Biomedical investigators are witnessing a limitation in our collective ability to translate the remarkable basic science discoveries of the current era to the clinic. The divide between basic discovery and clinical application has been appropriately termed the valley of death. A dearth of both physician scientists focused on translational research and lack of training programs creatively focused on translational research methodologies compound this problem.
The aim of this program is to develop a novel training program in bench-to-bedside research methodology and to train the future generation of clinical and basic researchers in a translational approach to vascular biology, with a specific emphasis on the pulmonary circulation. While there are many T32 programs focused on systemic vascular biology, to our knowledge there is not a single program focused on Pulmonary Vascular Biology and Pulmonary hypertension. We have engineered a new approach to training in translational bench-to-bedside research, focused on providing the trainee with a translational research core competency tool-set, starting with immersion in a concentrated training period in translational research, that includes novel elective one-month rotations focused on pulmonary hypertension therapeutics at the FDA, intramural NIH Clinical Center Regulatory and Pharmacy Development Program, and Industry. With the fundamental tools for human subjects research in hand the trainee will then engage in a two-year intensive training fellowship with our translationally-oriented vascular biology and pulmonary hypertension mentors. The fellowship mentorship will include a basic-science oriented mentor paired with a clinical-science oriented mentor to provide for comprehensive training in basic science with the necessary application to the clinical and patient environment. Projects are focused on patient oriented bench-to-bedside (T1) research, with constant attention to trainee career development. Our faculty include 19 NIH funded investigators with a long- standing history of scientific productivity in pulmonary vascular biolog and successful mentoring. We also include 4 junior training faculty who are highly focused on pulmonary vascular research, are recent recipients of R-level NIH funding, and will be paired with senior mentors to maintain a continuous pipeline of faculty mentors. Substantial institutional support and resources are available through endowments to the VMI and a translational program project directed by Dr. Gladwin. The field of Pulmonary Vascular Biology has matured to the point that we can no longer rely on back door training for the next generation of pulmonary vascular researchers. The proposed training program and the existing investigators and infrastructure at The University of Pittsburgh are strongly positioned to create a novel and rich bench-to-bedside translational training program, designed to address the growing and severe valley of death between basic research discoveries and clinical application.
While there have been discoveries and advances in the biomedical sciences over the last two decades, from sequencing the human genome to the engineering of mouse models of human disease, we still face a steady decline in our collective ability to translate these remarkable basic science discoveries into new drugs and treatments for patients. The divide between basic discovery and clinical application has been appropriately termed 'the valley of death'. In this training program we address this challenge directly with a new and creative approach to training physicians and basic scientists in the essential tools for patient oriented research and drug development. We focus this approach on the study of high blood pressure in the lungs, an important and common complication of many heart and lung diseases.
|Meijles, Daniel N; Sahoo, Sanghamitra; Al Ghouleh, Imad et al. (2017) The matricellular protein TSP1 promotes human and mouse endothelial cell senescence through CD47 and Nox1. Sci Signal 10:|
|Gladwin, Mark T (2017) Translational Advances in the Field of Pulmonary Hypertension Bench to Bedside: How Fundamental Discoveries in Science Are Advancing Our Understanding and Therapy of Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 195:1-3|
|Kato, Gregory J; Steinberg, Martin H; Gladwin, Mark T (2017) Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest 127:750-760|
|Thapa, Dharendra; Zhang, Manling; Manning, Janet R et al. (2017) Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart. Am J Physiol Heart Circ Physiol 313:H265-H274|
|Bennewitz, Margaret F; Jimenez, Maritza A; Vats, Ravi et al. (2017) Lung vaso-occlusion in sickle cell disease mediated by arteriolar neutrophil-platelet microemboli. JCI Insight 2:e89761|
|Amdahl, Matthew B; Sparacino-Watkins, Courtney E; Corti, Paola et al. (2017) Efficient Reduction of Vertebrate Cytoglobins by the Cytochrome b5/Cytochrome b5 Reductase/NADH System. Biochemistry 56:3993-4004|
|Gladwin, Mark T (2017) How Red Blood Cells Process Nitric Oxide: Evidence for the Nitrite Hypothesis. Circulation 135:177-179|
|Owusu-Ansah, Amma; Ihunnah, Chibueze A; Walker, Aisha L et al. (2016) Inflammatory targets of therapy in sickle cell disease. Transl Res 167:281-97|
|Simon, Marc A; Vanderpool, Rebecca R; Nouraie, Mehdi et al. (2016) Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction. JCI Insight 1:e89620|
|Ghosh, Samit; Ihunnah, Chibueze A; Hazra, Rimi et al. (2016) Nonhematopoietic Nrf2 dominantly impedes adult progression of sickle cell anemia in mice. JCI Insight 1:|
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