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Immediately preceding Cambridge Healthtech Institute's Pharmacogenomics Europe, May 23-24, 2001, Bayerischer Hof, Munich, Germany
Corporate Sponsors
Sponsoring Publications
Drug Discovery Today
Trends in Molecular Medicine
Pharmacogenomics
Trends in BiotechnologyGenomic information is being applied as a critical component of drug development strategies for identifying therapeutic targets and for mapping out pathways of genes and proteins to gain a comprehensive view of biology. This meeting will look into the technologies underlying proteomics, gene expression, and functional genomics as well as applying genomics to overall strategies in drug discovery. This promises to be a new information era in biology that will eventually allow the simultaneous detection and understanding of complex biological processes.
Scientific Advisors
Dr. Norman J.W. Russell, Lynx Therapeutics, Inc.
Dr. Michael K. Trower, GlaxoSmithKline Research and Development
Dr. Mathias Uhlén, Royal Institute of TechnologyAdditional Speakers
Dr. Peter Angel, German Cancer Research Center
Dr. John Ansell, John Ansell Consultancy
Dr. Christopher P. Ashton, Orchid BioSciences Europe Ltd.
Dr. Yvonne Boyd, Institute for Animal Health
Dr. Konrad Büssow, Max-Planck-Institute of Molecular Genetics
Dr. Gianfranco de Feo, Affymetrix Inc.
Dr. Mark Egerton, Incyte Genomics Ltd.
Mr. Jorge Goldstein, Sterne, Kessler, Goldstein and Fox, P.L.L.C.
Dr. Melvyn Hollis, Aventis Pharmaceuticals
Dr. Brent L. Kreider, Phylos, Inc.
Dr. Ulrich K. Laemmli, Geneva University
Dr. Pierre Legrain, Hybrigenics SA
Dr. Friedrich Lottspeich, TopLab
Dr. Alexander Olek, Epigenomics
Dr. Martin G. Reese, ValiGen
Dr. Fritz Rudert, Xerion Pharmaceuticals GmbH
Mr. Jean-Marie Sonet, Proteus
Dr. Johannes Streicher, University of Vienna
Dr. Gerald Walter, Biorchard AS
Dr. Edward D. Zanders, De Novo Pharmaceuticals Ltd.Mapping Protein Interactions
Reliable High-Throughput Protein Interaction Mapping
PROfusion: Genetically Tagged Proteins
The Challenge of Following Quantitative Protein Expression
Protein Arrays for Gene Expression and Molecular Interaction Screening
Functional Proteomics with Laser-Mediated Protein KnockoutFunctional Genomics
Functional Genomics in the Pharmaceutical Industry
High-Throughput Functional Genomics to Study Human Diseases
Phenomics-Based Biochips
Specific Gain-and-Loss-of-Function Phenotypes
Phenotype Map of the Mouse X Chromosome
Gene Identification and Annotation of Genomes for Drug Target Selection
Genetic Approaches to Identify FunctionsExpression Monitoring
High-Resolution Gene Expression Analysis Using Massively Parallel Signature Sequencing
Application of Gene Expression Monitoring
Human cDNA Library for Protein Expression Screening
3-D Visualization of Gene Expression Patterns and Related Morphological StructuresGenomic Drug Discovery
Keynote Presentation
Impact of Research Tool Patenting
Mr. Jorge Goldstein, Sterne, Kessler, Goldstein & Fox PLLC
The Impact of Genomics on Drug Discovery
How Genomic Technologies Will Be Used to Meet the Growing Needs of the Pharmaceutical Industry
Analyzing Genomics Deals
Launch of the Human Epigenome Consortium (HEC)
Ultrahigh-Throughput Genotyping Platform
Chemical Genomics: From Gene to Small Molecule
Sunday, May 20
5:00-7:00pm Early Registration
Monday, May 21
7:00am Registration, Poster and Exhibit Set-up, and Light Continental Breakfast
Mapping Protein Interactions
8:30 Chairperson's Opening Remarks
Dr. Pierre Legrain, Vice President, Science and Technology, Hybrigenics SA8:35 Reliable High-Throughput Protein Interaction Mapping for the Identification of Novel Pathways and Molecular Complexes
Dr. Pierre Legrain
Most diseases involve dysfunction of functional (signaling or metabolic) protein-related pathways at various levels, and the vast majority of therapeutic drugs are either targeting proteins or are proteins themselves. It is therefore key to integrate protein interactions into functional pathways in order to improve our understanding of pathological processes and to discover and validate new disease-related markers or novel therapeutics. Hybrigenics has developed, among other technologies, an innovative cDNA library approach of the Two Hybrid in Yeast, which allows reliable and high-throughput screening of protein-protein interactions. Resulting protein interaction maps are displayed through a user-friendly navigating and analysis bioinformatics interface—the PIMRider®.9:05 High-Throughput Protein Interaction Screens and Affinity Reagent Generation Using RNA-Protein Fusion Libraries
Dr. Brent L. Kreider, Vice President, Biological Research, Phylos, Inc.
In vitro RNA-protein fusion (PROfusion™) molecules provide an extremely powerful in vitro selection technology that has a broad range of applications including affinity reagent generation and protein interaction mapping. Multiple cellular libraries have been constructed and utilized for protein:protein, protein:drug and enzyme:substrate interaction mapping, yielding both known and novel interacting partners. We have also leveraged this technology for the selection of small, stable antibody mimics against a variety of targets. These high-affinity capture proteins have been used for the creation of a micro-ELISA type protein chip, providing an additional tool for proteomic applications. The further use of these reagents for functional knockout studies and conventional antibody type experiments provides a fully integrated platform for lead identification and target validation.9:35 Proteomics: The Challenge of Following Quantitative Protein Expression
Dr. Friedrich Lottspeich, Proteinanalytik, TopLab
Functional information in proteomics is obtained by the interpretation of the quantitative changes of proteins in different biological or clinical stages. However, sample preparation, protein separation, and protein detection all have a major impact on the quantitative results. State of the art, limitations, and future aspects in obtaining reliable and comprehensive quantitative protein patterns will be discussed.10:05 Poster and Exhibit Viewing, Refreshment Break
11:00 Protein Arrays for Gene Expression and Molecular Interaction Screening
Dr. Gerald Walter, Biorchard AS
Protein arrays appear as new and versatile tools in functional genomics, enabling the translation of gene expression patterns of normal and diseased tissues into protein product catalogues. Protein function such as enzyme activity, antibody specificity, or other ligand-receptor interactions and binding of nucleic acids or small molecules can be analyzed on a whole-genome level. The emerging future array systems will be used for high-throughput functional annotation of gene products, their involvement in molecular pathways, and their response to medical treatment, and will become the doctor's indispensable diagnostic tools.11:30 Functional Proteomics with Laser-Mediated Protein Knockout
Dr. Fritz Rudert, Director of Functional Biology, Xerion Pharmaceuticals GmbH
After completion of the human genome sequence, the next "big thing" of the post-genomics era will be to assign function to genes and to validate them as therapeutic drug targets. Chromophore-assisted laser inactivation (CALI) can specifically inactivate protein function in cell-free and cell-based assays by targeted induction of photochemical modifications. Automated CALI, combined with target-specific scFv antibodies selected by phage display, constitutes a high-throughput protein knockout platform, XCALIbur™. This approach can provide rapid information about protein function in cellular and disease-relevant pathways.12:00 Panel Discussion
12:30 Luncheon (Sponsored by Cambridge Healthtech Institute)
Functional Genomics
13:45 Chairperson's Remarks
Dr. Mathias Uhlén, Professor, Department of Biotechnology, Royal Institute of Technology13:50 Pharmaceutical Genomics: Functional Genomics in the Pharmaceutical Industry
Dr. Melvyn Hollis, Head, Functional Genomics, Aventis Pharmaceuticals
A brief overview of the application of a diverse set of genomics and functional genomics techniques to the discovery and development of pharmaceuticals will be presented. Particular emphasis will be placed on the application of high-throughput methodologies for target identification and validation. Examples of the application and integration of some of these techniques within the Aventis Drug Innovation and Approval organization will be presented.14:20 High-Throughput Functional Genomics to Study Human Diseases
Dr. Mathias Uhlén
High-throughput systems for analysis of genetic variability (SNP), transcript profiling, and affinity-reagent based proteomics have been set up based on "in-house" designed robotic workstations (Ronaghi, Uhlén and Nyren, Science 281, 363-365, 1998). The analysis of transcript profiling is based on a visualization tool (Larsson et al., Genomics 63, 341-353, 2000) allowing comparative studies of experimental data from many different platforms, including oligonucleotide- and cDNA-arrays as well as high-throughput signature sequencing, including SAGE and Pyrosequencing. The proteomics approach is based on high-throughput expression of cDNAs or exons predicted from genomic data, and the generation of affinity reagents is based on affibodies (Nord et al., Nature Biotechnology 15, 772-777, 1997). The high-throughput analysis methods have been used for pharmacogenetic analysis of patients treated for various diseases, including cancer and cardiovascular disorders.14:50 Phenomics-Based Biochips
Mr. Jean-Marie Sonet, Director of Marketing, Proteus
PHENOMICS® allows rapid access to the entire expressed proteome from a given genome. Under the proprietary PHENOMICS® process, each protein is functional and sorted so that immediate access to the corresponding genetic information is maintained. Proteus and CEA-LETI (Instrumentation, Technology and Electronics Laboratory of the Atomic Energy Commission) have joined their efforts to miniaturize the current microtiter plate format of the technology into PHENOMICS® biochips. The combination of the know-how and patented technologies of both CEA-LETI and Proteus is targeting the development of novel tools for high-throughput functional analysis of the genome that the industry is demanding in this post-genomic era.15:20 Specific Gain-and-Loss-of-Function Phenotypes Induced by Satellite-Specific DNA Binding Drugs Fed to Drosophila Melanogaster
Dr. Ulrich K. Laemmli, Departments of Biochemistry and Molecular Biology, Geneva University
Experimental tools to dissect and elucidate the functions of DNA satellites and other nongenic DNA are largely missing. To overcome this lack, we explored the experimental potential of DNA sequence-specific drugs containing pyrrole and imidazole amino acids (polyamides). Compounds were synthesized that target different Drosophila melanogaster satellites. Dimeric oligopyrroles were shown to target the AT-rich satellites I, III, and SARs (scaffold associated regions). One polyamide (P31) specifically binds the GAGAA satellite V and another (P9) targets the AT-rich satellites I and III. Specificity of targeting was established by footprinting, epifluorescence of nuclei, and polytene chromosomes stained with fluorescent derivatives. Remarkably, these drugs, when fed to developing Drosophila flies, caused gain-or-loss-of-function phenotypes. While polyamide P9 (not P31) suppressed PEV of white-mottled flies (increased gene expression), P31 (not P9) mediated three well-defined, homeotic transformations (loss-of-function) exclusively in brown-dominant flies. Both phenomena are explained at the molecular level by chromatin opening (increased accessibility) of the targeted DNA satellites. Chromatin opening of satellite III by P9 is proposed to suppress PEV of white-mottled flies whereas chromatin opening of satellite V by P31 is proposed to create an inopportune "sink" for the GAGA factor (GAF).15:50 Poster and Exhibit Viewing, Refreshment Break
16:30 A Phenotype Map of the Mouse X Chromosome
Dr. Yvonne Boyd, Institute for Animal Health
Since there are considerable phenotypic similarities between human and mouse genetic disorders, mouse mutants provide animal models for understanding disease pathogenesis and for assessing therapeutic regimes as well as means of investigating gene function. The size of the mouse mutant resource is being greatly enhanced by the products of several large mouse mutagenesis programs. The first stages in the classification of all mutants, which will be illustrated using the paradigm of X-linked genetic disorders, involve phenotypic characterization and mapping. The phenotype maps produced by this classical approach complement those being generated from targeted gene knockouts.17:00 Gene Identification and Annotation of Genomes for Drug Target Selection
Dr. Martin G. Reese, Director of Informatics Discovery, ValiGen
The DNA sequence of the euchromatic portion of various genomes has been determined to very high accuracy and completion. An initial analysis and preliminary gene annotation and interpretation have been performed. I will demonstrate on the genome of Drosophila melanogaster an approach for complete genome annotation focusing on gene identification. The specific aim is to show the importance of genome annotation for the identification and functional classification for drug target selection.17:30 Genetic Approaches to Identify Functions of Transcription Factor AP-1 (Fos/Jun) Target Genes in Cell Growth and Differentiation
Dr. Peter Angel, Head of Division, Deutsches Krebsforschungszentrum (DKFZ), German Cancer Research Center
Transcription factor AP-1 (Fos/Jun) mediates gene regulation in response to many extracellular stimuli including, growth factors, cytokines, oncoproteins, and genotoxic agents. Loss-of-function approaches in mice led to the identification of specific, non-overlapping functions of AP-1 subunits. For example, c-Jun and JunB play an essential role in hepatogenesis and heart development, and angiogenesis and placentation, respectively. Fibroblasts derived from c-jun-/- and junB-/- mouse fetuses exhibit severe defects in apoptosis in response to genotoxic agents and cell proliferation. In addition to the cell-autonomous regulatory function in cell proliferation, using an in vitro tissue-engineered skin equivalent model c-Jun and JunB proteins were found to antagonistically affect the expression of diffusible, fibroblast-derived factors, such as KGF and GM-CSF, acting in a paracrine way on keratinocytes cell proliferation and differentiation. The in vitro skin model using genetically defined mutant fibroblasts represents a powerful system to study functional complementation of deficiencies in order to identify critical cytokines such as KGF and GM-CSF and to define their specific activity to promote keratinocyte proliferation, differentiation, or both. Moreover, it may serve as the basis for the dissection of disease mechanisms and identification of the molecular mechanism of dermal-epidermal interactions in skin physiology and pathology. Finally, I will describe an in vitro differentiation system using wild-type mouse embryonic stem cells that allows the identification of JunB target genes, which are critically involved in the process of angiogenesis.18:00 Panel Discussion
18:30 End of Day One
19:00
All Participants of the Impact of Genomics on Medicine conference are cordially invited to be guests at the State of Bavaria Reception and Buffet Dinner at the "Residence" (Kaisersaal) Munich to be hosted by State Minister Dr. Otto Wiesheu, Bavarian Ministry for Economic Affairs,Transport and Technology
Tuesday, May 22
8:00am Poster and Exhibit Viewing and Light Continental Breakfast
Expression Monitoring
8:30 Chairperson's Remarks
Dr. Norman J.W. Russell, President and Chief Executive Officer, Lynx Therapeutics, Inc.8:35 High-Resolution Gene Expression Analysis Using Massively Parallel Signature Sequencing (MPSS)
Dr. Norman J.W. Russell
Modern biology requires a further step in the evolution of DNA analysis, such that millions of DNA molecules can be handled and analyzed simultaneously. Lynx's Megaclone Technology is a unique and proprietary procedure for constructing libraries of cloned DNA fragments on microbeads, and one application of this technology is Massively Parallel Signature Sequencing (MPSS). MPSS enables high-resolution gene expression profiling and obtains sequence information from millions of cDNAs simultaneously. These comprehensive data identify even the rarest transcripts, and examples will be presented to illustrate the advantages of this depth of analysis.9:05 Application of Gene Expression Monitoring
Dr. Gianfranco de Feo, Program Manager, Genomic Collaborations, Affymetrix Inc.
Using GeneChip microarrays for gene expression studies allows researchers to analyze all known expressed genes simultaneously. The technology used to generate GeneChip arrays, as well as software and web tools that allow researchers to understand the data generated from the arrays, will be briefly reviewed. Published and unpublished studies demonstrating the benefits of massively parallel gene expression analysis to studying disease mechanisms and treatment will also be discussed.9:35 Poster and Exhibit Viewing, Refreshment Break
10:15 Human cDNA Library for High-Throughput Protein Expression Screening
Dr. Konrad Büssow, Max-Planck-Institute of Molecular Genetics
The Protein Structure Factory (PSF, http://www.fu-berlin.de/psf) is an initiative of research institutes and companies in the Berlin area covering the fields of protein structure analysis, biophysics, genomics, protein expression, and bioinformatics. It was established to characterize the structures of proteins encoded by the large number of human genes being discovered, using automation technology to accelerate the process from the protein sequence to the structure. Proteins are selected for structure analysis that have an unknown structure, do not contain nonglobular domains, and for which full-length cDNA clones are available. In addition to whole proteins, there is a focus on predicted single domains. In the E. coli expression project of the Protein Structure Factory at the Max-Planck-Institute of Molecular Genetics, human cDNA sequences are subcloned into expression vectors for overexpression in E. coli. A parallel project for expression in yeasts has been established for proteins that are difficult to express using bacterial systems. Subcloning is performed by standard techniques, which are adapted to the microtiter plate format to increase the throughput. PCR products purification and bacterial colony picking are performed by robotic systems. Human cDNA clones as templates for subcloning are obtained either from the Berlin Resource Center of the German Human Genome Project (RZPD, http://www.rzpd.de/) or from expression libraries developed at the Max-Planck-Institute. These libraries are arrayed in microtiter plates and onto high-density colony filters using robot technology. Screening of high-density protein arrays, protein expression, and purification in microtiter plates, SDS-PAGE, and mass spectrometry identify clones that express human proteins with the desired properties.10:45 3-D Visualization of Gene Expression Patterns and Related Morphological Structures
Dr. Johannes Streicher, Department of Anatomy, University of Vienna
A major prerequisite for understanding gene function under regular and experimental conditions in morphogenetic, dysmorphogenetic, and pathophysiological processes is the accurate spatio-temporal correlation of the expression patterns with related morphological structures. We will present a highly automated, objective, and time-saving method for combined 3-D visualization of gene expression patterns and morphological structures. The resulting 3-D models of each aspect (gene expression and morphology) can be viewed simultaneously, in any combination and from any point of view, thereby revealing new aspects of gene expression topography that cannot be seen by conventional visualization methods such as whole-mount or single-section in situ. Documentation is possible in all formats ranging from single images through stereoscopic views and movies up to virtual reality scenes that can be as well published in universally accessible digital formats in www-databases.11:15 Application of Genomics in Biomedical Research
Dr. Mark Egerton, Vice President, European Business Operations, Incyte Genomics Ltd.
What is the genome? Utilizing and extracting the maximum value from the Incyte full-length gene identification and reagent generation program will be discussed. The technology platforms for generating higher value genomic content, challenges of managing the vast amount of genomic information, and future impact of genomics in biomedical research will also be covered.11:45 Luncheon (Sponsored by Cambridge Healthtech Institute)
Genomic Drug Discovery
13:00 Chairperson's Remarks
Dr Michael K. Trower, Pathway Genomics, Genetics Research, GlaxoSmithKline Research and DevelopmentKeynote Presentation
13:05 Impact of Research Tool Patenting
Mr. Jorge Goldstein, Director, Sterne, Kessler, Goldstein and Fox, P.L.L.C.
Many patents containing claims on drug discovery tools have been issued or are pending, including (1) cDNA fragments; (2) crystallized receptors, especially in software related patents; and (3) target genes/proteins and their uses in screening and in mechanistic therapeutic applications. We will discuss the US PTO's views on the utility of such claims and their potential court interpretation, and we will especially emphasize reach-through issues, claim scope, and litigation damages.13:45 The Impact of Genomics on Drug Discovery
Dr. Michael K. Trower
Summary unavailable at time of printing.14:15 Analyzing Genomics Deals
Dr. John Ansell, John Ansell Consultancy
This presentation will focus on (1) what the database can and can't do, (2) the geographics of partnering, (3) trends in types of genomics technologies, (4) selected genomics company activity, and (5) selected major pharmaceutical company activity.14:45 Poster and Exhibit Viewing, Refreshment Break
15:30 From Genomics to Epigenomics: Launch of the Human Epigenome Consortium (HEC)
Dr. Alexander Olek, Epigenomics
Epigenomics has developed the technology to uncover an entirely new layer of biological information; by detecting and interpreting DNA's 5th base through its methylation patterns (5th BASE genomics®), we are cementing the cornerstones for personalized medicines. These DNA methylation signals, comparable to a switch turning on or off individual genes, can be digitized to create a unique fingerprint for each cell (Digital Phenotype®). The Human Epigenome Consortium was formed between the Sanger Center, Cambridge, U.K.; the Centre National de Génotypage, Paris, France; and Epigenomics AG, Berlin, Germany. Its aim is to detect all methylation positions of the human genome and to make these data publicly available.16:00 The MegaSNPatron: An Ultrahigh-Throughput Genotyping Platform
Dr. Christopher P. Ashton, Vice President and Managing Director of European Operations, Orchid BioSciences Europe Ltd.
The availability of the completed human genome and the discovery of potentially 1,000,000 SNPs or more by the end of 2000 have fueled the demands for rapid, low-cost, and flexible methods for single nucleotide polymorphism (SNP) genotyping. There is an emerging opportunity to understand how drug response, adverse drug effects, and genetic predisposition to disease of individual patients can be correlated to specific SNPs on a genomewide scale. Finding these correlations requires that an ever-increasing number of SNPs be analyzed against a very large number of patient samples and has driven a requirement toward vast genotyping capacity, at least a million SNP samples per day, in order to make these key pharmacogenetic correlations. Orchid has been a leader in high-throughput genotyping with its SNPstream 25K, a robotic platform performing Orchid's SNP-IT™ primer extension biochemistry. The next-generation product, internally referred to as the "MegaSNPatron," is designed as a series of modules, each capable of routine, 100K, SNP/day operation with the ability to perform at higher throughputs. To achieve the ultrahigh throughputs of the MegaSNPatron, the core primer extension genotyping biochemistry, SNP-IT™, has been adapted to a novel fluidics platform device that draws from the inherent scalability and automatability of the standard microtiter plate format. Direct fluorescence read-out in a novel array-reading detection system and PCR and genotyping multiplexing support in an array-based platform maintain the processing flexibility features of the SNPstream system while enabling significant per analysis reagent reduction. Results on the performance of the MegaSNPatron system for a range of different SNPs will be presented.16:30 Chemical Genomics: From Gene to Small Molecule
Dr. Edward D. Zanders, Vice President, Discovery Genomics, De Novo Pharmaceuticals Ltd.
The primary value of genomics to the pharmaceutical industry lies in the creation of small molecule drugs from information encoded in the genome. The linear process of gene selection, protein isolation, and structure determination can only be completed with the identification of compounds with suitable binding properties. Given the thousands of possible targets, there is a clear need for efficient molecular design technologies to provide suitable candidates for synthesis and testing. The aim is to be able to identify compounds that bind selectively to the target of choice, either for further development into drug candidates or for use as probes into basic biological processes in health and disease. The rapid improvement in small molecule design processes means that "chemical genomics" is becoming a realistic approach to drug discovery.17:00 Panel Discussion
17:30 Close of Conference
Corporate Sponsor Biographies
Amersham Pharmacia Biotech(APBiotech), the life sciences business of Nycomed Amersham plc, is a leading provider of biotechnology systems, products and services for research into genes and proteins, for the discovery and development of drugs and for the manufacture of biopharmaceuticals. The customers for APBiotech's products and technology are pharmaceutical and biotechnology companies and leading research and academic institutions in North America, Europe, Latin America and Asia. For more information about APBiotech, please visit our web site at www.apbiotech.com
Incyte Genomics Inc. is a leading provider of an integrated platform of genomic technologies designed to aid in the understanding of the molecular basis of disease. Incyte develops and markets genomic databases, genomic data management software, microarray-based gene expression services, related reagents and services. These products and services assist pharmaceutical, biotechnology and academic researchers with all phases of drug discovery and development, including gene discovery, understanding disease pathways, identifying new disease targets and the discovery and correlation of gene sequence variation to disease.
Hotel Information
Hotel Bayerischer Hof
Promenadeplatz 2-6
80333 Munich
Germany
T: 49-89-21-20-0
F : 49-89-21-20-906
Cut-off Date: April 6, 2001Travel Information
Special Airline Discounts Available
You may call Great International and National Travel at 617-527-0800 and ask for Joyce Dunn or e-mail her at jdunn@greatintltravel.com.Poster Information
Cambridge Healthtech Institute encourages attendees to gain further exposure by presenting their work in the poster sessions. Please fill out the registration form, with the poster title and primary author. To ensure inclusion in the conference binder, a one-page summary must be submitted and registration must be paid in full by April 13, 2001. POSTER INSTRUCTIONSExhibit Information
Exhibit space is available for companies interested in exhibiting equipment, instruments, reagents, software, information, or other products and services. Last year's meeting attracted highly targeted researchers and executives representing a large number of the leading commercial, academic, and government organizations active in Proteomics, Gene Expression, Functional Genomics, and related activity. Please contact Jim MacNeil of Cambridge Healthtech Institute at 617-630-1341 to obtain an exhibitor package or to inquire about offering a workshop during the meeting. Exhibit space is limited so call now to reserve a space at this event.
Phone: 617-630-1300, Fax:
617-630-1325
Email: chi@healthtech.com
