8:40 Tackling
the Challenges of Proteomics
Henry Rodriguez, Ph.D., MBA, Director, Clinical Proteomic Technologies for
Cancer, Office of Technology and Industrial Relations,Office of the Director, National Cancer Institute
Proteomics have revolutionized cell biology and biochemistry by providing
powerful new tools to characterize complex proteomes, multiprotein complexes
and posttranslational modifications. Although proteomics technologies could
address important problems in clinical and translational cancer research,
attempts to use proteomics approaches to discover cancer biomarkers in
biofluids and tissues have been largely unsuccessful and have engendered
considerable skepticism. The National Cancer Institute has taken a leading
role in facilitating the translation of proteomics from research to clinical
application, through its Clinical Proteomic Technologies for Cancer initiative
(CPTC) (http://proteomics.cancer.gov).
The goal of the CPTC is to accelerate discovery and clinical research in
cancer using an integrated approach that assesses and optimizes proteomic
technology measurement capabilities and develops universally accepted metrics
that identify and minimize experimental variability from run to run,
instrument to instrument, and lab to lab. This program will enable the
transition of proteomics technologies from basic research tools to reliable
and robust clinical research platforms.
9:20 Pharmacogenetic Testing in the Clinical Practice
10:00 Coffee Break, Exhibit and Poster Viewing
10:45 Emerging Mass Spectrometry Based Technologies in Clinical
Proteomics for Diagnostics
Christoph Borchers, Ph.D., Associate Professor, Director, Biochemistry &
Microbiology, UVic - GBC Proteomics Centre, University of Victoria
11:15 Determining Direct Compound-Target(s) Interactions in Blood
Ulrich
Kruse, Ph.D., Associate Director, Translational Research & Intellectual
Property , Cellzome
We have developed a novel technology, KinobeadsTM,
which allows us to monitor directly the interaction of a drug with its kinase
targets in the appropriate tissue. We have profiled several known and novel
kinase inhibitors in human leukocytes from healthy volunteers as well as in
white blood cells from CLL patients. The technology can also more broadly be
used to analyze the kinome in healthy and disease tissue and identify changes in
both expression levels and activation state of the kinases.The technology has
potential applications in translational studies and personalized medicine where
a drug can be interrogated for its interaction with its kinase targets in each
individual patient.
11:45 Solution Showcase
(Sponsorship
Available)
12:15 pm Luncheon in Exhibit Hall
Sponsored by
12:15 pm Luncheon in Exhibit Hall, sponsored by
1:30 Probing Cardiovascular Signaling Networks in Disease
Thomas Vondriska, M.D., Assistant Professor, Anesthesiology, UCLA I will lecture on the implementation of proteomics to reveal
topology and function of signaling networks in the heart and other cell types. I
will discuss how changes in these networks are measured during disease and are
facilitating development of novel diagnostic screening tools.
2
:00 Discovery
of Protein Biomarkers in Plasma and Tissue Joanna Hunter, Ph.D., Director, Protein Analysis, Caprion Proteomics
We are applying global proteomic profiling of circulating blood proteins in
clinical and pre-clinical studies to identify markers of disease, as well as
predictive and pharmacodynamic markers of drug efficacy and safety. A second
approach to identify low abundance, tissue specific protein biomarkers is to
interrogate proteins contained in the lumen of the Golgi in the tissue of
origin. These proteins are destined to be released into the blood, and provide
a source of easily detectable protein biomarkers.
2:30 Refreshment Break
Prognostic Biomarker and Platforms
3:00 Clinical Proteomic Analysis of Diabetes: Biomarker Discovery for End
Organ Complications
Mark Chance, M.D., Director, Center for Proteomics, Case Western Reserve
University Diabetes mellitus is estimated to affect approximately 20
million people in the US and more than 150 million people worldwide. There are
numerous end organ complications of diabetes the onset of which can be delayed
by early diagnosis and treatment. Recently, studies have been conducted to
develop accurate urine based diagnostic testing as conventional assays for
diabetes and its complications lack specificity, sensitivity and accuracy.
Utilizing label free expression analysis and 2D DIGE platforms we have
extensively investigated the protein changes in a both a diabetic rat model and
clinical urine samples to better understand the pathophysiological changes that
occur in bladder and kidney as a result of diabetes mellitus.
3:30 Biomarkers to Diagnostics - A Standardized and Quantitative
Immunohistochemistry Platform
Mark Gustavson, Ph.D., Senior Research Scientist, Diagnostics, HistoRx, Inc. There is critical need for standardized and quantitative
immunohistochemical (IHC) assays in the clinic to allow for more objective and
precise determination of established biomarker expression, and thus better
prediction of patient outcome either in terms of prognosis or response to
treatment. AQUA® analysis has been developed to specifically address this need
by providing a standardized platform that produces a precise and reproducible
quantitative expression score (an AQUA® score) through standard IHC staining
methodologies on tissue sections. Instrument and software standardization
controls (i.e. light source and imaging threshold automation) allow for
quantitative expression data to be generated between multiple instruments and
operators with %CVs of less than 5%. Standardized quantitative data for protein
expression also empowers statistical approaches to analyzing data that are
simply not possible to apply to standard IHC results, thus identification of
previously unrecognized patterns, associations and correlations for in situ
expression data are possible. Furthermore, because AQUA® analysis enables
quantification of protein expression in specific cellular and sub-cellular
compartments, quantitative relationships of biomarker expression in different
sub-cellular compartments (i.e. membrane v. cytoplasm) can be determined.
4:00 Quantitative Proteomics for Discovery of Diagnostic and Prognostic
Biomarkers Towia Libermann, M.D., Associate Professor of Medicine, Beth Israel Deaconess
Medical Center Proteomics technologies are rapidly evolving over the last
years and are providing the tools for biomarker discovery in human diseases.
While mass spectrometry until recently had major limitations with regard to
quantitation, sensitivity and throughput when applied to larger sets of clinical
samples, recent technological developments have resulted in significant
enhancements that make clinical proteomics feasible. Our focus is to identify new
diagnostic and prognostic biomarkers in bodily fluids of patients with various
types of diseases. We are applying the latest technologies for protein
depletion, multi-dimensional peptide fractionation, and isobaric protein
labeling for multiplexing of up to eight patient samples in conjunction with
tandem mass spectrometry on the Applied Biosystems 4800 MALDI-TOF/TOF analyzer
to identify with high sensitivity and high resolution biomarkers in several
types of cancer and other diseases. Examples with regard to technological
challenges as well as potential solutions will be presented as well.
4:30 A Native Antigen "Reverse Capture" Microarray Platform for
Autoantibody Profiling and Biomarker Discovery
Brian Liu, M.D., Assistant Professor, Urology, Brigham and Women’s Hospital Identification of antigens and the detection of autoantibody
reactivity are useful in biomarker discovery and for explaining the role of
important biochemical pathways in disease. Despite all of their potential
advantages, the main challenge to working with autoantibodies is their
sensitivity. Nevertheless, proteomics may hold the key to overcoming this
limitation by providing the means to multiplex. To date, studies of
antigen-autoantibody reactivity using microarrays have relied on recombinant
proteins or synthetic peptides as arrayed features. However, recombinant
proteins and/or peptides may fail to accurately detect autoantibody binding due
to the lack of proper PTMs. We now describe the use of a native antigen
"reverse capture" platform that facilitates the autoantibody
reactivities to native antigens. As proof-of-concept, we will describe the use
of our platform, along with appropriate bioinformatics, for identifying
disease-associated signatures in urologic diseases.
