The goals of this project are to further train Kurt Prins MD, PhD as a physician-scientist in cardiology and advance the field of Duchenne cardiomyopathy. Dr. Prins is currently a Cardiology fellow in the Physician- Scientist Training Program at the University of Minnesota, a combined research and clinical track which dedicates three years of protected time for research and two years to clinical cardiology training. Dr. Prins has elected to continue his research training in the laboratory of Dr. Joseph Metzger, a world leader in cardiac physiology and Duchenne cardiomyopathy. Dr. Prins' educational objectives include gaining expertise in cardiac physiology by working in a lab of an established investigator in cardiology and attending seminars to gain further exposure to outside investigators and build possible collaborations. The research project will investigate the role of disorganized microtubules in Duchenne cardiomyopathy. Dr. Prins authored the manuscript that first described the dystrophin-microtubule interaction and he now looks to build on these findings by probing the cardiac-specific physiological consequences of disorganized microtubules. This project will study the link between microtubule disorganization with t-tubule disruptions and calcium handling abnormalities, and will also test the hypothesis that targeting microtubules with colchicine will be a novel therapy for Duchenne cardiomyopathy. If results are positive, this project will identify colchicine, an already FDA-approved medication, as a therapy for Duchenne cardiomyopathy and thus allow for quick translation into a Duchenne-orientated clinical trial. The training of Dr. Prins as physician-scientist will advance the mission of the NIH by creating a scientist that will conduct clinically relevant research.

Public Health Relevance

This proposal is designed to train Kurt Prins MD, PhD in molecular and cellular cardiac physiology to aid in transition to an independently funded physician-scientist in cardiology. His training will be necessary to develop a new skill set that wll enable him to carry out clinically-relevant research.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Meadows, Tawanna
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University of Minnesota Twin Cities
Internal Medicine/Medicine
Schools of Medicine
United States
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Rose, Lauren; Prins, Kurt W; Archer, Stephen L et al. (2018) Survival in pulmonary hypertension due to chronic lung disease: Influence of low diffusion capacity of the lungs for carbon monoxide. J Heart Lung Transplant :
Prins, Kurt W; Rose, Lauren; Archer, Stephen L et al. (2018) Disproportionate Right Ventricular Dysfunction and Poor Survival in Group 3 Pulmonary Hypertension. Am J Respir Crit Care Med 197:1496-1499
Law, Michelle L; Prins, Kurt W; Olander, Megan E et al. (2018) Exacerbation of dystrophic cardiomyopathy by phospholamban deficiency-mediated chronically increased cardiac Ca2+ cycling in vivo. Am J Physiol Heart Circ Physiol :
Prins, Kurt W; Archer, Stephen L; Pritzker, Marc et al. (2018) Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension. J Heart Lung Transplant 37:376-384
Prins, Kurt W; Duval, Sue; Markowitz, Jeremy et al. (2017) Chronic use of PAH-specific therapy in World Health Organization Group III Pulmonary Hypertension: a systematic review and meta-analysis. Pulm Circ 7:145-155
Prins, Kurt W; Tian, Lian; Wu, Danchen et al. (2017) Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension. J Am Heart Assoc 6:
Prins, Kurt W; Asp, Michelle L; Zhang, Huiliang et al. (2016) Microtubule-Mediated Misregulation of Junctophilin-2 Underlies T-Tubule Disruptions and Calcium Mishandling in mdx Mice. JACC Basic Transl Sci 1:122-130
Prins, Kurt W; Thenappan, Thenappan (2016) World Health Organization Group I Pulmonary Hypertension: Epidemiology and Pathophysiology. Cardiol Clin 34:363-74
Thenappan, Thenappan; Prins, Kurt W; Pritzker, Marc R et al. (2016) The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension. Ann Am Thorac Soc 13:276-84
Prins, Kurt W; Weir, E Kenneth; Archer, Stephen L et al. (2016) Pulmonary pulse wave transit time is associated with right ventricular-pulmonary artery coupling in pulmonary arterial hypertension. Pulm Circ 6:576-585

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