Day 2

Tuesday, August 30

8:00 Morning Coffee and 3-D Tissue ThinkTanks
Jump Start Your Day with Java and Jive
Back by popular demdand! Time has been designated for facilitated interactive discussion in groups with specific themes. This unique opportunity allows conference participants to focus on a topic in depth to exchange ideas, information, experiences, and develop future collaborations.
Suggested Topics for Discussion:
• Engineering More in Vivo Physiological Environments
• Creating Higher Throughput 
• Cell Source Considerations
• 2-D vs. 3-D Advantages for Drug Discovery
• Cultured Cells vs. Tissue

Applications in Drug Discovery

9:00 Chair's Remarks
Dr. Angela Cacace, Senior Research Investigator II, Lead Discovery & Profiling, Bristol-Myers Squibb Co.

9:05 Tissue Model Mechanics for Drug Discovery
Dr. Tetsuro Wakatsuki, Chief Scientist, Research & Development, InvivoSciences LLC 
We have developed a drug screening method based on cellular responses that produce mechanical changes in biological tissue constructs cultivated in 96-well plates. The tissue constructs can be assembled to provide models for specific disease conditions, e.g., elevated contractility of vascular smooth muscle cells in hypertension or fibrosis and cardiovascular remodeling that lead to congestive heart failure and diastolic dysfunction or scar formation during wound healing. Phenotype-based reconstituted tissue technology is used both to validate targets and to optimize leads in one step. InvivoSciences' phenotype-based approach minimizes unrelated and invalid leads and protein targets at very early stages of the drug discovery process. This makes the drug discovery process faster, more focused, and more productive.

9:35 Three Dimensional Tumor Models for Drug Discovery in Prostate Cancer
Dr. Norman Maitland, Chief Scientific Officer, Pro-Cure Therapeutics 
Carcinoma of the prostate gland is the second most common cause of cancer death amongst males in the developed world. Current cell-based models for drug discovery in the field of oncology have a number of shortcomings due to alterations in gene expression from immortalization and prolonged culture; lack of clinical data and matched normal tissue. The use of monolayer cultures does not accurately reflect the behavior of cells in vivo. In this talk, I will describe how we have applied proprietary technology to develop a number of new models including 3-dimensional solid tumor models, for drug discovery in the field of urogenital cancer which bear a much closer resemblance both morphologically and functionally to solid tumors found in patients.

10:05 Three-Dimensional Human Tissue Models for Drug Discovery and Therapeutic Applications for Infectious Disease
Dr. Cheryl Nickerson, Associate Professor, Microbiology and Immunology, Tulane University Health Sciences Center 
Lack of in vitro cell culture model systems that mimic human physiological responses are a major barrier in the development and testing of new drugs and therapeutics against infectious disease. Our laboratory is a leader in engineering biologically meaningful 3-D human tissue culture models to provide new opportunities for drug development and other therapeutics to treat infectious disease. Specifically, we have used innovative suspension culture technology to establish 3-D cultures of human cells and tissues that more accurately model in vivo tissues and thus are more relevant to the complex environment encountered by pathogens during the natural course of infection. Previously published findings from our laboratory have demonstrated that our 3-D models respond to infection in a manner that is more reflective of an in vivo infection. These 3-D tissue models serve as an important high throughput platform technology for the development of novel therapeutic and diagnostic strategies for the prevention and treatment of human infectious disease, including protection against biological warfare agents.

10:35 Coffee Break, Last Chance to View Posters and Exhibits 

11:15 Cell and Animal Model Based Respirometric Screening Technology (RST) for ADME-Tox Screening 
Dr. James Hynes, Senior Resident Scientist, Assay Development, Luxcel Biosciences 
RST is based on fluorescence quenching and allows monitoring of oxygen consumption by cells, organisms and oxygen-dependent enzymes. RST has a diverse range of key applications in drug discovery including: direct, high-throughput analysis of mitochondrial function and activity of the electron transport chain, studies of mechanisms of toxicity and apoptosis; cell metabolic responses and metabolic profiling, parallel cell and animal-based 
screening of compound libraries and viability assays. Luxcel recently announced the expansion of an existing R&D collaboration with Pfizer, Groton, US. Data from this collaboration will be discussed.

11:45 Investigations on the Function and Regulation of the Tight Junction Protein Claudin-1 in Breast Tumorigenesis
Dr. Robert R. Macek, Scientist Cell Biology, Pharma Research Penzberg, Roche Diagnostics GmbH
Recently, claudin-1 has been identified as a major constituent of the tight junction complex and claudin-1 is lost or downregulated in most in vitro breast tumor cell models. Genetic mutations were not identified to be responsible for this loss of expression. Reexpression of claudin-1 in claudin-1 negative breast tumor cells results in correct membrane homing of this 4-transmembrane protein. In order to evaluate its cell physiological role, we reexpressed claudin-1 by retroviral transduction of claudin-1 negative MDA-MB 361 breast cancer cells. The effector function of claudin-1 was investi-gated by the analysis of TJ permeability of confluent cell monolayers and apoptosis induction in breast tumor spheroids in 3D suspension culture. Reepression and membrane homing of claudin-1 decreased the paracellular flux rate and increased apoptosis in the tumor spheroids. This cell death was present primarily in the spheroid core regions. Our findings support the hypothesis that functional tight junctions might limit nutrient and growth factor supply in tumors. Therefore, the loss of claudin-1 expression or its altered homing (membrane versus cytoplasma) might be an important step during the process of breast tumor development. 

12:15 Close of Conference