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2014 Archived Content

Systems Pharmacology 

Track 6 focuses on how compounds (drugs) work in the body. How are they influenced by various -omics? The practical implications of such a compound-centric approach are exciting: new targets, new screens, new markers, new understanding of drug failure mechanisms. Systems computational toolsets, including multiscale modeling, simulation, web-based platforms, etc., will be emphasized.

Final Agenda


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TUESDAY, APRIL 29


7:00 am Workshop Registration and Morning Coffee

8:00 - 11:30 Recommended Morning Pre-Conference Workshops*

Biologics, Bioassay, and Biospecimen Registration Systems

12:30 - 4:00 pm Recommended Afternoon Pre-Conference Workshops*

Determining Genome Variation and Clinical Utility

*Separate Registration Required. Click here for detailed information.


2:00 - 7:00 pm Main Conference Registration

4:00 Event Chairperson's Opening Remarks

Cindy Crowninshield, RD, LDN, Conference Director, Cambridge Healthtech Institute


4:05 PLENARY KEYNOTE SESSION 

Click here for detailed information. 


5:00 – 7:00 Welcome Reception in the Exhibit Hall with Poster Viewing

 

 


WEDNESDAY, APRIL 30

7:00 am Registration Open and Morning Coffee

8:00 Chairperson's Opening Remarks

Phillips Kuhl, Co-Founder and President, Cambridge Healthtech Institute


8:05 PLENARY KEYNOTE SESSION 

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9:00 Benjamin Franklin Award & Laureate Presentation

9:30 Best Practices Awards Program

9:45 Coffee Break in the Exhibit Hall with Poster Viewing


Modeling: Novel Tools 

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10:50 Chairperson's Remarks

Avi Ma’ayan, Ph.D., Associate Professor, Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai





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11:00 The Human Avatar: Quantitative Systems Pharmacology to Support Physician Decision Making in Neurology and Psychiatry

Hugo Geerts, Ph.D., MBA, BA, CSO, In Silico Biosciences; Adjunct Associate Professor, Perelman School of Medicine, University of Pennsylvania

CNS Quantitative Systems Pharmacology uses computer-based mechanistic modeling integrating brain network neurophysiology, functional imaging of genetics, pharmacology of drug-receptor interactions and parameterization with clinical data. A patient model (“human avatar”) can be developed accounting for polypharmacy and life history of traumatic events to help identify optimal treatments.

11:30 VisANT: An Integrative Network Platform to Connect Genes, Drugs, Diseases and Therapies

Zhenjun Hu, Ph.D., Research Associate Professor, Center for Advanced Genomic Technology, Bioinformatics Program, Boston University

With the rapid accumulation of our knowledge on diseases, disease-related genes and drug targets, network-based analysis plays an increasingly important role in systems biology, systems pharmacology and translational science. The new release of VisANT aims to provide new functions to facilitate the convenient network analysis of diseases, therapies, genes and drugs.

12:00 pm Selected Oral Poster Presentation: Individualized PK/PD Biosimulations for Precision Drug Dosing: Diabetes Mellitus

Clyde Phelix, Ph.D., Associate Professor, Biology, University of Texas San Antonio

Individualized biosimulations offer many advantages to precision medicine. Using one’s transcriptome to determine parameters of kinetic models of metabolism reanimates that individual for in silico testing. The Transcriptome-To-Metabolome™ Model is multiorgan and multicompartmental, including over 30 primary and secondary metabolic pathways and transport processes. Thus pharmacokinetics/pharmacodynamics studies can be performed in silico before treating each patient.

12:40 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own


Modeling: Cancer 

1:50 Chairperson's Remarks

Hugo Geerts, Ph.D., MBA, BA, CSO, In Silico Biosciences; Adjunct Associate Professor, Perelman School of Medicine, University of Pennsylvania


1:55 FEATURED PRESENTATION

Identifying Drug Targets from Drug-Induced Changes in Genome-Wide mRNA Expression

Avi Ma’ayan, Ph.D., Associate Professor, Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai

We collected and organized publicly available genome-wide gene expression data where hundreds of drugs were used to treat mammalian cells and changes in expression were compared to a control. We then developed computational methods that try to find the drug targets from the expression changes. We show that different steps in the analysis can contribute to approaching the right answer.


2:25 Tools for Comparison of Systematically Generated Cancer Networks vs. Literature Models

Dexter Pratt, Project Director, NDEx, Cytoscape Consortium

Cancer subtype genetic networks can be generated by systematic analysis of patient somatic mutation data. Comparison to existing models of cancer mechanisms is an important step in investigating these data-derived models. Recent work on Network Based Stratification (NBS) at the Ideker Lab will be described along with tools for network comparison under development in the NDEx project.

2:55 Integration of Text Mining and High Throughput Screening to Identify Candidate Targets for Cancer Therapy: Focus on the Autophagy Pathway

Philip L. Lorenzi, M.D., Anderson Cancer Center
Autophagy, a programmed process in which cell contents are delivered to lysosomes for degradation, appears to have both tumor-suppressive and tumor-promoting functions; both stimulation and inhibition of autophagy have been reported to induce cancer cell death, and particular genes and proteins have been associated both positively and negatively with autophagy. To provide a basis for incisive analysis of those complexities and ambiguities and to guide development of new autophagy-targeted treatments for cancer, we have compiled a comprehensive, curated inventory of autophagy modulators by integrating information from published siRNA screens, multiple pathway analysis algorithms, and extensive text-mining of the literature. The resulting inventory includes739 proteins and 385 chemicals (including drugs, small molecules, and metabolites). Because autophagy is still at an early stage of investigation, we provide extensive analysis of our sources of information and their complex relationships with each other. We conclude with a discussion of novel strategies that could potentially be used to target autophagy for cancer therapy. 


3:25 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Using Multiscale Systems Modeling to Design and Develop New Protein Therapeutics

Matthew Onsum, Ph.D., President, Silver Creek Pharmaceuticals

In this talk, I will present an approach to building multiscale systems models that capture drug pharmacokinetics and their effects on cell-signaling networks. I will then present two case studies that illustrate how these models can be used to design new therapies.

4:30 Biomarker Discovery to Predict Antitumor Activity through Systems Pharmacology in Drug Development and Cancer Therapy

Yasuhiro Funahashi, Ph.D., Senior Director, Biomarkers and Personalized Medicine Core Function Unit, Eisai, Inc.

NGS promotes molecular profiling of cancer and provides novel gene alterations to be targeted. But many cancer types cannot be caused by a single driver gene. A systematic approach based on pharmacology data combining PD and PG will be effective to identify biomarkers for anticancer agents targeting tumor microenvironments like angiogenesis inhibitors and chemotherapeutic agents.

5:00 A Pharmacogenomic View of the NCI-60 Cell Lines and Beyond

Ogan D. Abaan, Ph.D., Research Fellow, Genetics Branch, National Cancer Institute, National Institutes of Health (NIH)

In this talk, we will present findings from our next-generation sequencing efforts using the NCI-60 cell lines and the pharmacogenomic data we have generated. In addition, we will discuss some new directions we have taken to mine the sequence data.

5:30 - 6:30 Best of Show Awards Reception in the Exhibit Hall


THURSDAY, MAY 1

7:00 am Registration Open

7:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

8:00 Chairperson’s Opening Remarks

Kevin Davies, Ph.D., Vice President Business Development & Publisher C&EN, American Chemical Society; Founding Editor, Bio-IT World


8:05 PLENARY KEYNOTE SESSION 

Click here for detailed information. 


10:00 Coffee Break in the Exhibit Hall and Poster Competition Winners Announced


Modeling: Biotherapeutics 

10:30 Chairperson's Opening Remarks

John M. Burke, Ph.D., Co-Founder, President and CEO, Applied BioMath, LLC

10:35 Mechanistic Models to Guide Development of Novel Biotherapeutics

Bruce Gomes, Ph.D., Senior Translational Modeler, Novartis Institutes for BioMedical Research

Novel biotherapeutic modalities are being created at an ever-growing pace. Due to their novelty, many design parameters and questions about feasibility and safety are unknown. The “design-test-redesign” cycle is often daunting. Modeling of the basic mechanisms that apply to these novel strategies can shorten the time to produce valuable, life-saving new drugs. We explore such issues.

11:05 Systems Pharmacology: Enabling Quantitative Decision Making from Early Discovery to PhI

John M. Burke, Ph.D., Co-Founder, President and CEO, Applied BioMath, LLC

Systems Pharmacology modeling has been used successfully at several pharmaceutical companies. Here we present several case studies that saved an estimated $175M by enabling earlier quantitative decisions that could not be easily addressed by traditional methods. Unlike traditional PK/PD models, Systems Pharmacology models leverage known biophysical interactions and integrate data from a variety of sources (in vitro, in vivo and clinical). These models act as a central repository of data and knowledge of human pathomechanisms, allowing for the exploration of hypotheses that cannot be fully tested prior to dosing patients.

11:35 Turning -Omic Data into Therapeutic Insights

Ernest Fraenkel, Ph.D., Associate Professor, Biological Engineering, Massachusetts Institute of Technology

Biology has been transformed by new technologies that provide detailed descriptions of the molecular changes that occur in diseases. However, it has been difficult to use these data to reveal new therapeutic insights. I will show how specific network modeling approaches reveal previously undetected pathways linking disparate -omic observations. We have used these methods to analyze how oncogenic mutations alter signaling and transcription and to prioritize experiments aimed at discovering therapeutic targets.

12:15 pm Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing


Modeling: Drug/Dose Response 

1:55 Chairperson's Remarks

Birgit Schoeberl, Ph.D., Vice President, Research, Merrimack Pharmaceuticals


2:00 FEATURED PRESENTATION

Systems Approaches to Risk Assessment

Lawrence J. Lesko, Ph.D., FCP, Clinical Professor and Director, Center for Pharmacometrics and Systems Pharmacology, University of Florida

“Idiosyncratic” adverse drug events (ADEs) are a substantial societal burden in terms of morbidity, mortality and healthcare costs. Predicting who will suffer ADEs from what medications is extremely difficult with current observational or surveillance approaches. A new mechanistic approach to drug safety science is sorely needed. Systems approaches may address this unmet medical need.


2:30 Pharmacodynamic Characterization of Compounds in Drug Discovery

Rui-Ru Ji, Ph.D., Principal Scientist, Genomics, Bristol-Myers Squibb

The transcriptome reacts in a dose-dependent manner to compound treatment. We will present methodology and will discuss multiple applications of dose response profiling of the whole transcriptome.

Modeling: Drug Discovery 

3:00 Bringing Quantitative Systems Pharmacology into Drug Discovery: Implementation, Examples and Challenges

Sandra A.G. Visser, Ph.D., Principal Scientist, Modeling and Simulation, Merck Research Labs

Model-based drug discovery uses systems pharmacology to more quantitatively understand relations between drug exposure, target engagement, efficacy and safety for target validation; define compound properties in lead-optimization and safety margins; and predict human dose and scheduling for clinical candidates. We discuss drug discovery implementation, impact examples and challenges.

3:30 Applying Systems Biology from Bench to Bedside

Birgit Schoeberl, Ph.D., Vice President, Research, Merrimack Pharmaceuticals

We will discuss how Systems Biology can be applied throughout the drug discovery and development process: from drug target identification to therapeutic design and, ultimately, to the clinical development strategy.

4:00 Conference Adjourns

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  • Making the World's Knowledge Computable
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