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THURSDAY, FEBRUARY 26 

7:20 am Plenary Keynote Introduction

7:30 PLENARY KEYNOTE 
Tissue Engineering Strategies for Musculoskeletal Regenerative Medicine in Civilian and Military Applications
Michael J. Yaszemski, M.D., Ph.D., Brigadier General, United States Air Force Reserves; Professor, Orthopedic Surgery and Biomedical Engineering, College of Medicine, Mayo Clinic
Tissue regeneration via tissue engineering strategies requires some combination of cells, a scaffold upon which the cells can attach and express their phenotypic function, and signaling molecules to direct the cells down the desired differentiation path. This cellular component often includes stem cells. This lecture will present current concepts regarding musculoskeletal tissue regeneration and the issues to be considered for its translation to clinical practice, as well as the unique reconstructive challenges encountered in combat injuries.

EPIGENETICS AND MICRORNA: Finding Pathways to Treatment 

8:25 Chairperson’s Remarks 
Dalia Cohen, Ph.D., Chief Scientific Officer, Rosetta Genomics Inc. and Enal Razvi, Ph.D., System Biosciences SBI

8:30 MicroRNAs in Development and Cancer
Frank J. Slack, Ph.D., Associate Professor, Molecular Cellular & Developmental Biology, Yale University 
MicroRNAs are small non-coding RNAs that regulate gene expression to control important aspects of development and metabolism such as cell differentiation, apoptosis and lifespan. let-7 encodes a microRNA implicated in human cancer. Specifically, human let-7 is poorly expressed or deleted in lung cancer, and over-expression of let-7 in lung cancer cells inhibits their growth, demonstrating a role for let-7 as a tumor suppressor in lung tissue. let-7 is expressed in the developing mammalian lung and regulates the expression of important oncogenes implicated in lung cancer, suggesting a mechanism for let-7’s involvement in cancer. We are focused on the role of let-7 and other oncomirs in regulating proto-oncogene expression during development and cancer, and on using miRNAs to suppress tumorigenesis.

9:00 Integrative Genomics and Epigenomics; Markers and Mechanisms 
Joseph F. Costello, Ph.D., Associate Professor, Karen Osney Brownstein Endowed Chair in Molecular Neuro-Oncology, University of California San Francisco 
A major challenge for the future is to understand how genomic and epigenomic aberrations cooperate directly or indirectly to develop the pathophysiologies that define human malignancies. Epigenetic mechanisms can cause genomic alterations, and genomic aberrations also can influence the cancer epigenome. Given the extensive genetic and epigenetic alterations in any given tumor, integrative analyses thus represent a new kind of filtering approach to cull passenger alterations from those that are drivers of tumorigenesis, and an improved approach to identify predictive DNA markers with clinical utility. Emerging technologies for increasingly comprehensive analyses of tumor genomes and epigenomes will be essential in these efforts.

9:30 Computational Methods for Analysis of Cellular Functions and Pathways Collectively Targeted by Differentially Expressed microRNA
Yuriy Gusev, Ph.D., Assistant Professor, Surgery & Adjunct Assistant Professor, Institute for Breast Health, University of Oklahoma 
Two recent articles published by our team from the University of Oklahoma Health Sciences Center (OUHSC) outlined a strategy for addressing the data interpretation challenges faced by researchers profiling miRNAs aberrantly expressed in human cancers. Advances in methods for profiling the microRNAome – including microarrays, rt-PCR, and micro-beads – have resulted in the subsequent downstream challenge of interpreting the regulatory impact of differentially expressed miRNAs. To directly address this challenge, our OUHSC team has developed and tested computational strategy for prioritizing lists of miRNA targets using combinatorial enrichment analysis and performing a detailed analysis of the biological functions, diseases processes, toxicological responses, signaling and metabolic pathways, and drugs most significantly associated with those miRNA targets. By using Ingenuity Pathways Analysis (IPA) to perform an in-depth analysis of genes that are collectively targeted by aberrantly expressed miRNAs in particular cancer (pancreatic, breast, colon, lung, lymphoma and liver), we established functional links between cancer-related processes and miRNA expression, identified miRNA targets that are known tissue-specific biomarkers of cancer, and narrowed in on pathways specifically to each type of cancer that were enriched for miRNA targets. The Ingenuity Knowledge Base further enabled us to perform a comparative analysis of functional predictions with what is already known about these cancers. We found a remarkable correlation in terms of affected signaling pathways and targets of known anticancer drugs. This resulted in novel computational insights into possible collective regulatory function of co-expressed miRNAs providing a clear path for follow up experiments.

10:45 Poster Competition Refreshment Break & Raffles in the Exhibit Hall

11:30 Epigenetic Silencing of miR-342 in Colorectal Cancer
Muneesh Tewari, M.D., Ph.D., Assistant Member, Human Biology Division, Fred Hutchinson Cancer Research Center
MicroRNAs (miRNAs) are small (approximately 22 nt in size) regulatory RNAs that play important roles in cancer development and progression. We discovered that miR-342, an intronic miRNA, is suppressed in colorectal cancer via epigenetic silencing of its host gene’s promoter. Furthermore, re-expression of miR-342 in colorectal cells in culture triggered apoptosis, suggesting that a function of miR-342 silencing during carcinogenesis is suppression of programmed cell death. The talk will present these results and discuss potential directions for future research.

12:00pm Diagnostic and Therapeutic MicroRNA Strategies in Ovarian Cancer 
Lin Zhang, Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania School of Medicine 
miRNAs are ~22 nucleotide non-coding RNAs, which negatively regulate gene expression in a sequence-specific manner. Increasing evidence indicates that miRNAs are key regulators of various fundamental biological processes. We have reported that miRNAs exhibit genomic alterations at high frequency and their expression is remarkably deregulated in ovarian cancer, strongly suggesting that miRNAs are involved in the initiation and progression of this disease. Indeed, our recent studies indicate that miRNA-based method is a novel strategy with strong potential application to human ovarian cancer in early detection, diagnosis and treatment.

12:30 Luncheon Presentation The NanoString nCounter System: A Highly Sensitive, Digital Technology for Multiplexed Measurement of Gene Expression Without Reverse Transcription or PCR  Gary Geiss Ph.D., Principal Scientist, NanoString Technologies We describe a novel technology, the NanoString nCounter Analysis System, that captures and counts individual mRNA transcripts. Advantages over existing platforms include direct measurement of mRNA expression levels without enzymatic reactions or bias, sensitivity coupled with high multiplex capability, and digital readout.

Sponsored by

1:00 Luncheon Presentation  Analysis of Genome-wide Genotyping Data for Copy Number Variation in Breast Cancer Aubree Hoover, Senior Product Manager, Rosetta Biosoftware Altered copy number of genes and regulatory regions of the genome can affect human health. Analysis of copy number variation (CNV) is of interest in the context of cancer research. High-density single nucleotide polymorphism (SNP) arrays generate intensity based data which can be analyzed for CNV. Using intensity data from Affymetrix® SNP arrays CNV was assessed for breast cancer samples. Data were imported into the Rosetta Syllego system and analyzed for CNV. Results were stored in the Syllego database and evaluated with built-in data viewers. The workshop will discuss the results of this analysis and how the Syllego system simplifies transfer, visualization, interpretation, and sharing of data with colleagues.

Sponsored by

1:30 Plenary Keynote Introduction 

1:40 Plenary Keynote 
Engineering Cells to Death 
James A. Wells, Ph.D., Professor and Chair of Pharmaceutical Chemistry, and Professor of Cellular & Molecular Pharmacology, University of California, San Francisco
Apoptosis, or programmed cell death, represents an ultimate fate decision in cell biology. This process is critical for cellular differentiation and remodeling of tissues, and for anti-viral and anti-tumor defense. The study of apoptotic pathways has important ramifications for determining what is critical for cellular homeostasis, and for the development of potential anti-cancer therapeutics. A distinct molecular feature of apoptosis is the widespread but controlled cellular proteolysis, that is predominantly mediated by eight members of the caspase family of cysteine proteases. These enzymes are like demolition experts that cleave protein targets critical for cellular life. We have designed new enzymes, and antibodies, and small molecules to study and activate individual caspases and the proteins they cleave. For example, a robust proteomic method for global profiling of proteolysis (“degradomics”) in cells has been developed. Key to this is an engineered enzyme, subtiligase, that permits selective labeling and enrichment for the protein N-termini created as a result of proteolysis. Using this approach we have already identified >300 caspase substrates from Jurkat cells that were induced to undergo apoptosis by treatment with the chemotherapeutic agent etoposide. The proteins fall into a wide range of functional classes, and reveal much about the molecular components, logic, and timed sequence of events that drive a cell from life to death. We believe these engineered enzymes and proteomic approaches will be useful for characterizing the proteolysis of apoptosis induced by various agents or in different cell types, and will be generally useful for dissecting protease signaling pathways.

2:25 Plenary Keynote 
The Brave New World of Personalized Medicine: The Experimental Man Project, One Man Takes the Ultimate High-Tech Exam
David Ewing Duncan, Chief Correspondent, NPR Talk’s “Biotech Nation” and Best Selling Author “Masterminds”
This focus of this presentation will be on "Creative Disruptions", and will demonstrate the walking scientific response to the question: "Can they really do that?" The most important and controversial topics of today’s scientific research will be discussed, from stem cells and synthetic biology, to rising drug prices and reforming the FDA. Recently, there has been attention on science’s most significant story: a species’ potential to self-evolve. As the founder of the independent BioAgenda Institute for Life Science Studies and, more recently, as the founder of the new Center for Life Science Policy at UC Berkeley, the passion for what comes next after new technologies appear will be explored -- what happens in business, politics, science, philosophy, the media, the arts, and to society as a whole.

3:05 Ice Cream Refreshment Break in the Exhibit Hall with BEST OF SHOW AWARDS (Last Chance for Viewing Exhibits & Posters)

EVALUATING TARGETS FOR CANCER

3:55 Chairperson’s Remarks
Ulrik B. Nielsen, Ph.D., Vice President, Research, Merrimack Pharmaceuticals

4:00 Systems Optimization of ErbB-Targeted Therapeutics: Development of an Anti-ErbB3 Monoclonal Antibody
Ulrik B. Nielsen, Ph.D., Vice President, Research, Merrimack Pharmaceuticals 
Computational biology is improving our understanding of complex biological systems. Using very large biological datasets of cell signaling, we have constructed detailed, mechanistic models. These may be used to predict network responses to targeted therapeutics such as monoclonal antibodies and small molecule inhibitors. Using the ErbB signaling network as an example, we will present how simulation proposed MM-121, a monoclonal anti-ErbB3 antibody, as a potentially superior approach current therapies.

4:30 Oncology Target-Disease Linkage through Pathway Profiling
Lihua Yu, Principal Scientist, Cancer Bioscience, AstraZeneca PLC 
One of the key challenges to the successful development of novel oncology agents is to identify disease settings most likely to see patient response. The explosion of molecular profiling data has provided us unprecedented opportunity to further our understanding of diseases at molecular level and to associate cancer pathways with disease subtypes. We will discuss several recent examples to illustrate how we use pathway-based approaches to establish oncology target-disease linkage.

5:00 Evaluation of Molecular Pathway Biomarkers of Novel Cancer Therapeutics
Sherry X. Yang, M.D., Ph.D, Chief of Nat’l Clinical Target Validation Laboratory, Division of Cancer Treatment and Diagnosis, National Cancer Institute
The talk will focus on the use of gene expression profiling approach for identification of molecular pathways in response to small molecule inhibitor of poly(ADP-ribose) polymerases in combination with chemotherapeutics, and to anti-angiogenesis agents. How the approach that was utilized for evaluation of cancer targets will be discussed and reviewed. In addition, validation and potential application of the identified pathway biomarkers will be discussed.

5:30 Epitomics: Individualized Immunoprofiling of Cancer-Specific Circulating Antibodies on Protein Microarrays of Tumor Associated Antigens
Michael A. Tainsky, Barbara & Fred Erb Professor of Cancer Genetics, Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine
The humoral immune response is an exquisite biosensor of novel proteins expressed by tumor cells. Panels of tumor antigens could provide a sensitive and specific multianalyte immunoassay for the presymptomatic of cancer. Using a high-throughput antigen cloning method, a panel of epitopes/antigens have been isolated that react with autoantibodies to tumor proteins in the serum of patients with cancer. The binding properties of these serum antitumor antibodies on microarrays and advanced bioinformatics tools led to a panel of diagnostic antigens. There are numerous advantages of employing serum antibodies as the analytes, not the least of which is the ability to readily adapt these assays to standard clinical platforms and their application to personalized immunotherapy. Early detection using panels of tumor antigens will lead to individualized interventions based on each specific immunoprofile. We envision that the early detection of cancer using immunoassays against tumor associated antigens will define a specific panel of antigens suitable for a personalized cancer vaccine for the test subject. In this fashion the earliest cancers can be eradicated with a vaccine prior to the formation of a sizable mass.

6:00 Close of Day

Overview | Day 1 | Day 2 | Day 3 | Download Brochure | Breakout Discussions

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