Nicholas R. Ferreri, Ph.D.
Professor of Pharmacology
Course Director, Molecular Pharmacology
Department of Pharmacology
Basic Science Building, Rm. 505
15 Dana Road
Valhalla, NY 10595
Mechanisms that regulate salt and water transport in the kidney are critical to understanding the development of hypertension. Accordingly, the laboratory is uncovering features of a novel cytokine-based mechanism that interacts with eicosanoids to control sodium and chloride reabsorption in the medullary thick ascending limb of Henle (mTAL), a nephron segment that reabsorbs 25% of filtered NaCl and is the site of action of 'loop' diuretics. We investigate the role of tumor necrosis factor-alpha (TNF) in the context of hypertension and assess renal function and damage using multidisciplinary approaches. The regulation of blood pressure, sodium excretion, and renal inflammation is evaluated in vivo using genetic and lentivirus-silencing approaches. These studies are supported by in vitro cellular and molecular models utilizing freshly isolated mTAL tubules or primary cultures of mTAL cells that allow for a direct assessment of TNF components on the activity and expression of ion transport pathways and cyclooxygenase-2-dependent prostaglandin formation. The role of NFAT5, an isoform of the nuclear factor of activated T cell (NFAT) family of transcription factors, as a regulator of TNF production in the TAL and protective factor in acute kidney injury also is a major focus of the laboratory.
- Hao, S., M. Hao, and N.R. Ferreri. 2018. Renal-Specific Silencing of TNF (Tumor Necrosis Factor) Unmasks Salt-Dependent Increases in Blood Pressure via an NKCC2A (Na+-K+-2Cl− Cotransporter Isoform A)-Dependent Mechanism. Hypertension 71:1117-1125.
- Graham, L.A., A. Aman, D.D. Campbell, J. Augley, D. Graham, M.W. McBride, N.J. Fraser, N.R. Ferreri, A.F. Dominiczak, and S. Padmanabhan. 2018. Salt stress in the renal tubules is linked to TAL specific expression of uromodulin and an upregulation of heat shock genes. Physiological Genomics Sep 14. doi: 10.1152/physiolgenomics.00057.2018. [Epub ahead of print]
- Graham, L.A., A.F. Dominiczak, and N.R. Ferreri. 2017. The role of renal transporters and novel regulatory interactions in the TAL that control blood pressure. Physiological Genomics 49: 261-276.
- Hao S, DelliPizzi A, Quiroz-Munoz M, Jiang H, Ferreri NR. The EP3 receptor regulates water excretion in response to high salt intake. Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F822-F829.
- Hao S, Hernandez A, Quiroz-Munoz M, Cespedes C, Vio CP, Ferreri NR. PGE(2) EP(3) receptor downregulates COX-2 expression in the medullary thick ascending limb induced by hypertonic NaCl. Am J Physiol Renal Physiol. 2014 Sep 15;307(6):F736-46.
- Hao S, Bellner L, Zhao H, Ratliff BB, Darzynkiewicz Z, Vio CP, Ferreri NR. NFAT5 is protective against ischemic acute kidney injury. Hypertension 63(3):e46-52, 2014.
- Graham LA, Padmanabhan S, Fraser NJ, Kumar S, Bates JM, Raffi HS, Welsh P, Beattie W, Hao S, Leh S, Hultstrom M, Ferreri NR, Dominiczak AF, Graham D, McBride MW. Validation of uromodulin as a candidate gene for human essential hypertension. 63(3):551-8, 2014.
- Hao S, Bellner L, Ferreri NR. NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake. J. Physiol. Renal Physiol. 304(5):F533-42, 2013
- Battula S, Hao S, Pedraza PL, Stier CT, and Ferreri NR. Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia. Prostaglandins Other Lipid Mediat. 99(1-2):45-50, 2012.
PubMed Publications - Nicholas R. Ferreri, Ph.D.