Wednesday, September 8, 2004

12:00-1:00    Conference Registration

1:00-1:10    Welcoming Remarks from Conference Director

1:10-1:25    Report from the Executive ThinkTank

CASE STUDIES OF PROTEOMIC BIOMARKER APPLICATIONS

1:25-1:30    Chairperson's Opening Remarks
Dr. Scott D. Patterson, Director, Medical Sciences, Amgen Inc.

1:30-2:00    The Role of Serum HER-2/neu as a Biomarker in the Management of Patients with Metastatic Breast Cancer
Dr. Walter Carney, President, Oncogene Science, Bayer Health Care
In this presentation I will discuss the role of the circulating HER-2/neu Oncoprotein in the management of patients with metastatic breast cancer. In particular, I will discuss longitudinal monitoring of the HER-2/neu extracellular domain in patients being treated with a variety of therapies and discuss how this diagnostic biomarker can guide therapeutic decisions.

2:00-2:30    Evaluation of a Potential Anti-Tumor Compound Using an Integrated Biomarker Approach 
Dr. Stanley M. Belkowski, Senior Scientist, Target Validation Team, Johnson and Johnson Pharmaceutical Research and Development, L.L.C. 
In an effort to determine the efficacy of an anti-tumor compound, we have used an integrated approach combining traditional and novel histopathological methods in conjunction with the development and application of several proteomic and genomic biomarkers. These data in total have determined the efficacy of the compound in both in vitro and in vivo tumor model systems as well as helped the characterization of the potential mechanism of action of the compound. Use of this integrated approach has proven to be a valuable tool in compound evaluation.

2:30-3:00    Discovery of Serum Biomarkers for Cancer Diagnostics
Dr. Daniel W. Chan, Director, Biomarker Discovery Center, Johns Hopkins University
Cancer is a proteomic disease. Studies of cancer proteomics not only allow us to better understand the biology of cancer, but also provide us the opportunities to identify protein biomarkers for cancer diagnostics. Since cancer is heterogeneous, maximum clinical usefulness is likely to require a panel of biomarkers. A case study using surface-enhanced laser desorption-ionization (SELDI) mass spectrometry for serum biomarker discovery will be presented. Antibodies for several discovered proteins have been used to develop a clinical diagnostic panel for the early detection of cancer.

3:00-3:30    Predicting Response to Biologic Therapy: Role of HMGB1
Dr. Michael T. Lotze, Director, Translational Research, Molecular Medicine Institute, University of Pittsburgh School of Medicine
HMGB1 is a highly conserved 30kD eukaryotic nuclear regulatory factor, released from necrotic cells and activated macrophages. It stimulates TNF production and inflammation, promotes sickness behavior, is an endogenous pyrogen, enhances tumor growth, promotes endothelial activation leukocyte recruitment and adhesion, and mediates death in sepsis. HMGB1 is a biologically potent co-stimulus of inflammation promoting IFN? release in the presence of IL-1, IL-2, and IL-12. It is elevated to extraordinary levels in the serum of patients with metastatic melanoma, suggesting its potential utility as an important new biomarker for patients on biologic therapy regimens.

3:30-4:30    Grand Opening of Exhibit Hall with Poster Viewing and Refreshment Break

5:00-5:30    Integrated Proteomic And Gene Expression Study Of ER-beta Agonist to Support Clinical Development
Dr. Orest Hurko, Associate Vice President, Discovery Medicine, Wyeth Research 
The identification of pharmacodynamic and disease-related biomarkers to validate animal models of disease and support clinical development of therapeutic candidates is of increasing importance to the pharmaceutical industry. ERB-041 is a small molecule nonsteroidal ER agonist that demonstrates a potent anti-inflammatory activity in two in vivo models: one of inflammatory bowel disease (HLA-B27 transgenic rat), and one of rheumatoid arthritis (Lewis rat adjuvant-induced arthritis). Using the Lewis rat model, we have recently analyzed tissue mRNA expression patterns as well as changes in the plasma proteome in response to disease induction and ERB-041 treatment to identify disease-related biomarkers of drug activity. 

5:30-6:00    Utilities of Novel Protein Biomarkers for Traumatic Brain Injury in Preclinical and Clinical Research and Drug Development
Dr. Kevin K.W. Wang, Director, Center for Neuroproteomics and Biomarkers Research; Scientific Director, Center for Traumatic Brain Injury Studies; and Associate Professor of Department of Psychiatry & Neuroscience, McKnight Brain Institute, University of Florida
Traumatic brain injury (TBI) is a major disease. Pharmaceuticals are beneficial in animal models, but there are many clinical drug trial failures. Clinical biomarkers that correlate with disease severity and progression and drug response are missing. Since existing biomarkers have marginal correlation with TBI severity, novel biomarkers are needed. Our lab shows that aII-spectrin breakdown products (SBDP's) are prototypic biomarkers for TBI. We have used proteomics to identify additional biomarkers for brain injury. Once they are identified, sensitive methods can be developed for their detection in CSF and blood. We are integrating a proteomics-based approach to discover novel biomarkers. We have data on 2D-gel electrophoresis-MALDI-TOF, 2D-liquid chromatography (LC)-MALDI-TOF and MS/MS, and antibody panels and microarrays.

6:00-6:30    Discovery of Early Plasmatic Markers for the Diagnosis of Stroke
Dr. Jean-Charles Sanchez, Biomedical Proteomics Research Group, Central Clinical Chemistry Laboratory, Geneva University Hospital
Vascular cerebral accident, or stroke, is a leading cause of death and disability in industrialized countries. Currently, a diagnosis of stroke relies on physician evaluation of the patient and neuro-imaging such as CT scan and/or MRI. An early diagnostic plasmatic marker of stroke would allow immediate therapeutic interventions and hence reduce the extent of damage and risk of death. However, the difference in the protein copy numbers in body fluids such as plasma or cerebrospinal fluid limits the discovery of novel diagnostic markers. Up to 12 orders of magnitude can be encountered when comparing the most abundant plasma protein (albumin) and a single protein copy released in the plasma by a cell. Nowadays, the current state of technologies cannot display such differences in protein concentration. The separation of these proteins in amounts sufficient for quantitative evaluation is an important issue in proteome studies and presents a real challenge for the development of new diagnostic tools. This wide dynamic range can be overcome by the use of an appropriate model that can simplify the protein complex mixture. Here, we report the use of post-mortem cerebrospinal fluid as a model of massive brain damage and its application for the discovery of early plasmatic markers for the diagnosis of stroke.

6:30-7:30    Networking Reception and Exhibit Hall