The focus of my research is to understand the biological role of endocrine factors in mammalian physiology and pathology with regard to regulatory signals that control processes connecting the cardiovascular, renal, skeletal, endocrine, and hematopoietic systems. Specifically, we study the molecular and cellular pathways that link fibroblast growth factor-23 (FGF23) in the pathogenesis of chronic diseases such as chronic kidney disease, heart disease, obesity, and diabetes by studying the interplay between the skeleton and the cardio-renal system through mineral homeostasis, whole-body energy and glucose metabolism, hematopoiesis, and other processes. In addition, we study the mechanisms by which bone interacts with the bone marrow environment and how the mineral content of bone influences the fate of hematopoietic stem cells.

FGF23 is an exciting hormone widely recognized as a major regulator of phosphate and vitamin D homeostasis and bone mineralization. High levels of FGF23 have been associated with hypophosphatemic rickets in children and adults, but also chronic kidney disease (CKD), left ventricular hypertrophy, and cardiovascular disease (CVD), highlighting the importance of FGF23 in well-being and pathological conditions. Importantly we were the first to report that high FGF23 levels in mice are associated with a decrease in the hematopoietic stem cell (HSC) pool size and particularly RBC production, whereas genetic inactivation of Fgf23 results in expansion of the HSC niche and selectively of the erythroid lineage. Notwithstanding, these hematopoietic changes are also detected prenatally in fetal livers of Fgf23-/- mice, indicating a role for FGF23 in HSC commitment to the erythroid lineage during embryonic development. Importantly, we were the first to report that inhibition of FGF23 signaling ameliorates inflammation and corrects iron deficiency and anemia in a mouse model of renal failure, but also in acute inflammation in mice with normal kidney function. These findings have high impact on the current diagnostic and therapeutic approaches for CKD- and CVD-associated anemia and iron deficiency and, in general, for disorders, associated with aberrant erythropoiesis and iron homeostasis.

For our studies we use genetically altered mouse models and pharmacologic inhibitors of FGF23 signaling, and employ a variety of approaches including generation of bone marrow chimeras, molecular biology, biochemistry, histology, immunohistochemistry, flow cytometry, and cell culture.