Current Funding
Functional Significance of Ferritin Light Chain in Sepsis-associated Kidney Injury
National Institute of Diabetes and Digestive and Kidney Diseases, R01 DK122986
Sepsis is an overwhelming inflammatory response to infection and is the most common cause of kidney injury in intensive care units. Serum ferritin light chain (FtL) is elevated during sepsis but the contributory role thereof in inflammation is not known; therefore, the overall goal of this study is to evaluate the role of FtL in mitigating the sepsis- induced hyperinflammatory response and kidney injury.
Epigenetic Regulation of Kidney Fibrosis following AKI
National Institute of Diabetes and Digestive and Kidney Diseases, R01 DK126664 (Co-Investigator)
Patients requiring cardiac or vascular surgery often have brief reductions in blood flow to the kidneys, which unfortunately can result in kidney injury, decreased kidney function, development of chronic kidney disease, and/or death. In this setting, kidney histone deacetylase enzymes and mircoRNA are activated and may lead to excessive scarring in the kidney. The purpose of this proposal is to determine the epigenetic regulation of myofibroblast activation following kidney injury leading to chronic kidney disease transition.
The role of ferritin in polycystic kidney disease
PKD Foundation grant, 905894 (Co-Investigator)
The overall goal of this proposal is to determine the effects of site-specific expression of ferritin and iron in regulating cystic growth and progression of polycystic kidney disease.
Molecular and Cellular Pathogenesis of Kidney Disease in Sickle Cell Disorders
National Institute of Diabetes and Digestive and Kidney Diseases, R01 DK124426 (Co-Investigator)
Kidney disorders including acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal diseases (ESRD) are prevalent in sickle cell disease (SCD) and account for significant morbidity and mortality in this patient population. Incidences of AKI, compelling risk factors for CKD and ESRD, are major clinical concerns among SCD patients hospitalized for acute hemolytic crisis. Enhanced clearance of excess circulating heme to the kidneys during hemolysis promotes clinically relevant AKI in murine model of SCD. The role of altered heme scavenging system, clearing free circulating heme, in the pathogenesis of AKI is unknown. This project will determine i) the association of two heme scavengers, hemopexin and alpha-1-microglobulin, with AKI in SCD patients, ii) the mechanism by which heme regulates the biosynthesis of heme scavengers, and iii) the putative pathway that impairs heme degradation by heme oxygensase-1 in SCD kidneys. This proposal will determine if ratio of plasma heme scavengers’ concentration serves as a prognostic risk factor for AKI in SCD. The results of this proposal will also identify specific intermediate therapeutic targets to block AKI pathogenesis in order to improve adverse outcomes of kidney injuries in SCD.
Mononuclear phagocytes in the pathogenesis of acute kidney injury
National Institute of Diabetes and Digestive and Kidney Diseases, R01 DK118932 (Co-Investigator)
Acute kidney injury (AKI) is a major health problem for hospitalized patients, especially those in intensive care units where mortality among such patients can be as high as 80%. The studies described in this proposal will investigate the role of renal mononuclear phagocytes, which have been known to exist within the kidney for nearly 40 years, but have only recently been determined to play a role in AKI and normal kidney function. We will determine the origin and function of these cells in the kidney and the roles that they play in the initial injury and the repair processes after AKI.
Regulation of macrophage phenotype by ferritin heavy chain in CKD
National Institute of Diabetes and Digestive and Kidney Diseases, R01 DK134402 (Co-Investigator)
Chronic kidney disease (CKD) is a significant public health challenge and a substantial cause of mortality, morbidity, and health care expenditure. The goal of this project is to decipher how dysregulated iron metabolism, a hallmark of CKD, may impact the course and progression of CKD. The studies will focus on ferritin, a key iron storage protein, in the macrophages and will examine the exciting novel approach of targeting macrophage ferritin expression to diminish CKD.
