Online ISSN: 2515-8260

Author : Higgins, Paul J.


Translational Medicine definition by the European Society for Translational Medicine

Randall J. Cohrs; Tyler Martin; Parviz Ghahramani; Luc Bidaut; Paul J. Higgins; Aamir Shahzad

European Journal of Molecular & Clinical Medicine, 2015, Volume 2, Issue 3, Pages 86-88

Progress in the field of translational medicine (TM) within the last decade attests to the importance of the TM initiative in the context of more traditional academic health science centers. In many instances, these advancements have taken place without a clear definition of TM, which signifies the urgent need for a clear, consensus definition that would serve as an integrative blueprint for the various “versions” of TM definition. The various existing definitions are reflecting the diversity of institutional translational research and deployment programs. The European Society for Translational Medicine (EUSTM) is a global non-profit and neutral society whose principal objective is to enhance world-wide healthcare through the specific development and eventual clinical implementation and exploitation of TM-based approaches, resources and expertise. In this position article, the EUSTM defines TM as an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside and community. The goal of TM is to combine disciplines, resources, expertise, and techniques within these pillars to promote enhancements in prevention, diagnosis, and therapies. Accordingly, TM is a highly interdisciplinary field, the primary goal of which is to coalesce assets of various natures within the individual pillars in order to improve the global healthcare system significantly.

Accredited translational medicine centre: Human renal fibrotic disease: Translational research at the Center for Cell Biology and Cancer Research (CCBCR), Albany Medical College, Albany, NY

Paul J. Higgins; Aamir Shahzad; Jeffrey Kennedy

European Journal of Molecular & Clinical Medicine, 2015, Volume 2, Issue 2, Pages 51-54

Translational studies conducted in the Center for Cell Biology & Cancer Research at the Albany Medical College integrate the discovery of basic mechanisms underlying the development of human fibrotic disease with in vivo interventional strategies and tissue repair outcomes in animal models. This structured research program is expected to lead to the clinical adaptation of novel therapies specifically directed to the control of pathologically-relevant profibrotic genes in several organ systems. Perhaps the most mature, clinically-relevant, multidisciplinary effort focuses on molecular events underlying the pathophysiology of the renal fibrotic response to tissue injury. This program involves a network of collaborating urological surgeons, nephrologists, graduate students, pathologists, residents, transplant surgeons, basic scientists and molecular biologists and is built on a highly-collaborative framework that fosters translational interactions. This cooperative enterprise resulted in a new appreciation for the complexity of the TGF-β1-activated pathways leading to fibrotic gene expression in an in vivo model of renal injury that mimics obstructive uropathy in humans. Moreover, we have uncovered new, translationally-relevant and therapeutically-accessible, molecular targets. These are the focus of current pre-clinical studies with the goal being to assess their potential utility in the therapy of human renal fibrotic disease. Focal points: Interstitial fibrosis is a progressive disorder that frequently results in organ failure; current treatments are limited and largely ineffective. The majority of fibrotic diseases are irreversible and eventually fatal. Regardless of etiology, elevated tissue TGF-β1 levels and transcription of TGF-β1-responsive genes are linked to the activation of profibrotic signaling pathways. Plasminogen activator inhibitor-1(PAI-1) is a major causative factor in several clinically significant fibrotic syndromes. Translational research in the Center for Cell Biology & Cancer Research at Albany Medical College focuses on molecular events underlying transcriptional control of the profibrotic PAI-1 gene using an animal model of obstructive uropathy. The need for novel targeted approaches for the treatment of fibrosis highlights the clinical potential in the current probe of molecular mechanisms underlying TGF-β1-regulated PAI-1 gene control.

Small molecule PAI-1 functional inhibitor attenuates vascular smooth muscle cell migration and survival: Implications for the therapy of vascular disease

Tessa M. Simone; Paul J. Higgins

European Journal of Molecular & Clinical Medicine, 2014, Volume 2, Issue 1, Pages 16-19

Focal points • Bedside Targeted pharmacologic disruption of PAI-1 function with small molecule inhibitors may have general applicability for the treatment of fibroproliferative disorders, in general, and vascular disease, in particular. The development orally compatible drugs would likely simplify delivery and patient compliance. • Benchside It is apparent that PAI-1 is a multi-functional SERPIN, affecting such diverse physiological and pathophysiological processes as smooth muscle cell growth, migration, survival and pericellular proteolysis activity. Clearly, PAI-1 functional blockade has widespread clinical implications that are not restricted to one aspect of the tissue response to injury. • Industry The original small molecule panel of PAI-1 inhibitors derived from a collaboration between basic scientists and, largely, cardiovascular disease-oriented medical chemists as well as pharmaceutical investigators. This collegial relationship is expected to expand as it is evident that PAI-1 inhibition has generally utility in the treatment of cardiovascular diseases, tissue fibrosis (in particular, the renal and pulmonary systems) and cancer.