Ph.D. 2005, Monash University
Specialty: Renal Physiology
Major Interest: The endothelin system in renal ischemia-reperfusion injury; Inflammatory cytokines and renal function;Hypertension; Lupus nephritis.
1. Contribution of endothelin-1 to renal ischemia-reperfusion injury.
Renal ischemia-reperfusion injury is a major cause of acute renal failure in surgical and trauma patients, and causes poor kidney function in renal transplant patients. Prominent and prolonged upregulation of the peptide endothelin-1 (ET-1) occurs in the kidney following ischemic insults. This multifunctional peptide is a powerful vasoconstrictor, and promotes inflammation and production of diverse mediators including nitric oxide, eicosanoids and reactive oxygen species. Dysfunction of the endothelin system has also been implicated in salt-sensitive hypertension, and survivors of acute renal failure are at increased risk of later developing hypertension. Our goal is to understand how ET-1 contributes to renal injury and dysfunction, both in the peri-ischemic period and as recovery progresses.
2. Iron accumulation and ER stress in Lupus Nephritis.
Lupus is a chronic, often debilitating autoimmune disease that predominantly affects young women. Damage to the kidneys (lupus nephritis) is a serious and common complication of Lupus, affecting approximately 50% of patients, and has been linked with poor patient prognosis and increased risk of premature death. This project focuses on a new possible cause of kidney injury in Lupus: iron accumulation in the kidney. Using a mouse model, we will determine (1) the contribution of increased iron accumulation to renal injury in lupus nephritis; (2) the pathway(s) by which increased iron accumulation occurs; and (3) the contribution of endoplasmic reticulum (ER) stress to renal injury in lupus nephritis. Our long-term goal is to uncover new treatment options for lupus nephritis.
3. Role of Eps15 homology domain-containing proteins in renal function.
Trafficking of cellular membrane proteins has an enormous impact on the activity of enzymes, transport of ions and other molecules across the cell membrane, and on the availability of cell surface receptors to interact with ligands. The Eps15 homology domain-containing (EHD) protein family is emerging as a critical regulator of endocytic trafficking and cell surface protein expression. The four members of this protein family (EHD1 through 4), are expressed in a cell- and nephron-segment specific manner in the kidney, however, their roles in renal physiology and in pathophysiological conditions are almost completely unknown. Our studies are aimed at determining the contribution of this novel family of proteins to renal function in health and disease.
- Cheema MU, Irsik DL, Wang Y, Miller-Little W, Hyndman KA, Marks ES, Frøkiær J, Boesen EI, Norregaard R. Estradiol regulates AQP2 expression in the collecting duct - a novel inhibitory role for estrogen receptor alpha. Am J Physiol Renal Physiol. 2015 Aug 15; 309(4):F305-17. PMID:26062878
- EI Boesen. Endothelin receptors, renal effects and blood pressure. Current Opinion in Pharmacology 21:25-34. 2015. PMID:2554397
- Merchen TD, Boesen EI, Gardner JR, Harbarger R, Kitamura E, Mellor A, Pollock DM, Ghaffari A, Podolsky R, Nahman NS Jr. Indoleamine 2, 3-dioxygenase inhibition alters the non-coding RNA transcriptome following renal ischemia-reperfusion injury. Transpl Immunol. 2014 May; 30(4):140-4. PMID: 24751756
- EI Boesen. Chronic elevation of IL-1b induces diuresis via a cyclo-oxygenase 2-mediated mechanism. American Journal of Physiology Renal Physiology 305:F189-F198, 2013. PMID: 23657858
- KA Hyndman, EI Boesen, AA Elmarakby, MW Brands, P Huang, DE Kohan, DM Pollock, JS Pollock. Renal collecting duct NOS1 maintains fluid-electrolyte homeostasis and blood pressure. Hypertension. 62(1):91-98, 2013. PMID: 23608660