The foremost objective of my career is to become an independent and successful physician-scientist in the field of cardiovascular complications of chronic kidney disease (CKD). My passion to achieve this objective has helped me since my training began as a medical student in Hungary. To enrich my experience, knowledge and skills I pursued a PhD degree and worked relentlessly to establish the beginning of my career in U.S. Continuing on the same path, I was selected in the ABIM research pathway at UAB, a competitive combined program for residency, fellowship and research training. To fully achieve the goals of my career with an overall emphasis on improving the health of patients with kidney diseases, I will need further training and mentorship that will also serve as a fundamental requisite for successful completion of the following scientific premise: Calcification of the vasculature is commonly found in patients with advanced CKD and is associated with increased morbidity and mortality. There is hence an urgent unmet need to find answers to etiologic and mechanistic questions in order to introduce novel therapeutics. Advanced CKD often results in phosphate retention and iron deficiency anemia. Whether such iron deficiency in advanced CKD patients promotes vascular calcification has not been elucidated. We previously reported that iron and 3H-1,2-Dithiole-3-thione (D3T) induced expression of intracellular ferritin heavy chain (FtH) mitigates transformation of vascular smooth muscle cells into osteoblast like cells. Based on our preliminary findings, we hypothesize that derangements in iron metabolism with subsequent decrements in intracellular FtH expression, accelerate CKD associated vascular calcification. In support of this concept, we hypothesize that parenteral iron administration may be considered to correct anemia and to prevent vascular calcification in CKD patients. We will also examine the exciting potential of D3T (a chemo-preventive agent and FtH stimulant), as a therapeutic/preventive agent against vascular calcification. In this study, we will utilize novel transgenic mice with conditional deletion of FtH in the vascular smooth muscle cell compartment to test this hypothesis in a model of CKD and hyperphosphatemia. Additionally, to fully understand the inhibitory role of FtH, we will utilize an unbiased analysis of gene expression using RNA seq and examine pathways that are involved in the vascular protective effects of FtH. Of equal importance, this proposal will serve as a comprehensive strategy intended to transition me from trainee to independent investigator. I present a curriculum designed to enhance 1) knowledge base in vascular biology, bioinformatics and biostatistics, 2) technical repertoire with a focus on translational techniques, 3) professional development through peer mentoring and gaining skills in laboratory management. This training will be under the guidance of accomplished and respected mentors in a high quality environment for scientific discovery and career development. I plan to take full advantage of this training award with the overall objective of providing meaningful contributions to improve health and outcomes of patients with CKD.

Public Health Relevance

Calcification of blood vessels is a major complication in patients with end stage kidney disease. In this proposal, how derangements in iron metabolism may facilitate calcification of blood vessels will be studied using a mouse model of kidney failure. The studies will focus on ferritin, a key iron storage protein, in the blood vessel wall and will examine the exciting novel approach to utilize parenteral iron for prevention and/or treatment of blood vessel calcification.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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NHLBI Mentored Clinical and Basic Science Review Committee (MCBS)
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Lidman, Karin Fredriksson
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University of Alabama Birmingham
Internal Medicine/Medicine
Schools of Medicine
United States
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