Please check back for updates! |
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| Day 1 - Wednesday, November 6, 2013 |
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| 12:00 | Check In & Registration |
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| 1:00 | Welcome & Opening Remarks |
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Joint Session with 3rd Cancer Epigenetics: 3D Cell Cultures & Physiologically Relevant Model Systems
Moderator: Geoffrey Bartholomeusz, Assistant Professor & Director of the siRNA Core Facility
University of Texas MD Anderson Cancer Center |
| | FEATURED PRESENTATION |
| 1:05 | The Third Dimension for High Throughput RNAi Driven Target Identification |
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Geoffrey Bartholomeusz
Assistant Professor & Director
siRNA Screening Service
InSphero AG |
| | The tumor microenvironment is a complex 3D microenvironment. Although two-dimensional (2D) model systems have contributed to our understanding of tumor biology these models fall short of reproducing the complex and dynamic environments of the tumor. This has prompted the development of three-dimensional (3D) models. The most commonly used 3D model is the spheroid model. This model is of intermediate complexity between in-vivo tumors and monolayer cultures and takes advantage of the natural tendency of cells to aggregate. The cellular organization within spheroids emulates the heterogeneity of solid tumors with necrosis and radiation-resistant hypoxic regions. We have developed a 3D spheroid cell culture model to address our hypothesis - silencing targets that regulate tumor architecture will alter the integrity of the tumor, reduce the hypoxic state and sensitize the tumor to radiation and/or chemotherapy. We performed a high throughput RNAi screen utilizing our spheroid model in which the activation of HIF-1 was used as the readout for the selection of hits from the primary screen and alterations of hypoxic status of the inner core of the spheroid was used in the final validation and selection of the top ranked hits. Utilizing our selection criteria for this study we identified and validated 5 unique targets whose silencing alters the integrity of the spheroid architecture.
In conclusion, the features of the third dimension, hypoxia, morphology and the heterogeneous growth characteristics of spheroids not present in 2D monolayer cell cultures makes this model a necessary model for studies in tumor biology.
Benefits of study
1. Good model to be used in high throughput screening
2. Good model for target identification with clinical relevance
3. Novel therapeutic approach
4. Minimizes the use of animals in the determining the therapeutic efficacy of small molecules |
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| 1:40 | Rational Design and Interrogation of Physiologically Relevant 3D Co-culture Models |
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Jan Lichtenberg
CEO & Co-Founder
InSphero AG |
| | 3-dimensional (3D) cell culture technology enables engineering of organotypic in vitro models for drug discovery and pre-clinical safety assessment. As a tissue consists not only of a single cell type, key parameters for successful model generation are the right choice of cell types – which can be either cell lines, differentiated primary cells or stem cell-derived cells – and their relative ratios within the model. Moreover, histological structuring of 3D models and microenvironment design, including the culture medium, are important determinants of tissue engineering. The resulting models can vary substantially in complexity and resulting biological information. In the presentation we provide practical guidance for rational 3D cell model design. Application examples for the assessment of targeted immunomodulatory antibodies and the detection of idiosyncratic liver toxicity will demonstrate the importance of multi-cell type organotypic models to improve in vitro biology.
Generating 3D cell-based in-vitro models is only one step towards answers to specific biological questions. The equally important second step is the efficient and biologically relevant interrogation of these models – ideally leveraging existing assay technology and instrumentation to facilitate the implementation of 3D cell-based assays into existing workflows. A wide spectrum of currently used assay technology has been investigated, reaching from biochemical assays to histology, RNA and protein expression profiling and high-content analysis. The presentation will provide guidelines for choosing appropriate assays and for multiplexing them to gain high information content of 3D screens and to reduce overall costs.
Benefits of this presentation include practical guidance on designing 3D microtissues to correspond to the underlying biological questions and on developing robust and efficient read-out strategies. |
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| 2:05 | Validating Performance of Cytotoxicity Assays Applied to 3D Cell Culture Models |
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Terry Riss
Senior Product Specialist
Cell Health
Promega Corporation |
| | Cells cultured in 3D model systems often acquire relatively large in vivo-like structures compared to the thickness of a 2D monolayer of cells grown on standard plastic plates. Multicellular 3D culture systems containing more than one cell type and exhibiting formation of a complex extracellular matrix represent a more physiologically relevant environment, yet provide a challenge for assay chemistries originally designed for measuring events from monolayers of cells. There is an unmet need for guidelines for design and verification of convenient and effective assays useful for larger 3D microtissues. Critical factors to consider for each model system and cell type include effective penetration of detection reagents and/or complete lysis of microtissue structures using combinations of detergent and physical disruption. We will present the approach used to verify performance of the bioluminescent ATP detection assay for measuring cell viability, a caspase assay for detecting apoptosis, and cell stress assays to detect mechanisms leading to cytotoxicity. Recommendations for factors to consider when verifying performance of cell health assays on 3D culture models will be presented.
Benefits:
Attendees will learn about:
-Critical aspects to consider when using commercial assays designed for cell monolayers and attempting to apply them to 3D culture models
-The importance of knowing the stability of the marker you are trying to measure
-Methods to achieve effective lysis of microtissues
-New assay chemistries being developed to measure viability of cells in 3D cultures |
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| 2:30 | Afternoon Networking & Coffee Break |
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| | A Human Breathing Lung-on-a-chip for Drug Screening and Nanotoxicology Applications |
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Dongeun Huh
Wilf Family Term Chair & Assistant Professor
Bioengineering
University of Pennsylvania |
| | A major problem slowing the development and regulatory approval of new and safer medical products is the lack of experimental in vitro model systems that can replace costly and time-consuming animal studies by predicting drug efficacy and toxicity in humans. Here we describe a biomimetic microsystem that reconstitutes the critical functional alveolar-capillary interface of the human lung. This microdevice reproduces complex integrated organ-level responses to bacteria and inflammatory cytokines introduced into the alveolar space by inducing expression of intercellular adhesion molecule-1 (ICAM-1) on the microvascular endothelium surface, adhesion of circulating blood-borne neutrophils, their transmigration across the capillary-alveolar interface, and phagocytosis of the infectious pathogens. Using this approach, we developed novel nanotoxicology models and revealed that physiological cyclic mechanical strain greatly accentuates toxic and inflammatory responses of the lung to silica nanoparticles. Mechanical strain also enhances nanoparticle uptake by the epithelial cells and stimulates their transport into the underlying microvasculature. Importantly, similar effects of physiological breathing on nanoparticle absorption were observed in whole lung using a mouse lung ventilation-perfusion model. We also explored the potential use of this microsystem for the development of microengineered models of human lung disease for applications in drug screening. This mechanically active biomimetic microsystem represents valuable new model systems for in vitro analysis of various physiological functions and disease processes, in addition to providing low-cost alternatives to animal and clinical studies for drug screening and toxicology applications. |
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| 3:25 | A Novel Approach to Overcome Oncogenic Addiction via 3D Model Systems |
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Hakim Djaballah
Director
HTS Core Facility
Memorial Sloan-Kettering Cancer Center |
| | Classical drug discovery pathways for oncology have relied heavily on killing cancer cells; the approach has worked extremely well in some cases but not as good as predicted in others with many failures reported the clinic. Therefore, there is a sense of urgency in discovering novel small molecule therapeutics for combat cancer. We have taken an opportunistic approach looking for small molecules which would selectively revert the oncogenic addictive state of the cancer cell yielding a vulnerable phenotype; thought to be easily targetable with common chemotherapeutics agents. I will describe the approach and discuss our findings thus far with the ultimate goal of progression to the clinical.
Learning benefits include and not limited to:
1. High content assay approaches monitoring 3D cell formation in 384-well microtiter plates.
2. Screening for compounds able to reverse the cluster phenotype of 3D cells.
3. Importance of biomarkers to compare and contrast 3D cells versus those growing in 2D; critical parameter to confirm that the cell pile-up or cluster is indeed a 3D outcome. |
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| | Panel Discussion |
| 3:50 | Venture Capitalist Perspective: Considerations in Life Sciences Funding |
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| 4:35 | Day 1 of Summit Concludes |
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| Day 2 - Thursday, November 7, 2013 |
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| 8:00 | Welcoming Remarks |
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| | FEATURED PRESENTATION |
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Anthony Davies
Director
High Content Research Facility
National Center for High Content Screening and Analysis (INCHA) |
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High Content & Image-Based Screening
Moderator: Larry Sklar, Director, University of New Mexico Center for Molecular Discovery |
| 8:40 | Drug Discovery Challenges, Large and Small |
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Michelle Arkin
Associate Adjunct Professor
University of California, San Francisco |
| | The Small Molecule Discovery Center and the Center for Discovery and Innovation in Parasitic Diseases at UCSF have collaborated on several programs using high-content screens to seed drug-discovery efforts for neglected tropical diseases. The protozoan trypanosomal parasites Leishmania and T. cruzi live inside mammalian cells, cleverly evading the immune system and inhibiting apoptosis of the host cells. We have developed assays to count the trypanosomes within cultured cells, allowing us to screen for compounds that kill the parasites without inhibiting proliferation of host cells. On the other end of the size scale, we have designed a unique image-based assay for the parasitic worm (helminth) Schistosoma mansoni, the causative agent of schistosomiasis. Our goals are to monitor and quantify worm phenotypes, so that we can discover anti-helmithic compounds, characterize mechanisms-of-action, and identify biochemical targets. To define a phenotype, we collect images over time and record the worms’ morphometric features and motions. The current assay represents a rapid, ultra-high-content screen for schistosomules, and will dramatically streamline the search for new anti-helminthics. |
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| 9:05 | High-Throughput Image-Based Cell Screening |
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Bahram Jalali
Professor
Electrical Engineering Department
University of California, Los Angeles |
| | This talk will describe new fluorescent and new label-free cellular imaging techniques for cell classification with applications in medical diagnostics and drug discovery. Fluorescent Imaging using Radiofrequency-tagged Emission (FIRE) is a new approach to fluorescent imaging with sub-millisecond time resolution that is inspired by frequency division multiple access techniques used in wireless communication. Stretched-Time-Encoded Amplified Microscopy (STEAM) is inspired by fiber optical communication and uses image amplification and time stretch transform to perform phase contrast imaging at 100,000’s of cells per second. With an order of magnitude higher throughput than current state-of-the-art technologies, these two techniques identify rare cells in a large sample size and are designed for applications such as stem cell purification and liquid biopsy. |
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| 9:30 | Measuring Nuclear Translocation and Immunological Synapse Formation Using Imaging Flow Cytometry |
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Haley Pugsley
Applications Scientist
Amnis |
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| 9:55 | Morning Networking & Coffee Break |
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| 10:30 | |
Benjamin Braun
Assistant Professor
Department of Pediatrics, Hemology & Oncology
University of California, San Francisco |
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| 10:55 | Multiplex Assays for GPCR Signaling in Living Cells |
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Thomas Hughes
Associate Professor & Department Head
Department of Cell Biology & Neuroscience
Montana Molecular |
| | Cyclic Adenosine Monophosphate (cAMP) is an important intracellular second messenger in many GPCR signaling pathways. There is a wealth of evidence that the coordinated production/destruction of cAMP is tightly controlled over time and space in living cells, but most high throughput assays for cAMP involve destructive, single time point measurements. Until now, live cell, kinetic measurements of cAMP have involved genetically encoded fluorescent sensors for cAMP that convert the cAMP-dependent changes in protein kinase A (PKA) or EPAC into changes in Förster energy transfer (FRET) between two different fluorescent proteins. These sensors produce small changes in fluorescence that are useful for live cell imaging in a basic research environment, but are useless on fluorescence plate readers in a HTS effort. Further, because the donor and acceptor proteins use most of the visible spectrum they are not amenable to multiplexing with other fluorescent indicators for simultaneous detection of multiple second messengers. Here, we describe new, genetically-encoded, single fluorescent protein biosensors for cAMP that produce robust signals in living cells and can be readily multiplexed with existing Ca2+, DAG, PIP2, cGMP, or voltage sensors. The fluorescence changes are significantly larger than previous FRET-based biosensors. When used in combination with other single fluorescent protein biosensors, they provide simultaneous indicators of different G-protein pathways in living cells. These robust, multiplex assays may have potential value in drug discovery for the study of agonist-biased signaling. |
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| 11:20 | Ligand Discovery for GPCR with HT Flow Cytometry, Multiplexing, FAP Tags, and Combinatorial Libraries |
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Larry Sklar
Director
University of New Mexico Center for Molecular Discovery
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| | We have introduced several scalable approaches for multiplexing cellular targets, screening combinatorial libraries, and distinguishing among classes of ligands. These approaches identify new GPCR ligands as well as their mechanism of action and can be applied to canonical and non-canonical ligands of known as well as orphan receptors. We have focused on suspension cells using high throughput flow cytometry in conjunction with labeled ligands for GPCR or FAP-tagged GPCR (Carnegie-Mellon University) in which the fluorogen activativing protein (FAP) tag provides the fluorescence signal for resolving cell surface from internalized receptor. The FAP technology has been applied to the adrenergic receptor family, on orphan receptor, and several FAP-tagged chemokine receptors. Two FAP tags having distinguishable fluorescence can be observed simultaneously. This technology is compatible with multiplexing via cell encoding. Cell and bead-based assays using soluble receptor distinguish canonical and non-canonical ligands.
We have performed duplex screens with formylpeptide receptors (FPR1/FPR2), G protein–coupled receptors linked to acute inflammatory responses, malignant glioma stem cell metastasis, and chronic inflammation. We used mixture-based combinatorial libraries and positional scanning deconvolution to identify selective high-affinity (low nM Ki) compounds from separate libraries (Torrey Pines Institute for Molecular Studies), The most active individual compounds were functionally characterized as agonists or antagonists. The most potent FPR1 agonist and FPR2 antagonist identified to date have EC50 of 131 nM (4 nM Ki) and an IC50 of 81 nM (1 nM Ki), respectively, in intracellular Ca2+ response determinations. Comparative analyses of previous screening approaches illustrate the advantages of this approach.
Advantages: Scalable, multiplexed approaches to known and orphan GPCR; distinguishes canonical and non-canonical ligands; established workflow for deconvolution of combinatorial libraries |
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| 11:45 | Lunch on Your Own |
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Innovations in Phenotypic Screening
Moderator: Thomas Hughes, Chief Scientifc Officer, Montana Molecular & Professor, Montana State University |
| 1:30 | Laser Scanning Cytometry for Drug Discovery and Early Toxicology |
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Robert Damoiseaux
Scientific Director
Molecular Screening Shared Resource
University of California, Los Angeles |
| | The completion of the genome has left us with many available drug targets, but limited understanding of their importance in the context of health and disease. In this context, phenotypic screening is one of the most useful modalities in HTS for the discovery of novel drugs as well as target discovery and validation since only minimal knowledge about the actual players involved is necessary. Laser scanning cytometry is an excellent tool for phenotypic screening: We have taken advantage of this tool in order to screen for compounds that are potential replacements for taxol. Taxol – one of the most successful anti-cancer drugs – unfortunately does not cross the blood-brain barrier and is very difficult to synthesize which makes finding compounds with improved properties and synthesis routes a priority. We used laser scanning cytometry in order to screen directly by cell cycle in order to find such compounds. We will present results from this screening campaign in which we were able to obtain a reconfirmation rate of 86%. Moreover, most of the compound found (85%) were anti-mitotic. We will also present a novel screening methodology for genotoxic compounds: in this EPA collaboration we were able to directly quantify the DNA damage response of a living cell. We screened a subset of the ToxCast21 library utilizing laser scanning cytometry in dose response and identified various compounds with genotoxic properties. We will then discuss applications of this assay for the early detection of genotoxic liabilities of drug candidates as well as other pertinent methodologies. |
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| 2:05 | Discovery of Novel Chemical Modifiers of Metabolism Using Whole Organism Small Molecule Screening in Zebrafish |
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Anjali Nath
Postdoctoral Fellow
Harvard Medical School/Massachusetts General Hospital |
| | Commonly employed target-based approaches used in in vitro screens do not mimic the elegant orchestration of energy homeostasis that occurs in vivo. In a living organism signals originating from multiple organ systems must be integrated by beta cells in order to tightly regulate glucose levels. In an effort to discover novel small molecule tools to interrogate glucose homeostasis in vivo, we developed a high-throughput assay for measuring glucose levels in larval zebrafish. This platform allowed for the screening and discovery of novel bioactive small molecules in an intact whole organism. Analysis of the 15,000 compounds screened in our assay revealed novel small molecules that regulate glucose homeostasis and unique small molecule tools that, in the future, may provide a chemical scaffold for a new generation of anti-diabetic drugs. The use of zebrafish chemical screening to evaluate complex physiological processes is a new and emerging area with the goal of more accurately predicting how small molecules will affect complex processes such as glucose homeostasis.
Benefits:
1) Establishing a quantitative high-throughput assay to measure glucose levels. 2) Isolating novel small molecules that affect glucose levels in a manner that is unbiased to mechanism of action. 3) Discovering effective hypoglycemic agents in the complex metabolic milieu of a whole organism. 4) Ability to predict the side effects of small molecules in a whole organism at an early stage in drug development. |
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| 2:30 | TBA |
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| 255 | 3D Models For High-Throughput Drug Discovery Targeting Metastatic Cancer |
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Daniel LaBarbera
Assistant Professor of Drug Discovery and Medicinal Chemistry
University of Colorado School of Pharmacy |
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| 3:20 | Phenotypic Screening of Cells in Solution |
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Helen Ho
Field Applications Scientist
IntelliCyt Corporation |
| | New technologies, notably high content methods that make multiplexed, multi-parameter measurements on single cells, have revolutionized phenotypic screening. Complementary to target-based screening, phenotypic screening offers a more holistic view of drug discovery by integrating genetic, biochemical pathway and functional information into a systems view of diseases and potential therapies. The IntelliCyt iQue™ Screener utilizes a high throughput, flow cytometry-based detection to provide information-rich data on a cell-by-cell basis at the speed required for high throughput screening (HTS). We present a case study of how IntelliCyt® Technology has been utilized for phenotypic screening in a study assessing GFP reporters to develop Novel Acute Myeloid Leukemia (AML) therapies. |
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| 3:45 | Afternoon Networking & Coffee Break |
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| Advances in Functional Genomics & Screening |
| 4:15 | Lessons Learned: High Throughput RNAi Screening at ICCB-Longwood |
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Jennifer Smith
Assistant Director
ICCB-Longwood Screening Facility
Harvard Medical School |
| | The ICCB-Longwood Screening Facility at Harvard Medical School provides resources for investigators interested in screening small molecule, siRNA, and miRNA libraries, and has a full-time staff of expert personnel who assist investigators with assay development, lab automation, and data analysis. Following RNAi knockdown, cells are frequently subjected to additional perturbations including environmental stress, drug treatment, and microbial infection. Assays can be automated using specialized instrumentation designed for high-throughput screening and miniaturized to high-density microplates. Most RNAi screens at ICCB-L are carried out in 384-well microplate format, but the facility also supports 96-well microplate assays. Approximately half of the RNAi screens utilize a plate reader for assay quantitation, and the other half rely upon high-content imaging. Over 75 successful RNAi screens have been performed at ICCB-Longwood, resulting in many publications in prominent journals. Using analyzed data collected in our internal laboratory information system, Screensaver, we have determined that few siRNA pools score as positive across a majority of screens. Our data curation effort is now focused on gathering data from secondary, deconvolution screens of the individual duplexes to gain insight into how many duplexes individually induce the same phenotype as the corresponding duplex pool. This talk will focus on the best practices we have developed since initiating siRNA screening in 2006 and how we are continually adapting to accommodate non-standard assays. |
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| 4:40 | An Arrayed Genome Scale Lentiviral Enabled shRNA Screen Identifies Lethal & Rescuer Gene Candidates |
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Bhavneet Bhinder
Computational Analyst
Memorial Sloan-Kettering Cancer Center
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| | RNAi technology is becoming an integral tool for target discovery and validation; with perhaps the exception of only few studies published using arrayed shRNA libraries, most of the reports have been either against pooled siRNA or shRNA, or arrayed siRNA libraries. For this purpose, we have developed a workflow and performed an arrayed genome-scale shRNA lethality screen against the TRC1 library. The resulting targets would be a valuable resource of candidates towards a better understanding of cellular homeostasis. I will present and discuss our results together with the implementation of the BDA method for RNAi screening data analysis. |
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| 5:05 | TBA |
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| 5:30 | Oral Presentations from Exemplary Submitted Abstracts |
| | To be considered for an oral presentation, please submit an abstract here by October 8, 2013. Selected presentations will be based on quality of abstract and availability. Presentation slots fill up fast so please submit your abstract ASAP. |
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| 5:55 | Evening Networking Reception |
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| Day 3 - Friday, November 8, 2013 |
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| 8:00 | Welcoming Remarks |
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Stem Cells & iPS Cells
Moderator: Kelvin Lam, Founder & President, Simplex Pharma Advisors |
| | KEYNOTE PRESENTATION |
| 8:05 | Stem Cell-based Screening and Expanding Drug Target Space for Heart Failure |
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Mark Mercola
Professor and Director, Muscle Development and Regeneration Program
Sanford-Burnham Medical Research Institute
Professor
University of California, San Diego |
| | There is an urgent need for therapies that reverse the course of ventricular dysfunction in heart failure, which is a leading cause of morbidity and mortality. Our research is focused on developing High Content Screening (HCS) assays and instrumentation to discover targets and screen for molecules active in cardiac regeneration and cardiomyocyte contractility. Recent work has illustrated that functional screening of whole microRNAome libraries can be used to construct protein-protein interaction networks controlling complex disease-related biological processes. In order to screen directly for physiological function, we developed kinetic imaging cytometry, a new high content screening technology capable of optically measuring cardiomyocyte contractile calcium transients and voltage action potential kinetics and morphology using fluorescent calcium and recently developed “molecular wire” voltage probes. Using a combination of primary target-based screening coupled to secondary functional kinetic imaging cytometry screening, we identified new microRNA targets that repress contractile function in the heart and have developed a specific RNA molecule that can be delivered intravenously to halt established heart failure in a mouse pressure overload model. |
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| 8:50 | Phenotypic Screening Technologies to Identify Small Molecules That Can Reprogram Somatic Cells to iPS Cells |
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Kelvin Lam
Founder & President
Simplex Pharma Advisors
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| | It has been established in the literature that somatic cells can be reprogramed into induced pluripotent stem (iPS) cells. Since the iPS cells have self-renewal potential and have the ability to differentiate into many cell types, it could be well suited for (1) investigations lead into therapeutic potential of cell based therapies (2) studying disease model system to understand disease pathways and for (3) toxicity studies in drug discovery and development programs. Common techniques for deriving iPS cells utilize retroviruses or lentivirus. Retroviral infection randomly integrates foreign genetic material throughout a host’s genome follow by spontaneous reactivation of viral transgenes has led to tumor formation. To realize the promise of the stem cells biology, one must be able to generate iPS cells without viral transduction and transgenic modification. To achieve this goal, several groups have identified small molecules that can reprogram somatic cells to pluripotency. This discussion will highlight the significant advancement made towards achieving this major goal by employing phenotypic screening technologies and will examine the lessons learned. |
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| 9:15 | Human Induced Pluripotent Stem Cells and Patient Specific Cell Based Disease Models for Drug Discovery |
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Anne Bang
Director
Cell-Based Disease Modeling and Screening
Sanford-Burnham Medical Research Institute |
| | Patient-specific primary cells and human induced pluripotent stem cells (hiPSC) complement traditional cell-based drug discovery assays and could aid in the development of clinically useful compounds. We used patient cells to develop a phenotypic assay for muscular dystrophy that distinguishes between affected and unaffected individuals, faithfully recapitulating key molecular features of the disease. A high content screen of patient cells was conducted with the goals of identifying early treatment candidates, and probes to gain a greater understanding of underlying cellular defects. In addition, using hiPSC derived neurons, we have also conducted a high-content screen for bioactive compounds that modulate neurite outgrowth and retraction. Neurite formation plays a fundamental role in development and remodeling of neuronal networks suggesting that neurite outgrowth and retraction may be a useful phenotypic read-out to develop small-molecule probes to study how this process is altered in neurological disease. We will discuss our high content screening results and development of iPSC based models for testing of drugs on disease relevant cell types. |
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| 9:40 | High Content Screen of an Arrayed cDNA Library in the Mesenchymal Stem Cell Model Line C3H/10T1/2 |
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Patrick Collins
Scientist
Amgen |
| | The mesenchymal stem cell, capable of myogenesis, chondrogenesis, osteogenesis and adipogenesis, is the subject of intense interest for a variety of therapeutic applications. We treated sub-confluent C3H/10T1/2, a mouse mesenchymal stem cell model line, with an arrayed cDNA library comprised of 3918 clones (2921 genes) in 384 well format. To assess the impact of individual factors on adipogenesis, cells were treated with an adipogenic differentiation cocktail and incubated in the presence of those stimuli for five days. At the end of this differentiation period, cells were stained, fixed and imaged on the Perkin Elmer Opera HCS followed by image analysis, segmentation and feature extraction. One of the major challenges we faced in this screen was identification and prioritization of targets for follow up from the high content data set. To that end, we will discuss a variety of multiparametric analyses we used and the relative utility and validation rates for each. Together, our analyses revealed a variety of cDNA-induced phenotypes providing broader insight into mesenchymal stem cell biology. |
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| 10:05 | Morning Networking & Coffee Break |
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| | FEATURED PRESENTATION |
| 10:45 | A Definable “Structure” for the Immune System and Cancers at the Single Cell Level |
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Garry Nolan
Professor
Department of Microbiology & Immunology
Stanford University |
| | It is insufficient to state that cancer is “heterogeneous” in nature. This is akin to stating the problem without suggesting a solution. We focus on the development of intracellular assays of signaling that correlate subsets of cells in complex populations with functional signaling and clinical states. Such correlations allow for documentation and ordering of the apparent heterogeneity in leukemias and other cancers into recognizable progressions. Using a next-generation single-cell “mass cytometry” platform we quantify surface and cytokine or drug responsive indices of kinase target with 45 or more parameter analysis (e.g. 45 antibodies, viability, nucleic acid content, and relative cell size). We have recently extended this parameterization to mRNA with the capability to measure down to 5 molecules per cell in combination with any other set of previously created markers.
I will present evidence of deep internal order in immune functionality which demonstrates that differentiation and immune activities have evolved with a definable “shape”. A hierarchy of functional trans-cellular modules is observable that can be used for mechanistic and clinical insights. I will focus upon AML and ovarian cancer in the presentation and demonstrate the apparent existence of reproducible ordering of cellular substates that define a limited boundary condition of “what is” a given cancer. |
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| 11:10 | Vascular Niche Technology for Stem Cell Expansion and Organ Regeneration |
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Organized by:
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GTCbio |
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Invited Speakers:
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| KEYNOTE SPEAKER | | Mark Mercola
Professor and Director, Muscle Development and Regeneration Program
Sanford-Burnham Medical Research Institute
Professor
University of California, San Diego | | FEATURED SPEAKER | | | | Geoffrey Bartholomeusz
Assistant Professor & Director of the siRNA Core Facility
University of Texas MD Anderson Cancer Center |  | Anthony Davies
Director, High Content Research Facility
National Center for High Content
Screening and Analysis (INCHA) |
| | Garry Nolan
Professor
Department of Microbiology & Immunology
Stanford University |
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| | DISTINGUISHED SPEAKERS | | | | Michelle Arkin
Associate Adjunct Professor, Biology
University of California, San Francisco | | Anne Bang
Director
Cell-Based Disease Modeling and Screening
Sanford-Burnham Medical Research Institute | | Benjamin Braun
Assistant Professor
Department of Pediatrics, Hemology/Oncology
University of California, San Francisco | | Bhavneet Bhinder
Computational Analyst
Memorial Sloan-Kettering Cancer Center | | Patrick Collins
Scientist
Amgen | | Robert Damoiseaux
Scientific Director
University of California, Los Angeles | | Hakim Djaballah
Director
High-Throughput Drug Screening Facility
Memorial Sloan-Kettering Cancer Center | | Helen Ho
Field Applications Scientist
IntelliCyt Corporation | | Thomas Hughes
Chief Scientific Officer
UMontana Molecular | | Dongeun Huh
Wilf Family Term Chair & Assistant Professor, Department of Bioengineering
University of Pennsylvania |
| | Bahram Jalali
Professor, Electrical Engineering Department
University of California, Los Angeles | | Kelvin Lam
Founder & President
Simplex Pharma Advisors | | Daniel LaBarbera
Assitant Professor, Pharmaceutical Sciences
University of Colorado School of Pharmacy | | Jan Lichtenberg
CEO & Co-Founder
InSphero AG | | Anjali Nath
Postdoctoral Fellow
Harvard Medical School/Massachusetts General Hospital |  | Daniel Nolan
Director of Research
Angiocrine Bioscience | | Haley Pugsley
Applications Scientist
Amnis | | Terry Riss
Senior Product Specialist, Cell Health
Promega Corporation | | Larry A. Sklar
Director
University of New Mexico
Center for Molecular Discovery | | Jennifer Smith
Assistant Director
ICCB-Longwood Screening Facility
Harvard Medical School |
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Deadline for Abstracts:
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October 8, 2013
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Registration:
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Please visit our website to register or write to customerservices@gtcbio.com.
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E-mail:
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customerservices@gtcbio.com
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