Institutes
Institute for Translational Biomedical Sciences
The Institute for Translational Biomedical Sciences (ITBS) is home to basic research on human disease that is seamlessly integrated with translational research to identify potential new therapeutic and diagnostic medicines. Leveraging the CIIT 30 year history of excellence in public health and environmental sciences research the ITBS shares a common platform with CIIT in health outcomes based systems biology.
The ITBS is anchored by the Center for Molecular Safety Sciences.
Center for Molecular Safety Sciences
Current testing methods and risk assessment have not kept pace with the rapid evolution of technology, biomedical research and knowledge generation. For example, the battery of studies required to meet regulatory guidelines for development and approval of pharmaceuticals, rely almost exclusively on in vivo animal testing protocols and endpoint assessments which have changed very little in decades. These current methods are not completely reliable in their ability to predict complex and low incidence effects in humans and do not always lead to the mechanistic insight of the causes or biology of adverse events. As astutely described in a recent study published by the National Research Council, "Toxicity testing is approaching a scientific pivot point. It is poised to take advantage of the revolutions in biology and biotechnology. Advances in toxicogenomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform toxicity testing from a system based on whole animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferably of human origin."
Regulatory agencies have also recognized the need for process improvements in the Development and Safety Sciences and to meet these challenges are fostering consortia and collaborations with industry, academia and regulatory agencies.
The Center for Molecular Safety Sciences (CMSS) is a strategic collaboration between The Hamner Institutes for Health Sciences, Duke University and the University of North Carolina. Functioning as a neutral fourth party, the CMSS will catalyze the responses of industry, academics and regulatory agencies to the FDA's Critical Path Initiative and Europe's Innovative Medicines Initiative.
The CMSS will create a leading position in characterizing the inherent risks of pharmaceuticals and markedly improve drug development and post marketing processes in close collaboration with the FDA and other regulatory agencies. The science and methods will be centered in Systems Biology and Translational Research enabling the observations and outcomes of laboratory investigations to be readily validated using in vivo models and rapidly assessed in humans.
In a sense, contemporary systems biology is a renaissance of physiology, a traditional integrative discipline. Biological research has enjoyed decades of success in dissecting the structures and functions of individual molecular and cellular components comprising an organism. However, the inherent complexity of biological systems, due not only to the large number of their constituents, but also to the intricate web of interactions between these constituents, have proven difficult to understand with reductionist approaches. Research has to be conducted at a more global, systems-level in order to gain understanding of the overall behavior of the biological networks that maintain normal physiology and the perturbations in these networks that lead to toxicity and disease. Environmental stressors, including physical and chemical agents, exert adverse effects by initially impinging on specific molecular or cellular targets. The ensuing responses triggered from the initial interactions and subsequently propagated along the normal molecular, cellular or systemic networks, will ultimately affect the health of the intact organism. Our applications of computational systems biology in risk assessment focuses on developing quantitative simulation models of the dose-response relationships for network perturbations by chemical stressors and drugs.
The value of an integrated and systematic approach to the study of the biology of complex pathopysiologic processes that is enabled by Systems Biology approaches is depicted in Figure 2. Using modern "omics" technologies, knowledge generation and intelligent networking tools and targeted modeling methods, the pathophysiology of a well-known, but enigmatic phenomenon of chemically induced vascular injury has been elucidated. Not only was the application of a Systems Biology approach essential to the characterization of the signals and pathways of these events, but long sought after leading biomarkers were also identified. This research endeavor generated over one million data points that were also rigorously reviewed and analyzed by the FDA and they too, reached essentially the same conclusions. Importantly, the leading biomarkers identified by these studies are now being validated in human experiments and may lead to the renewed development of a very important class of potential therapeutics.
A key and unique attribute of the CMSS capability is the broadened and integrated focus on Translational Research: the ability to take the Systems Biology, i.e., non-human derived information, and seamlessly validate the key concepts in humans is essential to the overall success of the CMSS enterprise. The partnerships and shared faculty with the University of North Carolina Schools of Pharmacy and Medicine and the Duke University School of Medicine's Genomic Medicine Department will ensure the unprecedented ability to efficiently and effectively move key learnings and observations from the laboratory bench through in vivo nonhuman confirmations directly to human assessment and validation.