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(SC1) Biomarkers are Us: Interactive Short Course on How Biomarkers Will
Impact the Field of Oncology
Moderator: Jorge A. León, Ph.D., President, Leomics Consulting
Experts in oncology will be invited to speak and address the following issues:
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What is a biomarker and what does it have to comply with?
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Where do they come from?
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What is a good biomarker?
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How do you validate and implement a biomarker?
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Case studies in breast, lung, ovarian, bladder cancer
(SC2) The Challenge of the Blood-Brain Barrier – A Medicinal Chemisrty Perspective
Douglas K. Spracklin, Ph.D., Senior Principal Scientist, CNS Drug Metabolism, Pfizer Inc.
Ellen Q. Wang, Ph.D., Senior Principal Scientist, Pharmacokinetics, Dynamics and Metabolism, Pfizer Global
Research and Development
In this course you will learn…
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An introduction to the physiology of the blood-brain barrier
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In vitro methods for predicting BBB permeability
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In vivo methods for measuring brain exposure and/or target occupancy
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Case studies & applications
(SC3) ADMET CASE STUDIES FROM A
MEDICINAL CHEMISTRY PERSPECTIVE
10:15 Introduction & Welcome
Philip S. Burton, Ph.D., Chief Executive & Scientific
Officer, ADMETRx, Inc.
10:20 In Vitro ADME Assays:
Strategic Application to Drug Discovery
Dhiren R. Thakker, Ph.D., Ferguson Distinguished Professor
and Associate Dean, Research and Graduate Education, School
of Pharmacy, UNC-Chapel Hill
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Why ADME assays in drug
discovery?
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Strategic use of in vitro
ADME assays and preclinical pharmacokinetic studies in
drug discovery
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Current status of ADME in drug
discovery and future developments
11:00 Solubility, Data Integration,
in Vitro/in Vivo Correlations
Philip S. Burton, Ph.D., Chief Executive & Scientific
Officer, ADMETRx, Inc.
Solubility evaluation models
Extrapolating in vitro
data to in vivo performance
11:40 Coffee Break
12:00pm In Vitro Toxicity
Assays That Have in Vivo Relevance
James McKim, Ph.D., DABT, President & Chief Scientific
Officer, CeeTox, Inc.
12:40 Case Study: Impact of
Structure and Physchem Properties on Oral Delivery of
Antivirals
Gail L Strong, Ph.D., Director, Pharmaceutical Sciences,
Theravance, Inc.
1:00 Q&A
1:15 End of Course
(SC4) THE EPIGENETIC STEM CELL SIGNATURE
10:15
Introduction
Mark E. Levenstein, Ph.D., Research Scientist, WiCell
Research Institute
10:35
DNA Methylation
Identification of Key Pathways and Biomarkers Involved in
Human Stem Cell Differentiation by Decoding Promoter
Methylation Patterns in Human ES Cells
Jeffrey Falk, Ph.D., Director of Technology
Applications, Molecular Biology, Aviva Systems Biology
Key pathways and biomarkers involved in human stem cell
differentiation (hES) were identified using a novel promoter
array technology, ChIP-DSL (Chromatin Immunoprecipitation
DNA Selection and Ligation), to map hES cell promoter
methylation patterns in native hES cells and in hES cells at
various stages of differentiation.
11:10
Transcriptional Profiling of Human Embryonic Stem Cell
Differentiation Towards Endothelial and Cardiomyocyte
Lineages
Kitch Wilson,M.D.,Radiology,Stanford University Medical
Center
Our lab is interested in stem cell therapies for
cardiovascular disease, and we have developed protocols for
in vitro differentiation of hESCs into endothelial and
cardiomyocyte cells. While significant progress has been
made in understanding the genomics of hESCs, less is known
about the global gene expression changes that occur when
these cells differentiate toward various lineages. To better
understand these transcriptional changes, we performed
microarray analysis of cells at different points in the
differentiation process. In my talk I will present our
findings and discuss the current understanding of the
molecular networks that drive differentiation of hESCs
towards endothelial and cardiac fates.
11:45
Refreshment Break
12:00
Control of Lung and Mammary Stem and Progenitor Cell Cycle
Xin-Hai
Pei, Ph.D., Research Assistant Professor, Department of
Biochemistry & Biophysics, University of North Carolina
at Chapel Hill
The INK4-cyclin/CDK-RB pathway plays the key role in
controlling G1-to-S transition and is functionally disrupted
in most, if not all types of human cancer. CDK inhibitor
p18INK4C, a haploinsufficient tumor suppressor whose
expression is inactivated or reduced in multiple types of
human cancers, is broadly expressed at high levels during
embryogenesis and in many adult tissues. Deletion of the
Ink4c gene in mice resulted in widespread hyperplasia/tumors,
including both lung and mammary glands. We found that
putative bronchioalveolar stem cells (BASCs) are expanded in
normal and tumorigenic lungs of Ink4c -/- mice. Mammary
tumors developed in Ink4c -/- mice are comprised of
predominantly luminal cells. Ink4c -/- deficiency results in
an expansion of mammary stem cells at young age, but
premature depletion in adult mice. In contrast, luminal
progenitor cells are expanded by the Ink4c loss in young
mice and maintained throughout the adulthood. We also
determined the mechanisms underlying the repression and
activation of p16INK4A, also a tukor suppressor that is
frequently mutated in wide range of human tumors, by dynamic
methylation on H3K27 and H3k4, respectively. Together, these
results led us to propose that two INK4 genes, p18INK4C and
p16INK4A, collaboratively constrain stem cell self-renewal
and progenitor cell proliferation, with p18INK4c playing a
major role in maintaining the homeostasis of stem/progenitor
cells from early embryogenesis throughout adulthood, and
p16INK4A in limiting stem/progenitor cell function during
aging.
12:35
Wrap-up
(SC5) IMMUNOLOGICAL BIOMARKERS:
“HOW TO” AND THREE CASE STUDIES
Moderator: Eric Wakshull, Ph.D., Senior Scientist/Group Leader, Development Sciences, Genentech, Inc.
Immunological Biomarkers and Methods
Annie De Groot, M.D., Chief Executive Officer, EpiVax, Inc. and Brown University
Case Study: GDNF
Michael Moxness, Ph.D., Principal Scientist Clinical Immunology, Amgen Inc.
Case Study: DR 0701
Karin Cederbrandt, Ph.D., Molecular Toxicology, AstraZeneca
Case Study: Alpha-interferon
Maxygen (invited)
Panel Discussion with Q&A
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