Affymetrix platform for high throughput 96 well microarray analysis.

11:00 Molecular Classification of Gliomas: Let the Data Inform Treatment
Jean Claude Zenklusen, Ph.D., Staff Scientist, Neuro-Oncology Branch, National Institutes of Health, National Cancer Institute
Primary brain tumors are the fourth leading cause of cancer mortality in adults under the age of 54 and the leading cause of cancer mortality in children in the United States due to suboptimal therapeutic approaches, hindered by lack of understanding of the biology of these tumors. In the framework of the Glioma Molecular Diagnostic Initiative at the NCI, we have collected and molecularly characterized (at both RNA and DNA) over 500 gliomas with corollary clinical data. Here we present a novel, comprehensive, classification of Gliomas (both high and low grade) based on their mRNA expression profiles, which were analyzed using a variety of class discovery algorithms (HC, K-mean, NMF) without using any pre-conceived notion of their biological or clinical/histopathological grouping. The results were validated in a separate datasets (either produced by our own group or from previously published reports), and classify these tumors into six distinct subclasses having a nested hierarchy correlating with the tumorís characteristics from both biological and clinical standpoints. This novel classification along with the wealth of genomic data produced by the GMDI may allow for the development of a more rational, objective, diagnostic of gliomas and serve as an important starting point in the search for new molecular therapeutic targets.

11:30 Microarray Data Analysis
Yudong He, Ph.D., Scientist, Rosetta Merck

12:00 pm Lunch and Learn Workshops
(Sponsorship Available) or Lunch on Your Own

 

Models to Predict Responses

1:25 pm Chairpersonís Remarks

1:30 Response Markers to Imatinib Mesylate in the Treatment of Gastrointestinal Stromal Tumor
Andrew Godwin, M.D., Member, Director, Clinical Molecular Genetics Laboratory; Director, Biosample Repository, Medical Oncology, Fox Chase Cancer Center
Most Gastrointestinal Stromal Tumors (GISTs) contain gain-of-function, i.e., oncogenic mutations in c-KIT or in Platelet Derived Growth Factor Receptor alpha (PDGFRa) and GIST patients are treated with imatinib mesylate, originally referred to as STI571 or GleevecTM, an oral 2-phenylaminopyrimidine derivative that acts as a selective inhibitor against oncogenic forms of KIT, PDGFa, and BCR-ABL. What is becoming apparent is that clinical management of GIST may benefit from molecular characterization, i.e., pre-selecting patients for treatment with imatinib or additional first and second line therapies based on c-KIT and PDGFRa mutational status or predictive gene signatures. As part of a recent Phase II Trial of neoadjuvant/adjuvant imatinib for advanced primary and recurrent operable GISTs (RTOG-0132), we used gene profiling of pre- and post-imatinib treated biopsies to better define prognostic markers. The analysis identified 38 genes as differentially expressed in pretreatment samples between responders and nonresponders, with all genes present at higher levels in nonresponders. Interestingly, seven of these genes mapped to a single locus on chromosome 19p and a subset of these faithfully predicted likely response to imatinib-based therapy in naive panel of GISTs.

2:00 COXEN: Genomic Prediction of Patientsí Responses to Combination Chemotherapeutics
Jae Lee, M.D., Associate Professor, Public Health Sciences, University of Virginia School of Medicine
The U.S. National Cancer Institute has used a panel of 60 diverse human cancer cell lines (the NCI-60) to screen >100,000 chemical compounds for anticancer activity. We asked whether it would be possible to identify common chemosensitivity biomarkers from that rich database to predict drug activity in cell types not included in the NCI-60 panel or, even further, clinical responses in patients with tumors. We address that challenge by developing a novel pharmacogenomic prediction approach "Co-eXpression ExtrapolatioN" (COXEN), which can effectively identify concordant genomic chemosensitivity biomarkers between two independent expression profiling data sets, here extrapolating the genomic expression patterns of NCI-60 biomarkers with those of clinical tumors. Applying our COXEN approach in a prospective fashion, we predicted anticancer drug activities on human patients in breast, ovarian, bladder cancer, and other types of cancer, who were treated with commonly used combination chemotherapeutics. We also used COXEN for in silico screening of 45,545 compounds and identify a novel agent with superior growth inhibition activity against human bladder cancer.

2:30 Use of Genomics as a Tool to Identify Stage-Appropriate Therapeutic Intervention Strategies
Marti Jett, M.D., Chief, Department of Molecular Pathology, Walter Reed Army Institute Research
Genomic patterns have the potential to reveal the progression of host responses during illness and help to pinpoint early indicators of tissue involvement or organ failure. In combination with limited proteomics, these findings can be used to identify markers that will permit therapeutic efforts to be focused to divert impending serious outcomes. Our studies using a systems approach to integrate clinical, physiological, -omics and mathematical modeling have revealed stages of illness progression during which time certain standard therapies may no longer be effective, yet they also reveal other therapeutic strategies. The aim is to identify sets of biomarkers that could be rapidly determined for near-real-time assessment of patient status.

3:00 Networking Refreshment Break, Poster and Exhibit Viewing

 

Stability and Standardization

3:45 Pathogen Surveillance and Discovery in Acute 
and Chronic Disease

W. Ian Lipkin, M.D., John Snow Professor of Epidemiology, Professor of Neurology and Pathology, Columbia University
Advances in nucleic acid technologies have revolutionized microbiology by facilitating rapid, sensitive pathogen surveillance and differential diagnosis of infectious diseases. Implementation of these technologies will enable effective intervention and reveal unappreciated links between infection and chronic diseases. I will review various assay platforms and describe a staged strategy for microbiological-diagnostics

Sponsored by

4:15 Cytogenetic Stability and Molecular Profiling of Clinical Stem Cell Products
Robert Deans, Ph.D., Senior Vice President, Regenerative Medicine, Athersys, Inc .
Production of adult stem cells for clinical use requires extensive safety testing, and demonstration that biological potency is retained over significant population doublings in expansion. We have utilized chromosomal SNP analysis to augment karyotypic stability measurements, and transcriptional profiling and gene methylation analysis to demonstrate equivalency of early and late expansion products. Use of differential profiling strategies has allowed discovery of novel marker sets which distinguish primitive from more mature adult stem cell types.

4:45 Standardisation and External Quality Controls for Gene
Expression Measurements in the Clinic: Lessons from BCR ABL Dosage in the Tyrosine Kinase Inhibitors Era
Jean Gabert, Professor, M.D., Ph.D., Biochemistry & Molecular Biology, University Hospital, Marseille

Standardisation and external quality controls are part of the routine in clinical biochemistry since years. International standards and external quality control rounds are absolutely warranted for any new biological marker for its worldwide use in the clinic. Taking the measurement of BCR ABL transcripts (M-BCR) as a model, we developed freeze dried cells that can be sent worldwide at room temperature. During, the meeting will be reported our efforts in this field at the regional,
national and international levels.

5:15 Reception in the Exhibit Hall

6:30 End of Day


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Cambridge Healthtech Institute | Beyond Genome | Bio-IT World | Biomarker World Congress | Insight Pharma Reports | Discovery On Target |
Digital Healthcare & Productivity | Bio-It World Conference & Expo | Molecular Medicine Tri-Conference | PepTalk | PharmaWeek |†
World Pharmaceutical Congress 

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