Nicholas R. Ferreri, Ph.D.
Professor of Pharmacology
- Molecular Pharmacology
Department of Pharmacology
Basic Science Building, Rm. 505
15 Dana Road
Valhalla, NY 10595
Hypertension is an important risk factor for the development of heart disease, stroke, and kidney disease that affects greater than 40% of the population in the United States. Many hypertensive patients, especially African Americans, exhibit sensitivity to salt. Mechanisms that regulate salt and water transport in the kidney are critical to understanding the development of hypertension. Our laboratory is uncovering features of a novel intratubular tumor necrosis factor-alpha (TNF) system that is part of an adaptive mechanism that regulates NaCl reabsorption and blood pressure (BP) homeostasis. The production of TNF within the kidney is increased by high salt (HS) intake and decreased by low salt (LS) intake, suggesting that it may be important in salt-dependent forms of hypertension and other conditions in which salt concentrations are altered. Genetic and molecular approaches are currently being used to determine how TNF released from renal epithelial cells elicits regulatory effects in the kidney and interacts with inflammatory cells that infiltrate the kidney in response to elevated blood pressure. We recently showed that TNF inhibits intrarenal expression of angiotensinogen (AGT) by a miRNA-dependent mechanism suggesting that the intrarenal renin-angiotensin system (RAS) and TNF systems may interact with each other. The BP attenuating effect of TNF in response to HS intake is dependent upon inhibition of phospho-NKCC2 (pNKCC2) and NKCC2A expression and the molecular mechanisms that underlie these effects are currently being investigated. Collectively, the studies will define a novel intratubular regulatory system in which TNF production by renal tubular epithelial cells, in response to increases in salt intake, regulates NKCC2 isoform expression and function and contributes to BP homeostasis.
Education and post-graduate training profile:
Associate Research Scientist: Yale University, Department of Allergy and Clinical Immunology, New Haven, CT
Post-doctoral fellow: The Scripps Research Institute, Department of Immunology, La Jolla, California
Graduate Degree Institution: New York Medical College, Valhalla, New York
Undergraduate Institution: Case Western Reserve University, Cleveland, Ohio
- Hao, S., J. Salzo, H. Zhao, M. Hao, Z. Darzynkiewicz, and N.R. Ferreri. 2020. MicroRNA-133a-dependent inhibition of proximal tubule angiotensinogen by renal TNF. Hypertension 76: 1744-1752.
- Hao, S., J. Salzo, M. Hao, and N.R. Ferreri. 2020. Regulation of NKCC2B by TNF-alpha in response to salt restriction. Am. J. Physiol. 318:F273-82.
- Mopidevi, B., I Sivankutty, S. Hao, N.R. Ferreri, and A. Kumar. 2020. Effects of intron-conversion in the human CYP11B2 gene on its transcription and blood pressure regulation in transgenic mice. J. Biol. Chem. 295:11068-11081.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. Hypertension. 63(3):551-8, 2014.
- Hao S, Bellner L, Ferreri NR. NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake. Am. J. Physiol. Renal Physiol. 304(5):F533-42, 2013
PubMed Publications - Nicholas R. Ferreri, Ph.D.