Alicia A. McDonough Professor Physiology & Biophysics Keck School of Medicine

Education:
AB 1972 Physiology- University of California, Berkeley
PhD 1977 Physiology- University of Hawaii, Manoa

Postdoctoral Research Fellowship:
1978 University of California, San Francisco
1978-1981 Columbia University, New York

Started at USC: 1981

Research Topics: Membranes & Transport, Cardiovascular & Skeletal Muscle Diseases, Diabetes/Metabolic Diseases, Endocrinology/Metabolism, Physiology

Research Description

The overall theme of the McDonough lab is to understand the molecular mechanisms responsible for homeostatic control of extracellular Na+, volume, blood pressure and K+, how these are disrupted in disease states and can be corrected therapeutically. Current programs include:

1) Hypertension: Renal sodium transport can compensate for hypertension if decreased or cause hypertension if elevated. Our current aim is to understand the mechanisms and signals responsible for the changes in sodium transport that occur during hypertension, the molecular mechanisms responsible for the blood pressure lowering effects of anti-hypertensive inhibitors of the renin angiotensin system, and to dissect the molecular mechanisms responsible for renal injury neurogenic dependent hypertension. We pursue these studies in both normotensive and hypertensive animal models applying multi-level strategies from whole animal measures of blood pressure and renal function to biochemical analyses of transporter pool size and subcellular distribution, to confocal and electron microscopy analysis of ion transporter trafficking, to proteomic analyses of transporter associated proteins.

2) Extrarenal mechanisms to regulate K+ homeostasis: The overall aims of this line of investigation are to determine the molecular mechanisms responsible for maintaining extracellular K+ in a narrow range through the concerted regulatory responses of the kidney and muscle. We are interested in determining how muscle K+ stores are tapped during hypokalemia, how excess plasma [K+] is cleared into the ICF store in hyperkalemia and during exercise and after K+ restoration, and to understand how these processes are altered in a set of clinically relevant paradigms such as diuretic use and steroid treatment. We have discovered a novel variety of insulin resistance to K+ uptake that occurs during low K+ states, and a novel pathway to clear K+ to the ICF during high K+ states. In addition, we are interested in determining the K+ sensor that sets of regulatory adjustments.

Selected Publications

Petrovic S, Barone S, Wang Z, McDonough AA, Amlal H, Soleimani M. - Slc26a6 (PAT1) Deletion Downregulates the Apical Na/H(+) Exchanger in the Straight Segment of the Proximal Tubule. - Am J Nephrol [ 2007 ] Nov 29;28(2):330-338 . PubMed

Zheng D, Perianayagam A, Lee DH, Brannan MD, Yang LE, Tellalian D, Chen P, Lemieux K, Marette A, Youn JH, McDonough AA. - AMPK Activation with AICAR Provokes an Acute Fall in Plasma [K+]. - Am J Physiol Cell Physiol [ 2007 ] Nov 14; . PubMed

Yang LE, Leong PK, McDonough AA. - Reducing blood pressure in SHR with enalapril provokes redistribution of NHE3, NaPi2, and NCC and decreases NaPi2 and ACE abundance. - Am J Physiol Renal Physiol [ 2007 ] Oct;293(4):F1197-208 . PubMed

Lee FN, Oh G, McDonough AA, Youn JH. - Evidence for gut factor in K+ homeostasis. - Am J Physiol Renal Physiol [ 2007 ] Aug;293(2):F541-7 . PubMed

Sandberg MB, Riquier AD, Pihakaski-Maunsbach K, McDonough AA, Maunsbach AB. - 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 . PubMed

Elitsur N, Lorenz JN, Hawkins JA, Rudolph JA, Witte D, Yang LE, McDonough AA, Cohen MB. - The proximal convoluted tubule is a target for the uroguanylin-regulated natriuretic response. - J Pediatr Gastroenterol Nutr [ 2006 ] Jul;43 Suppl 1:S74-81 . PubMed

Sandberg MB, Maunsbach AB, McDonough AA. - 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 . PubMed

Leong PK, Yang LE, Landon CS, McDonough AA, Yip KP. - Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity. - Am J Physiol Renal Physiol [ 2006 ] Jun;290(6):F1543-50 . PubMed

Chen P, Guzman JP, Leong PK, Yang LE, Perianayagam A, Babilonia E, Ho JS, Youn JH, Wang WH, McDonough AA. - 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. - Am J Physiol Cell Physiol [ 2006 ] May;290(5):C1355-63 . PubMed

Leong PK, Devillez A, Sandberg MB, Yang LE, Yip DK, Klein JB, McDonough AA. - Effects of ACE inhibition on proximal tubule sodium transport. - Am J Physiol Renal Physiol [ 2006 ] Apr;290(4):F854-63 . PubMed