Biomedical investigators are experiencing a limitation in their collective ability to translate the remarkable basic science discoveries of the current era into the clinical arena?a divide appropriately termed ?the valley of death.? In our first cycle of funding, we developed a novel training program in bench-to-bedside research methodology designed to train the next generation of clinical and basic researchers in translational approaches to pulmonary vascular biology and medicine. Our first eight trainees have had considerable success in publications, grant funding, and securing academic positions; two of the trainees were underrepresented minorities and six were women. In response to feedback from our current trainees and advisory boards, and in an effort to address the increasing pressure from the NIH, political leaders, and the public to translate basic discovery into therapeutic applications that positively change lives, we will extend the scope of our program in this second cycle of funding to incorporate entrepreneurial training, including: 1) development of a novel joint University of Pittsburgh (ranked #5 in NIH funding)-Carnegie Mellon University MBA Program (ranked #1 in part-time programs) in Entrepreneurship; 2) elective rotations focused on commercialization of biotechnology; and 3) an expanded faculty that includes translational scientist-entrepreneurs. We have created separate milestone-driven Translational Tracks and Entrepreneurial Tracks, but retaining the option for trainees to customize an Individual Development Plan to include components of either track. Trainees will be co-mentored by faculty with complementary research approaches to provide comprehensive training, and projects focused on patient-oriented bench-to-bedside (T1) research, with constant attention to trainee career development. Our faculty include translationally-focused pulmonologists, cardiologists, vascular surgeons, and PhDs spanning basic science to entrepreneurship, with a history of scientific productivity in pulmonary vascular biology, excellent funding support, successful mentoring, and expertise from drug discovery to commercialization of biotechnology. Substantial institutional support and resources are available through endowments to the VMI and a translational program project grant directed by Dr. Gladwin. The proposed training program, leadership, advisory boards, training faculty, and infrastructure at the University of Pittsburgh are strongly positioned to build on an already rich bench-to-bedside translational training program and create a generation of researchers committed to spanning the ?valley of death? between basic research discoveries, clinical application, and commercial viability in pulmonary vascular disease.

Public Health Relevance

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 translational patient- oriented research, drug development, and commercialization of basic discoveries. The scientific focus in on the study of high blood pressure in the lungs, an important and common complication of many heart and lung diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Institutional National Research Service Award (T32)
Project #
5T32HL110849-08
Application #
9662834
Study Section
NHLBI Institutional Training Mechanism Review Committee (NITM)
Program Officer
Kalantari, Roya
Project Start
2012-04-01
Project End
2022-03-31
Budget Start
2019-04-01
Budget End
2020-03-31
Support Year
8
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15260
Machin, Nicoletta; Ragni, Margaret V (2018) An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B. J Blood Med 9:135-140
Thapa, Dharendra; Stoner, Michael W; Zhang, Manling et al. (2018) Adropin regulates pyruvate dehydrogenase in cardiac cells via a novel GPCR-MAPK-PDK4 signaling pathway. Redox Biol 18:25-32
Remy, Kenneth E; Cortés-Puch, Irene; Solomon, Steven B et al. (2018) Haptoglobin improves shock, lung injury, and survival in canine pneumonia. JCI Insight 3:
Machin, Nicoletta; Ragni, Margaret V (2018) Measuring success in hemophilia gene therapy using a factor level & outcomes yardstick. Expert Rev Hematol 11:83-86
Thapa, Dharendra; Wu, Kaiyuan; Stoner, Michael W et al. (2018) The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial ?-oxidation enzyme HADHA. J Biol Chem 293:17676-17684
Rose, Jason J; Nouraie, Mehdi; Gauthier, Marc C et al. (2018) Clinical Outcomes and Mortality Impact of Hyperbaric Oxygen Therapy in Patients With Carbon Monoxide Poisoning. Crit Care Med 46:e649-e655
Machin, Nicoletta; Ragni, Margaret V; Smith, Kenneth J (2018) Gene therapy in hemophilia A: a cost-effectiveness analysis. Blood Adv 2:1792-1798
Potoka, Karin P; Wood, Katherine C; Baust, Jeffrey J et al. (2018) Nitric Oxide-Independent Soluble Guanylate Cyclase Activation Improves Vascular Function and Cardiac Remodeling in Sickle Cell Disease. Am J Respir Cell Mol Biol 58:636-647
Vanderpool, Rebecca R; Saul, Melissa; Nouraie, Mehdi et al. (2018) Association Between Hemodynamic Markers of Pulmonary Hypertension and Outcomes in Heart Failure With Preserved Ejection Fraction. JAMA Cardiol 3:298-306
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:

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