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Rockville, Md. (September 25, 2019)—International physiologists and researchers studying the kidney, high blood pressure and related medical conditions will convene next week at the American Physiological Society (APS) Aldosterone and ENaC in Health and Disease: The Kidney and Beyond Conference in Estes Park, Colo.

The number of people with obesity, age-related high blood pressure and heart failure is steadily increasing. The rise in these chronic health conditions highlights the importance of understanding the drivers of heart disease, including aldosterone—a mineralocorticoid hormone produced by the adrenal glands—and its relationship with the epithelial sodium channel (ENaC) and mineralocorticoid receptor (MR). ENaC is an ion channel located on cell membranes that forms a pathway for sodium reabsorption in the kidneys. MR is a protein that binds to aldosterone, an important regulator of ENaC. Together, they regulate the body’s balance of salt and water.

“Elevated aldosterone and activation of mineralocorticoid receptors is increasingly common in growing populations with heart failure, high blood pressure and obesity. In these populations, elevated aldosterone is associated with increased risk of heart attack, stroke and cardiovascular death,” said conference co-organizer Iris Jaffe, MD, PhD, of Tufts Medical Center in Boston. “This conference summarizes state-of-the-art understanding of the mechanisms driving inappropriate aldosterone release and [its] impact on the heart, lung, kidneys, blood vessels and [other organs],” Jaffe said.

“It brings together scientists from two complementary fields (aldosterone/MR and ENaC) and from across the spectrum of basic to clinical research. In this way, the conference facilitates synergies and new interactions that advance the research in these fields,” added conference co-organizer Peter Snyder, MD, of the University of Iowa.

Topics “will cover new and exciting discoveries in ENaC [such as] the recently solved three-dimension structure of ENaC and the development of mini kidneys (kidney organoids) for clinical research” said conference co-organizer Daniela Rotin, PhD, of the Hospital for Sick Children and University of Toronto in Canada.

Conference goals include learning more about the basic biology of these molecules, their role in kidney function and blood pressure, and the patients who would benefit most from emerging treatments. The program will include research-based sessions, abstract-driven presentations and poster sessions.

Program Highlights

Wednesday, October 2
Keynote Lecture: Human kidney organoids
Chair: Daniela Rotin, PhD, Hospital for Sick Children and University of Toronto, Canada
Speaker: Joseph Bonventre, MD, PhD, Harvard University, Cambridge, Mass.

Thursday, October 3
Symposium 1A: Aldosterone and mineralocorticoid receptors in the kidney and hypertension
Chairs: David Calhoun, MD, University of Alabama, Birmingham; Celso Gomez-Sanchez, MD, University of Mississippi

Speakers:
“MR activation by Rac1 in kidney disease”
Toshiro Fujita, MD, PhD, University of Tokyo, Japan

“The expanding spectrum of primary aldosteronism”
Anand Vaidya, MD, Brigham and Women’s Hospital and Harvard Medical School, Boston

“The intercalated cell mineralocorticoid receptor regulates pendrin directly and regulates principal cell ENaC indirectly over a wide range in serum K+”
Susan Wall, MD, Emory University, Atlanta

“Kir5.1-mediated changes in renin-angiotensin-aldosterone system balance in salt sensitive hypertension”
Anna Manis, Medical College of Wisconsin

“A proof-of-principle study of sodium loading in prehypertension”
J. Brian Byrd, MD, University of Michigan Medical School

Symposium 1B: Metabolic and sex differences in aldosterone responses
Chairs: Massi Caprio, MD, PhD, Istituto di Ricerca e Cura a Catterere Scientifico (IRCCS), Italy; James Luther, MD, Vanderbilt University, Nashville, Tenn.

Speakers:
“Biological sex-specific differences in the aldosterone responses to angiotensin II in humans and rodents”
Jose Romero, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston

“The Leptin-aldosterone-mineralocorticoid receptor axis: a major contributor to cardiovascular disease in obese females”
Eric Belin de Chantemèle, PhD, Augusta University, Georgia

“Hypersensitivity of renal ENaC to aldosterone is a sex-specific determinant of blood pressure control in females”
Mykola Mamenko, PhD, Augusta University, Georgia

“Female mice exhibit higher increases in aldosterone synthase expression and aldosterone production than males in response to low-salt diet”
Jessica Faulkner, PhD, Medical College of Georgia at Augusta University

Symposium 2A: Structure function of ENaC and related transporters
Chairs: Peter Snyder, MD, University of Iowa; Bernard Rossier, MD, University of Lausanne, Switzerland

Speakers:
“ENaC structure by cryo-electron microscopy”
Isabelle Baconguis, PhD, Oregon Health and Science University

“ENaC gating regulation by biliary factors”
Ossama Kashlan, PhD, University of Pittsburgh

“ENaC subunit N-glycans have different roles for the ability of the channel to respond to shear force”
Martin Fronius, PhD, University of Otago, New Zealand

“N-methyl-D-aspartate (NMDA) receptor interacts with ENaC to induce renal vasodilation in the connecting tubule”
Cesar Romero, PhD, Emory University School of Medicine, Atlanta

“Proton block of the epithelial sodium channel”
Daniel Collier, PhD, University of Tennessee Health Science Center

Symposium 2B: ENaC function and regulation in tissues
Chairs: Lawrence Palmer, PhD, Cornell University, New York; Edith Hummler, PhD, University of Lausanne, Switzerland

Speakers:
“Regulation of ENaC by extracellular Na”
Thomas Kleyman, MD, University of Pittsburgh

“ENaC Regulation by aldosterone and proteases”
Christoph Korbmacher, MD, Friedrich-Alexander University of Erlangen-Nürnberg, Germany

“Potassium sensing in the distal nephron”
David Penton Ribas, PhD, University of Zurich, Switzerland

“The hypertension pandemic: an evolutionary perspective”
Bernard Rossier, MD, University of Lausanne, Switzerland

Friday, October 4
Symposium 3A: Signaling and regulation of ENaC and other epithelial channels/transporters I
Chair: Doug Eaton, PhD, Emory University, Atlanta

Speakers:
“ENaC regulation by the mTORC2-SGK1 signaling module”
David Pearce, MD, University of California, San Francisco

“Role of microRNAs in aldosterone signaling and ENaC regulation”
Michael Butterworth, PhD, University of Pittsburgh

“AMPK regulates ENaC via a tripartite inhibitory complex”
Kenneth Hallows, MD, PhD, University of Southern California

“Elevated sodium activates the NLRP3 inflammasome in antigen presenting cells through an ENaC-dependent mechanism”
Ashley Pitzer, PhD, Vanderbilt University Medical Center, Nashville, Tenn.

“Postprandial effects on ENaC-mediated sodium absorption”
Christine Klemens, PhD, Medical College of Wisconsin

Symposium 3B: Signaling and regulation of ENaC and other epithelial channels/transporters II
Chairs: Alexander Staruschenko, PhD, Medical College of Wisconsin; Jim Stockand, PhD, University of Texas, San Antonio

Speakers:
“WNK kinases and cell volume regulation”
Arohan Subramanya, MD, University of Pittsburgh

“From SPLUNC1 to SPX-101, novel peptidomimetics to treat sodium hyperabsorption in the CF lung”
Robert Tarran, PhD, University of North Carolina

“Direct effect of potassium on ENaC regulation and potassium secretion in collecting duct cells: role of mTORC2/SGK1 signaling”
Bidisha Saha, PhD, University of California, San Francisco

“High mobility group box-1 protein regulates lung epithelial sodium channel activity via the receptor for advanced glycation end products”
Garett Grant, University of Utah

Symposium 4A: ENaC biogenesis and trafficking
Chair: Daniela Rotin, PhD, Hospital for Sick Children and University of Toronto, Canada

Speakers:
“Novel mechanisms of diuretic resistance revealed by single cell analysis”
Vivek Bhalla, MD, Stanford University School of Medicine, California

“Regulation of renal ion transport by ubiquitylation and phosphorylation networks”
Olivier Staub, PhD, University of Lausanne, Switzerland

“Regulation of ENaC by the ER lumenal, molecular chaperone, GRP170”
Teresa Buck, PhD, University of Pittsburgh

“A conserved region in the N-terminus of alpha-ENaC regulates proteolytic processing during anterograde transport”
Pradeep Kota, PhD, University of North Carolina at Chapel Hill

Saturday, October 5
Symposium 5A: MR in the vasculature
Chairs: Frederic Jaisser, MD, PhD, Institut Nationale de la Santé et de la Recherche Médicale (INSERM), France; Iris Jaffe, MD, PhD, Tufts Medical Center, Boston

Speakers:
“Sex-specific mechanisms of resistance vessel endothelial dysfunction in obesity”
Ana Davel, PhD, University of Campinas, Brazil

“Sex differences in the role of the smooth muscle cell mineralocorticoid receptor in cardiovascular aging”
Jennifer DuPont, PhD, Tufts Medical Center, Boston

“Role of the myeloid mineralocorticoid receptor in vascular inflammation in atherosclerosis”
Joshua Man, Tufts Medical Center, Boston

“Aldosterone and angiotensin II increase aortic stiffness and endothelial dysfunction via an action of oxidative stress on the endothelial sodium channel”
James Sowers, MD, University of Missouri

“The novel non-steroidal MR antagonist finerenone improves metabolic parameters via ATGL-mediated lipolysis of brown adipose tissue in high-fat diet fed mice”
Vincenzo Marzolla, PhD, IRCCS, Italy

Symposium 5B: MR structure and role in the heart and lungs
Chairs: Gail Adler, MD, PhD, Brigham and Women’s Hospital, Boston; Shawn Bender, PhD, University of Missouri

Speakers:
“Enhanced endothelium epithelial sodium channel signaling prompts left ventricular diastolic dysfunction in obese female mice”
Guanghong Jia, PhD, University of Missouri School of Medicine

“Structural determinants of activation of the mineralocorticoid receptor: an evolutionary perspective”
Peter Fuller, MD, PhD, Hudson Institute of Medical Research, Australia

“The quaternary structure of the mineralocorticoid receptor depends on ligand and DNA binding”
Diego Alvarez de la Rosa, PhD, Universidad de La Laguna, Spain

“Vascular cell-specific roles of mineralocorticoid receptors in pulmonary hypertension”
Ioana Preston, MD, Tufts Medical Center, Boston

Clinical Plenary Lecture
Chair: Maria-Christina Zennaro, MD, PhD, Paris Cardiovascular Research Center, France

Speaker:
“The role of non-steroidal MR antagonists and new potassium binders for the treatment of cardiovascular disease”
Bertram Pitt, MD, University of Michigan

Sunday, October 6
Symposium 6A: Normal and pathogenic regulation of aldosterone biosynthesis
Chairs: Eleanor Davies, PhD, University of Glasgow, Scotland; Jun Yang, PhD, Monash University, Australia

Speakers:
“Development of an inducible mouse model of aldosteronism”
William Rainey, PhD, University of Michigan

“A gain of function mutation in CLCN2 chloride channel gene causes primary aldosteronism”
Fabio Fernandes-Rosa, PhD, INSERM U970, France

“Circulating microRNAs as diagnostic biomarkers of primary aldosteronism”
Eleanor Davies, PhD, University of Glasgow, Scotland

“The retinoic acid receptor a contributes to the development of primary aldosteronism by regulating adrenal cortex structure through interactions with Wnt and Vegfa signaling”
Sheerazed Boulkroun, PhD, INSERM U970, France

Symposium 6B: Integrated regulation of renal ion transport
Chairs: David Ellison, MD, Oregon Health Science University; Johannes Loffing, MD, University of Zurich, Switzerland

Speakers:
“The role of ENaC in hyperoxia-induced preterm lung injury”
My Helms, PhD, University of Utah

“Regulation of renal ion transport and blood pressure by the CRL3-WNK-SPAK pathway”
James McCormick, PhD, Oregon Health and Science University

“WNK regulation of ion transport in the malpighian tubule”
Aylin Rodan, PhD, University of Utah

“Interleukin 6 activation of the epithelial sodium channel in the distal convoluted tubule and cortical collecting duct via Rac1”
Oishi Paul, Emory University, Atlanta

NOTE TO JOURNALISTS: The APS Aldosterone and ENaC in Health and Disease: The Kidney and Beyond Conference will be held October 2–6 in Estes Park, Colo. To schedule an interview with the conference organizers or presenters, contact the APS Communications Office or call 301.634.7314. Find more research highlights in the APS News Room.

Physiology is the study of how molecules, cells, tissues and organs function in health and disease. Established in 1887, the American Physiological Society (APS) was the first U.S. society in the biomedical sciences field. The Society represents more than 10,000 members and publishes 15 peer-reviewed journals with a worldwide readership.

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