The most important challenge in health research is the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public — from diagnostics and therapeutics to medical procedures and behavioural changes. Translational Science is the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process.

The implementation of our strategic plan is guided by a broad and inclusive description of translational medicine to reflect the diversity of scientific disciplines involved in translational research within our Society. For our department, translational research, translational science and translational medicine are used interchangeably with a unifying principle that the ultimate purpose is to improve human health via a “bench to bedside” approach. The Institute for Scientific Research has taken leading part into research-oriented, patient-oriented clinical treatments, in collaboration with designated to the patients medical teams.

Overview

Translational Medicine is a multi-faceted discipline, bridging across the discovery, development, regulation, and utilisation spectrum. It may include application of research findings from genes, proteins, cells, tissues, organs, and animals, to clinical research in patient populations, all aimed at optimising and predicting outcomes in specific patients. Developing treatments that take individual variability into account (“personalized medicine”) has given rise to this new discipline in science. Scientists in this field work to translate biological phenomena into targeted, evidence-based medicines that improve health and treat disease by more optimally matching drugs and individuals. Currently, at least 95 percent of pharmaceutical companies are performing translational research and the translational efforts are driving many of the new therapies entering the clinic today. For clinical pharmacology, the focus of translational research is on the discovery, development, regulation and use of pharmacologic agents to improve clinical outcome, and inform optimal use of therapeutics in patients. In addition, translational research in clinical pharmacology may include evaluation of various biomarkers of pharmacologic response and assessing the linkage between biomarker response and clinical endpoints in patients. Our broad description also includes how the response to a therapeutic intervention in a particular disease may translate to a response in another disease, as well as translation of safety signals across species and/or patient populations. Translational research is bolstered by quantitative, model-based and mechanistic understanding of disease biology and pharmacology. Consequently core disciplines, including clinical pharmacology, pharmacogenomics, systems pharmacology, precision medicine, as well as others play an integral role in enabling translational research and translational medicine.

HSPs

Heat-shock proteins (HSPs), or stress proteins, are highly conserved and present in all organisms and in all cells of all organisms. Selected HSPs, also known as chaperones, play crucial roles in folding/unfolding of proteins, assembly of multiprotein complexes, transport/sorting of proteins into correct subcellular compartments, cell-cycle control and signalling, and protection of cells against stress/apoptosis. More recently, HSPs have been implicated in antigen presentation with the role of chaperoning and transferring antigenic peptides to the class I and class II molecules of the major histocompatibility complexes. In addition, extracellular HSPs can stimulate professional antigen-presenting cells of the immune system, such as macrophages and dendritic cells. HSPs constitute a large family of proteins that are often classified based on their molecular weight: hsp10, hsp40, hsp60, hsp70, hsp90, etc.

Our HSPs research focuses on 2 areas: Neurocognitive disorders (NCDs), other Neurodegenerative disorders, Cancers.

Selected references

Jaattela M. Heat shock proteins as cellular lifeguards. Ann. Med. 1999;31:261–271. doi: 10.3109/07853899908995889.

Jego G., Hazoume A., Seigneuric R., Garrido C. Targeting heat shock proteins in cancer. Cancer Lett. 2013;332:275–285. doi: 10.1016/j.canlet.2010.10.014.

Macario A.J., Conway de Macario E. Molecular chaperones: Multiple functions pathologies and potential applications. Front. Biosci. A J. Virtual Libr. 2007;12:2588–2600. doi: 10.2741/2257.

Heat shock proteins in neurodegenerative diseases: pathogenic roles and therapeutic implications.
Adachi H1, Katsuno M, Waza M, Minamiyama M, Tanaka F, Sobue G. DOI: 10.3109/02656730903315823

Jolly C., Morimoto R.I. Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J. Natl. Cancer Inst. 2000;92:1564–1572. doi: 10.1093/jnci/92.19.1564.

Ciocca D.R., Calderwood S.K. Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones. 2005;10:86–103. doi: 10.1379/CSC-99r.1.

Aridon P, Geraci F, Turturici G, D’Amelio M, Savettieri G, Sconzo G. Protective role of heat shock proteins in Parkinson’s disease. Neurodegener Dis. 2011;8:155–68.

Cohen IR. Autoimmunity to chaperonins in the pathogenesis of arthritis and diabetes. Annu Rev Immunol 1991; 9:567–589.

Hydrogen medicine

The potential of molecular hydrogen (H2) for preventive and therapeutic applications.
H2 has been accepted to be an inert and nonfunctional molecule in our body. H2 reacts with strong oxidants such as hydroxyl radical in cells and proposes its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signalling reactive oxygen species; therefore, there should be no or little adverse effects of H2.
The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.

Our H2 research focuses on 3 areas: Metabolic syndrome, Neurocognitive disorders (NCDs), other Neurodegenerative disorders, Cancers.

Selective references

Kikkawa YS, Nakagawa T, Horie RT, Ito J. Hydrogen protects auditory hair cells from free radicals. Neuroreport. 2009;20:689–94.

Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359–407

Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J. Am. Coll. Nutr. 2001;20:464S–72S.

Kawasaki H, Guan J, Tamama K. Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochem Biophys Res Commun. 2010;397:608–13.

Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004;10(Suppl):S18–25

Ohta S, Ohsawa I. Dysfunction of mitochondria and oxidative stress in the pathogenesis of Alzheimer’s disease: on defects in the cytochrome c oxidase complex and aldehyde detoxification. J Alzheimers Dis. 2006;9:155–66

Brambilla D, Mancuso C, Scuderi MR, et al. The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment of the risk/benefit profile. Nutr J. 2008;7:29.

Cross AH, Tuohy VK, Raine CS. Development of reactivity to new myelin antigens during chronic relapsing autoimmune demyelination. Cell Immunol 1993; 146(2):261–269.

Drug Repurposing

Drug repurposing generally refers to studying drugs that are already approved to treat one disease or condition to see if they are safe and effective for treating other diseases. Many agents approved for other uses already have been tested in humans, so detailed information is available on their pharmacology, formulation and potential toxicity. Because repurposing builds upon previous research and development efforts, new candidate therapies could be ready for clinical trials quickly, speeding their review by the EMA / FDA and, if approved, their integration into health care.
Discoveries about the molecular basis of disease provide unprecedented opportunities to translate research findings into new medicines. However, developing a brand-new drug takes an enormous amount of time, money and effort, mainly due to bottlenecks in the therapeutic development process. Delays and barriers mean that translation of a promising molecule into an approved drug often takes more than 14 years. It is crucial to advance strategies to reduce this time frame, decrease costs and improve success rates.

Our Drug Repurposing research focuses on various disorders.

Selective references

Nosengo N. Can you teach old drugs new tricks? Nature. 2016;534:314–316.

Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat Biotechnol. 2014;32:40–51.

Wei Sun, Philip Sanderson, and Wei Zheng Drug combination therapy increases successful drug repositioning  10.1016/j.drudis.2016.05.015

Zhang H. Y., Tang X. C. Neuroprotective effects of huperzine A: new therapeutic targets for neurodegenerative disease. Trends in Pharmacological Sciences2006;27(12):619–625. doi: 10.1016/j.tips.2006.10.004.

Carley DW. Drug repurposing: identify, develop and commercialize new uses for existing or abandoned drugs. Part I. IDrugs. 2005;8(4):306–309.

Weir SJ, DeGennaro LJ, Austin CP. Repurposing approved and abandoned drugs for the treatment and prevention of cancer through public-private partnership. Cancer Res. 2012;72(5):1055–1058.

Thayer A. Drug repurposing. Chem Eng News. 2012;90:15–25.

Huang R, et al. The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics. Sci Transl Med. 2011;3:80ps16–80ps16.

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