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The Continuing Challenges of Translational Research: Clinician-Scientists’ Perspective  [PDF]
Shervanthi Homer-Vanniasinkam,Janice Tsui
Cardiology Research and Practice , 2012, DOI: 10.1155/2012/246710
Abstract: Over the last twenty years, revolutionary advances in biomedicine including gene therapy, stem cell research, proteomics, genomics and nanotechnology have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. Over the past ten years, funding bodies in the USA and UK such as the National Institutes of Health (NIH) and the Medical Research Council (MRC) have been driving translational research by defining and tackling the hurdles but more still remains to be achieved. This article discusses the ongoing challenges translational researchers face and outlines recent initiatives to tackle these including the new changes to translational funding schemes proposed by the NIH and the MRC and the launch of the “European Advanced Translational Research InfraStructure in Medicine” (EATRIS). It is anticipated that initiatives such as these will not only strengthen translational biomedical research programmes already initiated but should lead to rapid benefits to patients and society. 1. Introduction Translational research (TR) is a relatively new area of investigation that ideally involves the integrated application of innovative technologies that encompass multiple disciplines including physiology, pathophysiology, natural history of disease, genetics, and proof-of-concept studies of drugs and devices [1]. TR describes a continuum of research in which basic science discoveries are utilized to prevent or treat human disease. It is an iterative process wherein scientific discoveries are integrated into clinical applications and, conversely, clinical observations are used to generate research foci for basic science: the “bench to bedside and back to bench” approach. Initially, 2 phases in TR were described: T1. basic science discoveries used to develop new treatments for disease (“bench to bedside”), T2. research aimed at improving utilization of proven therapies in clinical practice and community settings (“bedside to community”). More recently, this has been redefined to include 3 phases in TR, with the second phase being subdivided. Thus, in this new model T1 describes basic science to clinical science, T2 clinical science to clinical practice, and T3 is used to denote the translation of clinical practice to more widespread health improvements [2]. Whilst the importance and benefits of TR are now clear to most, significant challenges faced by investigators have also been recognised. This
Translational Research  [cached]
Stephen M. Fleming
Opticon1826 , 2009, DOI: 10.5334/opt.060910
Abstract: A cursory glance through recent issues of the leading science journals that are found lying on your average university coffee table (Nature, Science, PNAS) will be enough to convince you that UCL Life Sciences are thriving. With alumni as illustrious as the molecular biologist Francis Crick and evolutionary theorist John Maynard Smith, this shouldn’t come as too much of a surprise. But now UCL is also leading the way with so-called ‘translational’ research – medical science that seamlessly strides into the public domain, with the potential to directly impact on people’s lives. Think penicillin, anti-depressants and polio vaccinations, and you’re on the right lines.
The cancer translational research informatics platform
Patrick McConnell, Rajesh C Dash, Ram Chilukuri, Ricardo Pietrobon, Kimberly Johnson, Robert Annechiarico, A Jamie Cuticchia
BMC Medical Informatics and Decision Making , 2008, DOI: 10.1186/1472-6947-8-60
Abstract: caTRIP has been developed as an N-tier architecture, with three primary tiers: domain services, the distributed query engine, and the graphical user interface, primarily making use of the caGrid infrastructure to ensure compatibility with other tools currently developed by caBIG. The application interface was designed so that users can construct queries using either the Simple Interface via drop-down menus or the Advanced Interface for more sophisticated searching strategies to using drag-and-drop. Furthermore, the application addresses the security concerns of authentication, authorization, and delegation, as well as an automated honest broker service for deidentifying data.Currently being deployed at Duke University and a few other centers, we expect that caTRIP will make a significant contribution to further the development of translational research through the facilitation of its data exchange and storage processes.In order to have an impact in society, discoveries in cancer research need to be translated into knowledge that can be directly applied to treatment and prevention. These discoveries usually start within the basic sciences, from experiments developed at the molecular level, slowly progressing to clinical research. Although this translational process is at the very basis of our ability to generate new biomedical knowledge, to date few tools have been developed to successfully link the basic and clinical science fields in a way that researchers from both arenas can easily make connections. More specifically, cancer research would benefit from the development of applications that can aggregate clinical and molecular data in a repository that is user-friendly, easily accessible, as well as compliant with regulatory requirements of privacy and security.In alignment with the requirements outlined above, the Duke Comprehensive Cancer Center (DCCC), in collaboration with SemanticBits LLC, has developed the Cancer Translational Research Informatics Platform (c
Institutional shared resources and translational cancer research
Paolo De Paoli
Journal of Translational Medicine , 2009, DOI: 10.1186/1479-5876-7-54
Abstract: In fact, the physical build-up of SRs per se is not sufficient for the successful translation of biomedical research. Appropriate policies to improve the academic culture in collaboration, the availability of educational programs for translational investigators, the existence of administrative facilitations for translational research and an efficient organization supporting clinical trial recruitment and management represent essential tools, providing solutions to overcome existing barriers in the development of translational research in biomedical research centers.In the last few years there has been a tremendous expansion in translational research studies requiring integrated multidisciplinary efforts or special expertise that are not widely available to individual researchers. In fact, single laboratories, clinical divisions, or research groups do not possess sufficient financial funding, space or well-trained personnel to afford such opportunities. Therefore, the development and maintenance of adequate shared infrastructures is considered a major goal for academic centers promoting translational research programs [1,2]. Among infrastructures favoring translational research, centralized facilities characterized by shared, multidisciplinary use (by different departments, Divisions, Research Units) of expensive laboratory instrumentation, or by complex computer hardware and software and/or by high professional skills are necessary to maintain or improve institutional scientific competitiveness. This article may be particularly interesting for the scientific community since it includes the novel, exhaustive analysis of the shared resources necessary to support research activities in a comprehensive cancer center. Aims and advantages of establishing efficient shared resources for research centers and for investigators can be summarized as follows [3,4]:- Institutional, rather than individual, investments offer the opportunity to buy the most technically advanced, hig
Translational research in retinology  [cached]
Siqueira RC,Jorge R
Clinical Ophthalmology , 2011,
Abstract: Rubens Camargo Siqueira1,2, Rodrigo Jorge21Rubens Siqueira Research Center, S o José do Rio Preto, S o Paulo, Brazil; 2Retina and Vitreous Section, Department of Ophthalmology, School of Medicine of Ribeir o Preto, University of S o Paulo, BrazilAbstract: Clinical laboratories are strong, integral partners in personalized health care. Laboratory databases hold a vast amount of data on human phenotypes, genotypes, biomarkers, progression of disease, and response to therapy. These structured and unstructured free text data are critical for patient care and a resource for personalized medicine and translational research. Laboratory data are integrated into many electronic medical records that provide “summary reports” and “trending” to visualize longitudinal patient data. Recent advances in ophthalmology such as gene therapy, cell therapy using stem cells, and also retinal prosthesis explore the potential of translational research marking a new era in research into the diagnosis and treatment of eye diseases.Keywords: translational, retinal diseases, stem cell, gene therapy
Conflicts of interest in translational research
Malcolm R Parks, Mary L Disis
Journal of Translational Medicine , 2004, DOI: 10.1186/1479-5876-2-28
Abstract: By its nature, translational research crosses boundaries between basic science and clinical application. It places researchers in new contexts and ushers in a range of new contacts and relationships. Crossing these boundaries contributes directly to the creativity and social impact of translational medicine. But crossing these boundaries also gives rise to new and often conflicting obligations between researchers, their employers, and their industry sponsors. The public is rightfully concerned that the financial interests of researchers, their institutions, and their corporate sponsors may bias research. Yet history also teaches us that industry collaboration is often essential in realizing the promise of translational research. Industry collaboration has figured prominently in many translational research successes including recombinant growth hormone, angioplasty, stenting for coronary artery disease, and many new medications and diagnostic devices [1].Translational researchers must, therefore, understand what financial conflicts of interest are and how they are managed. Their industry partners must understand the constraints placed on researchers by federal and university policies as well as state laws. Relevant policies in the United States include the regulations issued by the Public Health Service and published as part of the Code of Federal Regulations (42 CFR 50.601–50.607) and in the National Science Foundation Grant Policy Guide (Section 510) [2,3]. Laws governing the use of state-owned resources may also be relevant for those working at or with public universities.Conflicts may arise whenever researchers' outside, personal financial interests have the potential to compromise an investigator's professional judgment and independence in the design, conduct, or publication of research. The most commonly regulated financial interests include consulting fees or compensation for personal services, equity or other ownership interests, royalties, and intellectual p
Translational research in retinology
Siqueira RC, Jorge R
Clinical Ophthalmology , 2011, DOI: http://dx.doi.org/10.2147/OPTH.S25249
Abstract: anslational research in retinology Review (2473) Total Article Views Authors: Siqueira RC, Jorge R Published Date October 2011 Volume 2011:5 Pages 1493 - 1498 DOI: http://dx.doi.org/10.2147/OPTH.S25249 Rubens Camargo Siqueira1,2, Rodrigo Jorge2 1Rubens Siqueira Research Center, S o José do Rio Preto, S o Paulo, Brazil; 2Retina and Vitreous Section, Department of Ophthalmology, School of Medicine of Ribeir o Preto, University of S o Paulo, Brazil Abstract: Clinical laboratories are strong, integral partners in personalized health care. Laboratory databases hold a vast amount of data on human phenotypes, genotypes, biomarkers, progression of disease, and response to therapy. These structured and unstructured free text data are critical for patient care and a resource for personalized medicine and translational research. Laboratory data are integrated into many electronic medical records that provide “summary reports” and “trending” to visualize longitudinal patient data. Recent advances in ophthalmology such as gene therapy, cell therapy using stem cells, and also retinal prosthesis explore the potential of translational research marking a new era in research into the diagnosis and treatment of eye diseases.
Planning for translational research in genomics
Naomi Hawkins, Jantina de Vries, Paula Boddington, Jane Kaye, Catherine Heeney
Genome Medicine , 2009, DOI: 10.1186/gm87
Abstract: The translation of research findings into clinical practice is an important aspect of medical progress. Even for the early stages of genomics research, which aims to deepen our understanding of underlying mechanisms of disease, questions about the ways in which such research ultimately can be useful in medical treatment and public health are of key importance. The aim of this paper is to put forward concrete ways to enhance the process of translation by focusing on the key considerations that need to be taken into account in the early planning stages of a research project when the translation of research findings into clinical use may seem quite remote. Whilst some research data may not apparently lend themselves to an immediate clinical benefit, being aware of the issues surrounding translation at an early stage can enhance the delivery of the research to the clinic if a medical application is later found. When simple steps are taken during initial project planning, the pathways towards the translation of genomic research findings can be managed to optimize long-term benefits to health. This paper discusses the key areas of collaboration agreements, distribution of revenues, and recruitment and sample collection that are increasingly important to successful translational research in genomics. Such consideration is timely in light of the recent report on Genomic Medicine by the House of Lords in the UK, which recognized translation as vital to realizing the potential of genomic medicine, and the need to address various obstacles to successful translation [1].A significant proportion of genomics research is still at a very early stage in terms of clinical outcomes. Despite early excitement about the results of genome-wide association studies, recent debates in the scientific literature highlight that most of the variants found through this methodology account for only a small degree of the relative risk of developing a disease or a trait, and the findings collectivel
Advanced therapies for the treatment of hemophilia: future perspectives  [cached]
Liras Antonio,Segovia Cristina,Gabán Aline S
Orphanet Journal of Rare Diseases , 2012, DOI: 10.1186/1750-1172-7-97
Abstract: Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression.
Collaborative software for traditional and translational research
Berman Ari E,Barnett William K,Mooney Sean D
Human Genomics , 2012, DOI: 10.1186/1479-7364-6-21
Abstract: Biomedical research has entered a period of renewed vigor with the introduction and rapid development of genomic technologies and next-generation sequencing methods. This research paradigm produces extremely large datasets that are both difficult to store and challenging to mine for relevant data. Additionally, the thorough exploration of such datasets requires more resources, personnel, and multidisciplinary expertise to properly analyze and interpret the data. As a result, modern biomedical research practices are increasingly designed to include multi-laboratory collaborations that effectively distribute the scientific workload and expand the pool of expertise within a project. The scope of biomedical research is further complicated by increased efforts in translational research, which mandates the translation of basic laboratory research results into the human medical application space, adding to the complexity of potential collaborations. This increase in multidisciplinary, multi-laboratory, and biomedical translational research identifies a specific need for formalized collaboration practices and software applications that support such efforts. Here, we describe formal technological requirements for such efforts and we review several software solutions that can effectively improve the organization, communication, and formalization of collaborations in biomedical research today.
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