Alicia A. McDonough

Alicia A. McDonough

Professor of Physiology and Neuroscience
Physiology and Biophysics
MMR 508 1333 San Pablo Street Health Sciences Campus Los Angeles

Case Western School of Medicine: Ulrich Hopfer Lectureship, 2019

University of Southern California: Phi Kappa Phi Faculty Recognition Award, 2018

American Physiological Society Epithelial Transport Group: Steve Hebert Lecturer, 2018

American Society of Nephrology: Robert W. Schrier Endowed Lectureship, 2017

KCVD Young Investigator Symposium: Keynote Speaker ANS Kidney Week, 2016

KCVD Young Investigator Symposium: Keynote Speaker ASN Kidney Week, 2016

Medical College of Wisconsin: J.J. Smith Endowed Lecture, 2016

Kansas State Univ. Veterinary Medicine: Clarenberg Distinguished Lecture, 2015

AHA Kidney in Cardiovascular Disease Council: Donald Seldin Lecture, 2014

SUNY Buffalo: Suk Ki Hong Memorial Lecturer, 2010

American Physiological Society: Ernest H. Starling Distinguished Lectureship, 2009

Keck School of Medicine: Outstanding Teaching Awards: '07, '12, '17, 2007-2018

Keck School of Medicine: Outstanding Teaching Award, 2007-2012

American Heart Association: Established Investigator Award, 1984-1989

Coordinate adaptations of skeletal muscle and kidney to adjust extracellular [K+] during K+ deficient diet in mice Am J Physiol Cell Physiol. 2020 Aug 26. . View in PubMed

Electrolyte and transporter responses to angiotensin II induced hypertension in female and male rats and mice Acta Physiol (Oxf). 2020 May; 229(1):e13448. . View in PubMed

a2A-Adrenoceptors Modulate Renal Sympathetic Neurotransmission and Protect against Hypertensive Kidney Disease J Am Soc Nephrol. 2020 Apr; 31(4):783-798. . View in PubMed

Impact of angiotensin II-mediated stimulation of sodium transporters in the nephron assessed by computational modeling Am J Physiol Renal Physiol. 2019 12 01; 317(6):F1656-F1668. . View in PubMed

Functional implications of the sex differences in transporter abundance along the rat nephron: modeling and analysis Am J Physiol Renal Physiol. 2019 12 01; 317(6):F1462-F1474. . View in PubMed

Blood pressure regulation by the angiotensin type 1 receptor in the proximal tubule Curr Opin Nephrol Hypertens. 2018 01; 27(1):1-7. . View in PubMed

Downregulation of the Cl-/HCO3-Exchanger Pendrin in Kidneys of Mice with Cystic Fibrosis: Role in the Pathogenesis of Metabolic Alkalosis Cell Physiol Biochem. 2018; 45(4):1551-1565. . View in PubMed

Functional implications of sexual dimorphism of transporter patterns along the rat proximal tubule: modeling and analysis Am J Physiol Renal Physiol. 2018 09 01; 315(3):F692-F700. . View in PubMed

Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice Am J Physiol Renal Physiol. 2017 Dec 01; 313(6):F1243-F1253. . View in PubMed

Collecting Duct Nitric Oxide Synthase 1ß Activation Maintains Sodium Homeostasis During High Sodium Intake Through Suppression of Aldosterone and Renal Angiotensin II Pathways J Am Heart Assoc. 2017 Oct 24; 6(10). . View in PubMed

Potassium Homeostasis: The Knowns, the Unknowns, and the Health Benefits Physiology (Bethesda). 2017 03; 32(2):100-111. . View in PubMed

Cardiovascular benefits associated with higher dietary K+ vslower dietary Na+: evidence from population and mechanistic studies. Am J Physiol Endocrinol Metab. 2017 04 01; 312(4):E348-E356. . View in PubMed

ISN Forefronts Symposium 2015: Maintaining Balance Under Pressure-Hypertension and the Proximal Tubule Kidney Int Rep. 2016 Sep; 1(3):166-176. . View in PubMed

Interleukin-1 Receptor Activation Potentiates Salt Reabsorption in Angiotensin II-Induced Hypertension via the NKCC2 Co-transporter in the Nephron Cell Metab. 2016 Feb 09; 23(2):360-8. . View in PubMed

Potassium Supplementation Prevents Sodium Chloride Cotransporter Stimulation During Angiotensin II Hypertension Hypertension. 2016 10; 68(4):904-12. . View in PubMed

Interleukin-17A Regulates Renal Sodium Transporters and Renal Injury in Angiotensin II-Induced Hypertension Hypertension. 2016 07; 68(1):167-74. . View in PubMed

Paracellular epithelial sodium transport maximizes energy efficiency in the kidney J Clin Invest. 2016 07 01; 126(7):2509-18. . View in PubMed

Proximal tubule NHE3 activity is inhibited by beta-arrestin-biased angiotensin II type 1 receptor signaling Am J Physiol Cell Physiol. 2015 Oct 15; 309(8):C541-50. . View in PubMed

Maintaining Balance Under Pressure: Integrated Regulation of Renal Transporters During Hypertension Hypertension. 2015 Sep; 66(3):450-5. . View in PubMed

Considerations when quantitating protein abundance by immunoblot Am J Physiol Cell Physiol. 2015 Mar 15; 308(6):C426-33. . View in PubMed

Am J Physiol Renal Physiol. 2014 Dec 01; 307(11):F1249-62. . View in PubMed

Paradoxical activation of the sodium chloride cotransporter (NCC) without hypertension in kidney deficient in a regulatory subunit of Na,K-ATPase, FXYD2 Physiol Rep. 2014 Dec 01; 2(12). . View in PubMed

Of mice and men: modeling cardiovascular complexity in diabetesFocus on "Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat heart". . 2014 Sep 15; 307(6):C497-8. . View in PubMed

Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis Am J Physiol Renal Physiol. 2014 May 01; 306(9):F1059-68. . View in PubMed

Compression injury in the mouse spinal cord elicits a specific proliferative response and distinct cell fate acquisition along rostro-caudal and dorso-ventral axes Neuroscience. 2013 Dec 19; 254:1-17. . View in PubMed

Differential regulation of Na+ transporters along nephron during ANG II-dependent hypertension: distal stimulation counteracted by proximal inhibition Am J Physiol Renal Physiol. 2013 Aug 15; 305(4):F510-9. . View in PubMed

J Mol Med (Berl). 2013 Aug; 91(8):951-63. . View in PubMed

Need to quickly excrete K(+)? Turn off NCC. Kidney Int. 2013 May; 83(5):779-82.. View in PubMed

Effects of ACE inhibition and ANG II stimulation on renal Na-Cl cotransporter distribution, phosphorylation, and membrane complex properties . 2013 Jan 15; 304(2):C147-63. . View in PubMed

Effects of K+-deficient diets with and without NaCl supplementation on Na+, K+, and H2O transporters' abundance along the nephron Am J Physiol Renal Physiol. 2012 Jul 01; 303(1):F92-104. . View in PubMed

How does potassium supplementation lower blood pressure? Am J Physiol Renal Physiol. 2012 May 01; 302(9):F1224-5.. View in PubMed

AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure Cell Metab. 2011 Apr 06; 13(4):469-475. . View in PubMed

Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure . 2010 Apr; 298(4):R851-61. . View in PubMed

Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilli Am J Physiol Renal Physiol. 2010 Jan; 298(1):F177-86. . View in PubMed

Motoring down the microvilliFocus on "PTH-induced internalization of apical membrane NaPi2a: role of actin and myosin VI". . 2009 Dec; 297(6):C1331-2. . View in PubMed

Isoform specificity of cardiac glycosides binding to human Na+,K+-ATPase alpha1beta1, alpha2beta1 and alpha3beta1 Eur J Pharmacol. 2009 Nov 10; 622(1-3):7-14. . View in PubMed

Narrative review: evolving concepts in potassium homeostasis and hypokalemia Ann Intern Med. 2009 May 05; 150(9):619-25. . View in PubMed

Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles Am J Physiol Renal Physiol. 2009 Apr; 296(4):F810-8. . View in PubMed

Recent advances in understanding integrative control of potassium homeostasis Annu Rev Physiol. 2009; 71:381-401. . View in PubMed

Rationale and design of CAPITA: a RCT of 13-valent conjugated pneumococcal vaccine efficacy among older adults Neth J Med. 2008 Oct; 66(9):378-83. . View in PubMed

Effects of dietary salt on renal Na+ transporter subcellular distribution, abundance, and phosphorylation status Am J Physiol Renal Physiol. 2008 Oct; 295(4):F1003-16. . View in PubMed

Connexin 303 is expressed in the kidney but not regulated by dietary salt or high blood pressure. Cell Commun Adhes. 2008 May; 15(1):219-30. . View in PubMed

AMPK activation with AICAR provokes an acute fall in plasma [K+] . 2008 Jan; 294(1):C126-35. . View in PubMed

ANG II provokes acute trafficking of distal tubule Na+-Cl(-) cotransporter to apical membrane Am J Physiol Renal Physiol. 2007 Sep; 293(3):F662-9. . View in PubMed

Evidence for gut factor in K+ homeostasis Am J Physiol Renal Physiol. 2007 Aug; 293(2):F541-7. . View in PubMed

Redistribution of distal tubule Na+-Cl- cotransporter (NCC) in response to a high-salt diet Am J Physiol Renal Physiol. 2006 Aug; 291(2):F503-8. . View in PubMed

Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity Am J Physiol Renal Physiol. 2006 Jun; 290(6):F1543-50. . View in PubMed

Modest dietary K+ restriction provokes insulin resistance of cellular K+ uptake and phosphorylation of renal outer medulla K+ channel without fall in plasma K+ concentration . 2006 May; 290(5):C1355-63. . View in PubMed

Effects of ACE inhibition on proximal tubule sodium transport Am J Physiol Renal Physiol. 2006 Apr; 290(4):F854-63. . View in PubMed

Differential traffic of proximal tubule Na+ transporters during hypertension or PTH: NHE3 to base of microvilli vsNaPi2 to endosomes. Am J Physiol Renal Physiol. 2004 Nov; 287(5):F896-906. . View in PubMed

Dexamethasone treatment causes resistance to insulin-stimulated cellular potassium uptake in the rat . 2004 Nov; 287(5):C1229-37. . View in PubMed

Acute hypotension induced by aortic clamp vsPTH provokes distinct proximal tubule Na+ transporter redistribution patterns. . 2004 Oct; 287(4):R878-85. . View in PubMed

Does membrane trafficking play a role in regulating the sodium/hydrogen exchanger isoform 3 in the proximal tubule? Curr Opin Nephrol Hypertens. 2003 Sep; 12(5):533-41.. View in PubMed

Chronic renal injury-induced hypertension alters renal NHE3 distribution and abundance Am J Physiol Renal Physiol. 2003 May; 284(5):F1056-65. . View in PubMed

Modest K+ restriction provokes insulin resistance of cellular K+ uptake without decrease in plasma K Ann N Y Acad Sci. 2003 Apr; 986:625-7. . View in PubMed

Mechanisms of pressure natriuresis: how blood pressure regulates renal sodium transport Ann N Y Acad Sci. 2003 Apr; 986:669-77. . View in PubMed

Angiotensin II clamp prevents the second step in renal apical NHE3 internalization during acute hypertension Am J Physiol Renal Physiol. 2002 Nov; 283(5):F1142-50. . View in PubMed

Diuretic response to acute hypertension is blunted during angiotensin II clamp . 2002 Oct; 283(4):R837-42. . View in PubMed

Acute hypertension provokes internalization of proximal tubule NHE3 without inhibition of transport activity Am J Physiol Renal Physiol. 2002 Apr; 282(4):F730-40. . View in PubMed

Independent regulation of in vivo insulin action on glucose versus K(+) uptake by dietary fat and K(+) content Diabetes. 2002 Apr; 51(4):915-20. . View in PubMed

Downstream shift in sodium pump activity along the nephron during acute hypertension J Am Soc Nephrol. 2001 Nov; 12(11):2231-40. . View in PubMed

All human Na(+)-K(+)-ATPase alpha-subunit isoforms have a similar affinity for cardiac glycosides . 2001 Oct; 281(4):C1336-43. . View in PubMed

Ouabain and substrate affinities of human Na(+)-K(+)-ATPase alpha(1)beta(1), alpha(2)beta(1), and alpha(3)beta(1) when expressed separately in yeast cells . 2001 Oct; 281(4):C1355-64. . View in PubMed

Glucocorticoids increase sodium pump alpha(2)- and beta(1)-subunit abundance and mRNA in rat skeletal muscle Am J Physiol Cell Physiol. 2001 Mar; 280(3):C509-16. . View in PubMed

Proximal tubule Na transporter responses are the same during acute and chronic hypertension Am J Physiol Renal Physiol. 2000 Aug; 279(2):F358-69. . View in PubMed

Developmental change in Na,K-ATPase alpha1 and beta1 expression in normal and hypothyroid rat renal cortex Am J Nephrol. 2000 May-Jun; 20(3):225-31. . View in PubMed

Molecular mechanisms of sodium transport inhibition in proximal tubule during acute hypertension Curr Opin Nephrol Hypertens. 2000 Mar; 9(2):149-56. . View in PubMed

In vivo PTH provokes apical NHE3 and NaPi2 redistribution and Na-K-ATPase inhibition Am J Physiol. 1999 05; 276(5):F711-9. . View in PubMed

Am J Physiol. 1998 11; 275(5):C1179-81. . View in PubMed

Posttranscriptional upregulation of Na(+)-K(+)-ATPase activity in newborn guinea pig renal cortex Am J Physiol. 1997 Aug; 273(2 Pt 2):F254-63. . View in PubMed

Rapid redistribution and inhibition of renal sodium transporters during acute pressure natriuresis Am J Physiol. 1996 Jun; 270(6 Pt 2):F1004-14. . View in PubMed

Reciprocal regulation of cardiac Na-K-ATPase and Na/Ca exchanger: hypertension, thyroid hormone, development Am J Physiol. 1995 Sep; 269(3 Pt 1):C675-82. . View in PubMed

Expression of Na(+)-K(+)-ATPase alpha- and beta-subunits along rat nephron: isoform specificity and response to hypokalemia Am J Physiol. 1994 Oct; 267(4 Pt 1):C901-8. . View in PubMed

Amiodarone decreases Na,K-ATPase alpha 2 and beta 2 expression specifically in cardiac ventricle J Mol Cell Cardiol. 1994 Apr; 26(4):417-24. . View in PubMed

Nicotine downregulates alpha 2 isoform of Na,K-ATPase at the blood-brain barrier and brain in rats Biochem Biophys Res Commun. 1994 Mar 30; 199(3):1422-7. . View in PubMed

Differential expression of Na,K-ATPase alpha and beta subunit isoforms at the blood-brain barrier and the choroid plexus J Biol Chem. 1993 Apr 15; 268(11):8019-25. . View in PubMed

Na(+)-K(+)-ATPase alpha 1- and beta 1-subunit degradation: evidence for multiple subunit specific rates Am J Physiol. 1993 Mar; 264(3 Pt 1):C583-90. . View in PubMed

Expression of Na,K-ATPase at the blood-brain interface Adv Exp Med Biol. 1993; 331:55-60. . View in PubMed

Physiologic rationale for multiple sodium pump isoformsDifferential regulation of alpha 1 vs alpha 2 by ionic stimuli. Ann N Y Acad Sci. 1992 Nov 30; 671:156-68; discussion 168-9. . View in PubMed

Low K+ increases Na(+)-K(+)-ATPase alpha- and beta-subunit mRNA and protein abundance in cultured renal proximal tubule cells Am J Physiol. 1992 Aug; 263(2 Pt 1):C436-42. . View in PubMed

Differential regulation of sodium pump isoforms in heart Semin Nephrol. 1992 Jan; 12(1):49-55. . View in PubMed

Rapid hypertensinogenic effect of lead: studies in the spontaneously hypertensive rat Toxicol Ind Health. 1992 Jan-Apr; 8(1-2):89-102. . View in PubMed

Hypokalemia decreases Na(+)-K(+)-ATPase alpha 2- but not alpha 1-isoform abundance in heart, muscle, and brain Am J Physiol. 1991 May; 260(5 Pt 1):C958-64. . View in PubMed

Low K+ increases Na,K-ATPase abundance in LLC-PK1/Cl4 cells by differentially increasing beta, and not alpha, subunit mRNA J Biol Chem. 1990 Oct 15; 265(29):17935-40. . View in PubMed

Differential regulation of Na,K-ATPase alpha 1, alpha 2, and beta subunit mRNA and protein levels by thyroid hormone J Biol Chem. 1990 Aug 25; 265(24):14308-14. . View in PubMed

Ionic regulation of the biosynthesis of NaK-ATPase subunits Semin Nephrol. 1990 Jul; 10(4):400-9. . View in PubMed

alar4, a constitutive mutant of the A system for amino acid transport, has increased abundance of the Na+,K+-ATPase and mRNA for alpha 1 subunit of this enzyme Proc Natl Acad Sci U S A. 1989 Oct; 86(20):7984-8. . View in PubMed

Patterns of mRNA expression during early cell growth differ in kidney epithelial cells destined to undergo compensatory hypertrophy versus regenerative hyperplasia Proc Natl Acad Sci U S A. 1988 Sep; 85(18):6768-72. . View in PubMed

Isozymes of dog heart Na+-K+-ATPase are immunologically similar to isozymes in brain Am J Physiol. 1987 Dec; 253(6 Pt 1):C862-5. . View in PubMed

Enrichment of Na+-Ca2+ exchange in cardiac sarcolemmal vesicles by alkaline extraction Biochim Biophys Acta. 1987 May 12; 899(1):59-66. . View in PubMed

Molecular cloning and sequence analysis of the (Na+ + K+)-ATPase beta subunit from dog kidney Biochim Biophys Acta. 1987 Apr 08; 912(2):244-53. . View in PubMed

Pretranslational regulation of Na-K-ATPase in cultured canine kidney cells by low K+ Am J Physiol. 1987 Feb; 252(2 Pt 1):C179-89. . View in PubMed

Developmental and thyroid hormone regulation of two molecular forms of Na+-K+-ATPase in brain J Biol Chem. 1986 Aug 05; 261(22):10439-44. . View in PubMed

Isolation of partial cDNAs for rat liver and muscle glycogen phosphorylase isozymes FEBS Lett. 1986 Jul 07; 202(2):282-8. . View in PubMed

Mapping subcellular distribution of Na+-K+-ATPase in rat parotid gland Am J Physiol. 1986 Mar; 250(3 Pt 1):C430-41. . View in PubMed

Immunodetection of Na,K-ATPase in guinea-pig retinal layers, cornea and lens Exp Eye Res. 1985 May; 40(5):667-74. . View in PubMed

Comparison of subunits of cardiac, brain, and kidney Na+-K+-ATPase Am J Physiol. 1985 Mar; 248(3 Pt 1):C247-51. . View in PubMed

Assembly of the (Na+ + K+)-adenosine triphosphatasePost-translational membrane integration of the alpha subunit. J Biol Chem. 1984 Feb 25; 259(4):2629-35. . View in PubMed

Characteristics of antibodies to guinea pig (Na+ + K+)-adenosine triphosphatase and their use in cell-free synthesis studies J Membr Biol. 1982; 69(1):13-22. . View in PubMed

Hana kai ii: a 17-day dry saturation dive at 186 ATA. III. Body fluid balance. Undersea Biomed Res. 1977 Sep; 4(3):247-65. . View in PubMed

Alicia McDonough, PhD, FAHA, is a research scientist in the field of cardiorenal physiology and hypertension. The McDonough lab’s basic and translational approaches have been driven by challenging our understanding of the molecular mechanisms responsible for the maintenance of electrolyte homeostasis and control of blood pressure in the human body. Her contributions are represented by more than 130 peer reviewed scientific studies.

Currently a Professor of Physiology and Neurosciences, Keck School of Medicine of USC in Los Angeles, CA, she earned degrees in Physiology at UC Berkeley (AB) and at the University of Hawaii (PhD), and was trained in molecular Physiology at UC San Francisco Cardiovascular Research Institute and Columbia University. She joined USC in 1981 where she became Professor in 1996. Initially, her lab focused on regulation of the biosynthesis and assembly of sodium pump subunits and molecular mechanisms controlling sodium pump isoforms in kidney, cardiac and skeletal muscle by potassium, hormones, and other factors under normal conditions and during human heart failure. Building on these findings, the lab addressed the coordinated and concerted control of extracellular potassium by skeletal muscle, kidney and gut in response to altered metabolic and electrolyte demands and have begun to use these findings to address the mechanisms responsible for the cardiovascular benefit of raising dietary K/Na ratio.

The McDonough laboratory has especially focused on renal mechanisms responsible for regulation of sodium and potassium balance as well as blood pressure. They discovered that changes in blood pressure, or alterations in Angiotensin II, provoke rapid trafficking of renal sodium transporters between membrane domains, associated with phosphorylation and pool size regulation. Using the transporter profiling approach, Dr. McDonough and her colleagues have defined how stimuli such as dietary salts, Ang II, kidney injury, and immune cytokines increase renal sodium transport in a region specific manner along the nephron and how resultant hypertension provokes intrarenal responses to decrease sodium reabsorption (via pressure natriuresis), a response that defines the blood pressure set point in the kidney. Additionally, they are using this approach to investigate sexual dimorphisms in the female vs. male nephron and what the dimorphisms reveal about the cardiovascular disease protection evident in females. These projects have engaged the McDonough lab with expert collaborators across the USA and around the world and attracted attention to the important role of the kidney in balancing the intertwined homeostasis of sodium, potassium and blood pressure.

Dr. McDonough is a recipient of multiple Awards including an American Heart Association (AHA) Established Investigator Award (1984), the 2009 Starling Distinguished Lectureship from the American Physiological Society (APS), the 2014 Donald Seldin Lectureship from the AHA Council on the Kidney in Cardiovascular Disease (KCVD), the Robert Schrier Lecture at ASN Kidney week (2017), and the Steven Hebert (APS, 2018). She has delivered the 2010 Suk Ki Hong Memorial Lecture at SUNY Buffalo, the 2015 Rudy Clarenberg Distinguished Lecture at Kansas State University, the J.J. Smith Memorial Lecture at Medical College of Wisconsin, the keynote lecture at the Annual Young Investigator Symposium during American Society of Nephrology (ASN) Kidney Week (2016) and the Ulrich Hopfer Lectureship, Case Western Reserve University School of Medicine. Alicia McDonough is highly committed to service to the research community. She actively contributes to APS, AHA and ASN committees, grant reviews and editorial boards. She also served on multiple study sections for NIH, VA, AHA and other national and international agencies. Importantly, she has demonstrated commitment to training and mentoring the next generation of medical and PhD students, postdoctoral fellows and junior faculty.
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