Anjaparavanda P. Naren, PhD

Thomas Boat Chair in Cystic Fibrosis Research

Co-Director, Cystic Fibrosis Research Center

Professor, UC Department of Pediatrics

Phone 513-803-4731

Email anaren@cchmc.org

Cystic fibrosis; secretory diarrhea.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a cAMP-regulated chloride channel located primarily on the apical surface of epithelial cells that line various organs, including the airways and the gut. CFTR dysfunction is detrimental and may result in life-threatening medical disorders. Dr. Naren's laboratory studies two such disorders; (1) Cystic fibrosis, a lethal genetic disease that affects mostly the Caucasian population (>30,000 in USA), in which the CFTR chloride channel is HYPO-functional and (2) Secretory diarrhea, a disease affecting millions of children worldwide, in which HYPER-function of the CFTR chloride channel can occur due to infectious toxins, such as Cholera toxin and E. coli enterotoxin. His lab is interested in identifying interactions between CFTR and its binding partners and defining how spatiotemporal regulation of CFTR-containing macromolecular complexes in the apical compartment of polarized epithelial cells lining the secretory epithelia regulates overall fluid secretion. Our studies will identify new drug targets for cystic fibrosis, secretory diarrhea, and other diseases resulting from CFTR dysfunction and provide insights into the etiology of diseases associated with CFTR-interacting molecules.

PhD: Biochemistry, Indian Institute of Science, Bangalore, India, 1993.

Ren A, Zhang W, Sunitha Y, Arora K, Sinha C, Moon CS, Naren AP. MAST205 Competes with CAL for Binding to CFTR to Regulate CFTR-mediated Fluid Transport. J Biol Chem. 2013 April:26;288(17):12325-34.

Yarlagadda S, Zhang W, Penmatsa H, Ren A, Arora K, Naren AP*, Khan FA, Donnellan C, Srinivasan S, Stokes D, Kappes JC. A Young Hispanic with c.1646G>A Mutation Exhibits Severe Cystic Fibrosis Lung Disease: Is Ivacaftor an Option for Therapy? Am J Respir Crit Care Med. 2012 Oct:1 186(7):694-6. (*Corresponding Author)

Zhang  W, Penmatsa H, Ren A, Punchihewa C, Lemoff A, Yan B, Fujii N, Naren AP. Functional regulation of CFTR-containing macromolecular complexes: a small-molecule inhibitor approach. Biochem J. 2011 April:15;435(2):451–62

Penmatsa H, Zhang W, Yarlagadda S, Li C, Conoley VG, Yue J, Bahouth SW, Buddington RK, Zhang G, Nelson DJ, Sonecha MD, Manganiella V, Wine JJ, Naren AP. Compartmentalized cyclic adenosine 3’,5’-monophosphate at the plasma membrane clusters PDE3A and cystic Fibrosis transmembrane conductance regulator into microdomains. Mol Biol Cell. 2010 Mar:15;21:1097-110.

Li C, Krishnamurthy PC, Penmatsa H, Marrs KL, Wang XQ, Zaccolo M, Jalink K, Li M, Nelson DJ, Schuetz JD, Naren AP. Spatiotemporal Coupling of cAMP Transporter to CFTR Chloride Channel Function in the Gut Epithelia. Cell. 2007 Nov:30;131(5): 940-51.

Li C, Dandridge KS, Di A, Marrs KL, Harris EL, Roy K, Jackson JS, Makarova NV, Fujiwara Y, Farrar, PL, Nelson DJ, Tigyi GJ, Naren AP. Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactionsJ Exp Med. 2005 Oct:3; 202(7):975-86.

Naren AP, Cobb B, Li C, Roy K, Nelson D, Heda GD, Liao J, Kirk KL, Sorscher EJ, Hanrahan J, Clancy JP. A macromolecular complex of beta 2 adrenergic receptor, CFTR, and ezrin/radixin/moesin-binding phosphoprotein 50 is regulated by PKA. Proc Natl Acad Sci USA. 2003 Jan:7;100(1):342-46.

Naren AP, Anke D, Cormet-Boyaka E, Boyaka PN, McGhee JR, Zhou W,  Akagawa K, Fujiwara T, Thome U, Engelhardt JF, Nelson DJ, Kirk KL. Syntaxin 1A is expressed in airway epithelial cells, where it modulates CFTR Cl(-) currents. J Clin Invest.  2000 Feb;105(3):377-86.

Naren AP, Cormet-Boyaka E, Fu J, Villain M, Blalock E, Quick MW, Kirk KL. CFTR Chloride channel regulation by an interdomain interaction. Science. 1999 Oct:15;286(5439):544-8.

Naren AP, Nelson DJ, Xie W, Jovov B, Tousson A, Pevsner J, Bennett MK, Benos DJ, Quick MW, Kirk KL. Regulation of CFTR chloride channels by syntaxin and Munc18 isoforms. Nature. 1997 Nov:20;390(6657):302-5.

LPA2-receptor containing complexes in regulating secretory diarrhea. Principal Investigator. National Institutes of Health. July 2011 - June 2015. DK093045.

Inhibition of a cAMP transporter (MRP4) in the gut induces diarrheaPrincipal Investigator. National Institutes of Health. June 2009 - Apr 2018. DK080834.

Using mouse Intestinal Stem Cells (ISC) to study CTFR correctors and/or potentiators. Principal Investigator. Vetex-Concept Award. Oct 2013 - Sep 2014.