Beyond Talking – Communicating Discussion Tables
Wednesday, June 11 @ 7:00 AM

Time has been designated for facilitated discussion groups with specific themes that intersect the boundaries of developing genomic tools to therapies. Join conference participants over a light continental breakfast to focus on a topic, exchange ideas, information, experiences, and develop future collaborations.

Table One
Systems Biology Technologies for Mapping Key Networks and Pathways 
Host: Jeffrey Falk, Ph.D., Director of Technology Applications, Molecular Biology, Aviva Systems Biology
Discussion points:

• ChIP-on-ChIP

• miRNA

• mRNA Expression

• Mass Spec

• Next Generation Sequencing 

Table Two
In Vivo Delivery of RNAi Therapeutics
Host: Johannes Fruehauf , M.D., Ph.D., Vice President, Research, Cequent Pharmaceuticals Inc.
The approach to in vivo delivery of RNAi-based therapy is driven by both the biology of the system and the chemistry of the therapeutic compound. This discussion provides an overview of the different approaches for in vivo delivery of RNAi, elaborating on the various biological alternatives.
Discussion points:

• In vivo delivery of therapeutic siRNA compounds

• Viral versus non-viral methods of delivery

• Bacterial systems for RNAi delivery 

Table Three
Molecular Manipulations in the Nervous System
Carol M. Troy, M.D., Ph.D., Associate Professor, Columbia University
The nervous system poses special problems of access, crossing the blood-brain barrier and of dealing with post-mitotic cells. Many acute and chronic neurologic diseases could benefit from molecular manipulations using an siRNA approach but is this actually feasible as a therapeutic avenue?
Discussion topics: 

• Acute vs chronic knockdown approaches – what is the effect of perpetual knockdown of gene expression in a post-mitotic neuron?

• Delivery routes: what is the best way to get siRNA to the CNS?

• Delivery agents: viral vs. non-viral

Table Four
Applying Genomics in Biomarker Discovery 
Host: Dan Li, Ph.D., Principle Research Scientist, Informatics, Integrative Biology, Eli Lilly and Company
Biomarkers enable drug discovery process in both pre-clinical and clinical development. Many organizations are investing in new technology and increasing resources in biomarker discovery and validation. In the last several years, we have witnessed tremendous progress in developing and applying genomics approaches to develop biomarkers for disease diagnosis, prognosis, drug activity and toxicity. However, challenges remain in genomics-based biomarker discovery with respect to both methodology development and application in clinic. 
Discussion points: 

• Methodology in derive gene signature biomarkers from microarray data 

• Predict in vivo drug responses using biomarkers developed from in vitro 

• Single gene markers vs. gene signatures 

• Is it practical to apply gene signature biomarkers in clinic 

• Toxicogenomics: where should the gene signature markers be used

Table Five
Genetic Testing Laboratories: Working in the ‘Clear As Mud’ Regulatory Environment
Host: C. Anne Pontius, Senior Director, Quality Systems, Expression Analysis, Inc.
Share your accomplishments and vent your frustrations with the over/under (your choice) genetic testing regulatory environment.
Discussion points: 

• CLIA is round – genetic testing is square

• IVDMIA’s – where is the FDA finger pointed

• Independent laboratories ‘support’ GLP

Table Six
Public Policy, Regulation, & Payers Requirements for Personalized Medicine
Host: Patrick F. Terry, Director of Industry & Government Relations, Genomic Health, Inc.
Discussion points:

• What is happening in Congress, the Administration, and Payor community and how you can influence the dialog?

• What proposed solutions are emerging and will they be good for your business?

• What will happen with the dynamics of “data translation” and direct to consumer information when it turns into actionable diagnostics?

• When and by what mechanism will the “consumer movement” engage personalized medicine?

• Discuss the opportunities and challenges for predictive, preventive, and personalized testing.

Table Seven
Proving Value in Sound Bites: How to Communicate with Senior Management on the Topic of Systems Biology
Host: David de Graaf, Ph.D., Director, Systems Biology, Pfizer Inc.
Discussion points: 

• What is the elevator pitch for Systems Biology?

• What are the public success stories we can share?

• What is the target group for Systems Biology in a pharmaceutical organization?

• What are the minimum requirements for a Systems Biology Group in pharma and/or biotech?

Table Eight
RNAi Therapeutics: Successes and Challenges with in Vivo Delivery
Host: Dmitry Samarsky, Ph.D., Vice President of Technology Development, RXi Pharmaceuticals
RNAi offers a novel approach to the drug development process because RNAi compounds can potentially be designed to target any one of the thousands of human genes. The key to therapeutic success with RNAi lies in delivering intact RNAi compounds to the target tissue and the interior of the target cells.
Discussion points:

• Currently used approaches for delivery of therapeutic RNAi compounds

• Systemic vs. local delivery: advantages and disadvantages

• Future directions for RNAi in vivo delivery

Table Nine
Realities of microRNA-Based Therapeutics
Host: Irena Ivanovska, Senior Research Biologist, Rosetta Inpharmatics, a wholly owned subsidiary of Merck and Co., Inc.
Since their discovery less than a decade ago, microRNAs have quickly been recognized as important modulators of many biological functions, valuable tools for studying biological networks and processes and as potentially useful and novel therapeutics and biomarkers. As with most exciting new discoveries, translating potential utility into practical value in the clinic is often a difficult path. Will microRNAs prove different?
Discussion points:

• What is the best method for microRNA delivery? 

• What are the most likely diseases to benefit from microRNAs? 

• microRNAs or anti-miRs? 

• Is targeting multiple genes a benefit or a liability?

Table Ten
Bridging Gene Actions and Developmental Plan Using Statistics
Host: Rongling Wu, Ph.D., Professor, University of Florida Research Foundation, and Professor, Statistics, University of Florida, Gainesville
Every living entity from unicellular organisms to humans undergoes developmental changes in its size and shape during lifetime. Genes are thought to play a pivotal role in shaping the pattern of development and directing the organism to respond to changing environments in a coordinated manner. The identification of these underlying genes is of paramount importance in agricultural, biological and health sciences, but has been a long-standing challenge that attracts the interest of top scientists in the world. We will discuss statistical designs and models that can be used to detect and map genes responsible for the program and plan of development. More specifically, the following topics can be mentioned:
Discussion points:

• Statistical models for mapping complex traits,

• Gene identification from quantitative trait loci (QTL) to quantitative trait nucleotides

• Functional mapping of developmental trajectories,

• Effects of expression QTL and imprinting QTL on development and disease progression

• Genome-genome interactions for dynamic traits

Table Eleven
The Replication Fork Protection Complex 
Host: William Kaufmann, Ph.D., Professor, Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill
During DNA replication the parental template stands are denatured so that DNA polymerases can synthesize new daughter strands to generate two daughter chromatids. Template strands may be damaged by endogenous or exogenous stressors, and such template damage will impede or arrest DNA synthesis. Tight protein binding to DNA and unusual DNA structures such as triplexes and quadriplexes may also impede DNA synthesis. Cells respond to stalled or arrested replication forks with activation of a checkpoint that inhibits the initiation of DNA synthesis at replicon origins and slows the rate of DNA chain elongation in active replicons. A complex of two proteins, Timeless and Tipin, serves to mediate signaling in the intra-S checkpoint. New studies suggest that the Timeless/Tipin complex also stabilizes stalled replication forks to prevent fork collapse and formation of carcinogenic or lethal chromosomal aberrations. 
Discussion points: 

• This discussion will focus on biological significance of the Timeless/Tipin replication fork protection complex. 

• Inactivation of the human replication fork protection complex attenuates intra-S checkpoint response to ultraviolet radiation-induced DNA damage and causes severe chromosomal damage

• A promising treatment for cancer is to enhance the lethality of standard chemotherapy and radiation by inactivation of the replication fork protection complex 

Table Twelve
What do "Experimental Biologists" Want and/or Expect from Systems Biology?
Host: Carmen Molina-Paris, Ph.D., Lecturer, Applied Mathematics, University of Leeds
As a physicist/applied mathematician I hope that a "systems biology approach to biology" can provide experimental biology with the framework that mathematics gave to physics since the early work of Isaac Newton, and more recently with General Relativity and Quantum Mechanics. A framework within which Theories are formulated: theories such as Classical Mechanics, General Relativity and Quantum Mechanics. These theories tell us how "objects" behave and move. For example, classical mechanics is good to understand the motion of a tennis ball on the surface of the earth; quantum mechanics is good to understand and describe the atomic structure of the hydrogen atom; general relativity is good to understand the isotropy and homogeneity of our observable universe.
Discussion points:

• Do we agree on the definition of systems biology? What is that definition?

• Do we believe such theories exist for biology?

• How can we test the validity of those theories (if they exist)

• How can mathematics (modeling, in general) be of most help to systems biology?

Table Thirteen
Using Systems Biology to Understand and Model Disease Causation
Host: Fredric Young, Ph.D., Chief Scientist, Biophysics, Vicus Therapeutics Inc. 
Attempts to understand the genetic cause of complex diseases has led to the suggestion that diseases are emergent properties of molecular networks. The relationship between genes and disease causality from the standpoint of emergence can be understood from the perspective of a three level hierarchical model of biological function. This has implications for genome and HAP map based approaches for understanding human disease and assessing disease risk based on genetic profiling.
Discussion points: 

• Diseases as Emergent Properties of Perturbed Molecular Networks

• Unifying the Various Hypotheses about the Genetic and epigenetic Basis of Disease

• Implications of the Systems View of Disease for Personalized Medicine and SNP Based Risk Assessment

Table Fourteen
The Future of Biomarkers in Pharma R&D
Host: Colin Williams, Thomson Scientific
Biomarkers are often regarded as a tool to increase efficiency in Drug research, whilst there have been some significant successes so far, these are still few in number. This discussion is around how Pharma companies, and regulatory bodies, need to adapt to maximize the potential shown in using Biomarkers to enhance Drug research.
Discussion points:

• Where are Biomarkers most critical in Pharma R&D, Discovery? Clinical Trials?

• What are the key challenges facing Pharma companies in maximizing the potential of Biomarkers?

• What role will regulatory authorities, such as the FDA, play in the development of the use of Biomarkers?

• How will Pharma companies need to adapt to maximize the potential that utilizing Biomarkers in Drug discovery has shown to date?

Table Fifteen
Collaboration/Drug Discovery & Development
Host: Ting-Chao Chou, Ph.D., Director, Preclinical Pharmacology Core, Molecular Pharmacology & Chemistry Program, Memorial Sloan-Kettering Cancer Center
Drug discovery is an art rather than screening. It requires sound analysis and judgment. One needs to do things differently, not just following the routine, especially at fundamental/conceptual levels. Basic biomedical research, although it is very important, is mainly for “knowledge” which in most cases is far away from drug discovery. Efficient drug discovery should use highly focused, practical, economical, efficient, mission-oriented “team-work”. To remain efficient and competitive, it is essential to separate “basic research” (for knowledge) from “drug discovery” (for efficacy and safety). Using the unified theory of the mass-action law (i.e., the median-effect principle) allows small-size experimentation, increased efficiency and computerized simulation to constrain the costs and to conserve animals. 
Discussion points:

• Does mechanistic basic research lead to easier drug discovery?

• What are the two most important things for a new drug?

• Is it possible to draw a specific curve for only two data points? How?

• What is the “additive effect” of two drugs? What is Synergy?

• How the unified theory for the median-effect principle of the mass-action law leads to saving time and efforts, conserve animals, and reduce the cost when conducting small-size experimentation.

• Why pharmacokinetics for drug discovery? How useful is it?

• Is high-throughput technology or combinatory chemistry the way for future drug discovery?