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 #
2T32HL110849-06
Application #
9208921
Study Section
Special Emphasis Panel (NITM (OA))
Program Officer
Colombini-Hatch, Sandra
Project Start
2012-04-01
Project End
2022-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
6
Fiscal Year
2017
Total Cost
$335,915
Indirect Cost
$21,327
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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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