The goals of this project are to train Kurt Prins MD, PhD as a physician-scientist in Cardiology and advance the understanding of right ventricular dysfunction in pulmonary arterial hypertension (PAH). Dr. Prins is currently a third year Cardiology fellow in the Physician-Scientist Training Program, a combined research and clinical track dedicated to training the next generation of physician-scientist at the University of Minnesota. Dr. Prins has elected to conduct his research training in the laboratory of Dr. Joseph Metzger, a leader in molecular cardiac physiology who has a long track record of obtaining NIH funding and experience training physician-scientists. Dr. Prins has chosen two experts in pulmonary arterial hypertension research: Drs. Stephen Archer and E. Kenneth Weir to be on his mentoring committee to further guide him in his early career. Dr. Prins? educational objectives include gaining expertise in cardiac physiology by working in a lab of an established investigator in cardiology and collaborating with an expert in PAH, attending seminars to gain further exposure to outside investigators and build collaborations, and taking courses to prepare for future grant applications. The research project will investigate two distinct mechanisms of junctophilin-2 misregulation that contribute to right ventricular dysfunction in PAH. Dr. Prins authored a manuscript that showed increased microtubule density was associated with junctophilin-2 misregulation resulting in t-tubule disruptions and calcium mishandling in Duchenne cardiomyopathy. Now he will define the role of junctophilin-2 in RV dysfunction in PAH, a disease that he has worked to specialize in clinically. Thus, this proposed training period will allow Dr. Prins to combine his basic science and clinical interests by studying the link between junctophilin-2 misregulation due to improper trafficking on a pathologically remodeled microtubule cytoskeleton and miR-24-mediated repression and RV dysfunction in PAH. The project will determine if misregulation of junctophilin-2 leads to altered t-tubule structure, calcium mishandling, and ultimately RV dysfunction in pulmonary arterial hypertension. Also, it will also test the hypothesis that normalizing junctophilin-2 with colchicine treatment and by inhibiting miR-24 could be novel therapeutic strategies to improve RV function in PAH.
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 studying right ventricular dysfunction in pulmonary arterial hypertension. His training will be necessary to develop a new skill set that will allow for successful transition to an independently funded physician-scientist.
| 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 : |
| 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 : |
