Pinelopi Kapitsinou, M.D.
Department of Internal Medicine, Division of Nephrology and Hypertension
M.D., Medical School, National and Kapodestrian University of Athens (Summa Cum Laude)
Internal Medicine Residency, Jacobi Medical Center / Albert Einstein College of Medicine
Clinical Fellowship in Nephrology, University of Pennsylvania
Postdoctoral Fellowship, Vanderbilt University
Hypoxic preconditioning and vascular biology in kidney disease
All areas of general nephrology, including chronic kidney diseases, nephrolithiasis, refractory hypertension and electrolyte disorders.
The focus of my lab's research is to understand the molecular mechanisms that dictate tolerance to hypoxic kidney injury and to translate these findings for novel diagnostic and therapeutic approaches. Because of its specialized vascular anatomy and the relatively low tissue pO2 levels, the kidney is particularly susceptible and responsive to hypoxia. Central mediators of systemic and cellular adaptation to O2 deprivation are hypoxia-inducible transcription factors HIF-1and HIF-2, whose activity is regulated by proyl hydroxylase domain-containing enzymes (PHDs). To link the hypoxia-elicited adaptive responses to kidney injury, we have two areas of research:
- The endothelial cell (EC) metabolic reprogramming mediated by PHD2/HIF-2 in post-ischemic kidney injury and repair. Our prior studies have demonstrated a critical role for EC HIF-2 in ischemic kidney injury through regulation of inflammation. We further explore the effects of PHD2/HIF-2 axis on kidney injury by using novel transgenic mice in which endothelial HIF-2 is upregulated by PHD2 loss. To assess the effect of endothelial PHD2/HIF-2 in kidney repair, we are using a transgenic model of inducible recombination in the endothelium. Importantly, we hypothesize that the PHD2/HIF-2 mediated responses in injury and repair involve a critical metabolic reprogramming. We are exploring the effects of HIF on metabolism by profiling metabolites, analyzing mitochondrial content and function, assessing oxidative phosphorylation via substrate/inhibitor titration protocols and performing targeted metabolic interference studies.
- HIF-induced systemic metabolic responses as mediators of tolerance to hypoxia/ischemia. To identify the biological pathways involved in mediating hypoxia tolerance, we perform an integrative metabolomic analysis of settings in which hypoxia is encountered; mouse models of hypoxia with samples from humans exposed to hypoxia (high altitude) or remote ischemic preconditioning. Common "hits" from these hypothesis-generating studies are the focus of mechanistic studies examining the contribution of specific metabolic pathways in hypoxia tolerance in the context of kidney injury.
Ganeshkumar Rajendran PhD, Postdoctoral fellow
Michael P. Schonfeld MSc, Research assistant
- P.P. Kapitsinou and V.H. Haase. The VHL tumor suppressor and HIF: Insights from genetic studies in mice. Cell Death & Differentiation. 15: 650-9, 2008
- P.P. Kapitsinou, Q. Liu, T Unger, J. Rha, O. Davidoff, B Keith, J.A. Epstein, S.L. Moores C.L. Erickson Miller, and V. H. Haase: Hepatic HIF-2α regulates erythropoietic responses to hypoxia in renal anemia. Blood. 116:3039-48, 2010 (commentary by Terry Lappin in the same issue of Blood, Journal Club/Kidney International)
- P. P. Kapitsinou, J. Jaffe, M. Michael, C. E. Swan, K. J. Duffy, C. L. Erickson-Miller and V. H. Haase. Preischemic Targeting of HIF Prolyl Hydroxylation Inhibits Fibrosis associated with Acute Kidney Injury. Am J Physiol Renal Physiology. 302:F1172-9, 2012
- H. Kobayashi, V. Gilbert, Q. Liu, P.P. Kapitsinou, T. L. Unger, J. Rha, S. Rivella, D. Schlöndorff, and V. H. Haase. Myeloid cell-derived HIF suppresses renal inflammation. J. Immunol. 188:5106-15, 2012
- P. P. Kapitsinou, H. Sano, M. Michael, H. Kobayashi, O. Davidoff, C. L. Erickson-Miller, K. J. Duffy, T. A. Sutton, and V. H. Haase. Hypoxia-inducible factor-2 in endothelial cells mediates protection and recovery from ischemic kidney injury. J Clin Invest. 124:2396-409, 2014
- P.P. Kapitsinou and V.H. Haase. Molecular Mechanisms of Ischemic Preconditioning. Am J Physiol Renal Physiology 2015 Aug 26:ajprenal.00224.2015
Oct 26, 2015