Education

Research Interest

Cystic fibrosis transmembrane conductance regulator (CFTR) has been implicated in several diseases. The most lethal being Cystic Fibrosis, a genetic disease affecting largely the Caucasian population in the U.S. Our recent work has been involved in understanding the structural and functional aspects of CFTR Cl¯ ion channel biology. Our laboratory deals with 3 major projects, which are:

1. Exploring the therapeutic potential of some of the reagents we have developed to augment the Cl¯ current activity of partial loss of function CFTR mutants.
2. To understand the physical and functional coupling of the channel (CFTR) to the receptor (beta 2AR and LPA2) and its relevance to CFTR-dysfunction diseases.
3. To Define a role for CFTR and t-SNARE (syntaxin 1A and SNAP23) interaction in vesicular translocation.

Research Support

American Lung Association, 07-01-2005 to 06-30-2008
(Career Investigator Award)
Cooperative regulation of MRP 2 and CFTR in lung epithelial cells
Principal Investigator: A. P. Naren

R01 (R01-DK55532) 01-01-2004 to 12-31-08
Intestinal Mucosal Protection by Epidermal Growth Factor
(Principal Investigator: R.K. Rao) Co-Investigator: A.P. Naren

RO-3 (NIH-NIAID)  04-1-07 to 03-31-09
?V. cholerae as a bioterror agent: New means of treating a potential pandemic?.
Principal Investigator: A. P. Naren

R0-1(DK-74996) 04-01-2006 to 03-31-2010
CFTR-dependent protein interactions regulate diarrhea
Principal Investigator: A.P. Naren

R01 (AA 12307-06) 07-01-2005 to 12-31-2010
Mechanism of endotoxin absorption in alcoholism
(Principal Investigator:  R. K. Rao)
Co-Investigator: A. P. Naren

Selected Publications

Li, C., Krishnamurthy, P.C., Penmatsa, H., Marrs, K. L. Wang, X. Q., Zaccolo, M., Jalink, K., Li, M., Nelson, D. J. Schuetz, J. D. and Naren, A. P (2007). Spatiotemporal Coupling of cAMP Transporter to CFTR Chloride Channel Function in the Gut Epithelia. Cell 131: 940-951.

Gardner, L., Naren, A. P and Bahouth, S (2007) Assembly of a SAP97-AKAP79-PKA scaffold at the type-1 PDZ motif of the human beta1-adrenergic receptor generates a receptosome involved in receptor recycling and networking J. Biol. Chem. 282: 5085-5099

Di, A., Brown, M. E., Deriy, L. V., Li, C., Chen, Y., Huang, P., Tong, J., Naren, A. P., Palfrey, H. C., Bindokas, V and Nelson. D.J. (2006) CFTR controls elimination of phagocytosed bacteria in macrophages. Nature-Cell Biology 8:933-944

Basuroy, S., Seth, A., Elias, B., Naren, A. P. and Rao, R. (2006) MAP kinase interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide. Biochem. J. 393:69-77

Li, C., Dandridge K. S., Di, A., Marrs, K. L., Harris, E. L., Roy, K., Jackson, J. S., Makarova, N. V., Fujiwara, Y., Farrar, P.L., Nelson, D. J., Tigyi, G. J and Naren, A. P. (2005) Lysophosphatidic acid inhibits cholera toxin-induced secretory diarrhea through CFTR-dependent protein interactions. J. Exp. Med. 202:975-986

Li, C., and Naren, A. P. (2005) Macromolecular complexes of cystic fibrosis transmembrane conductance regulator and its interacting partners. Pharmacology and Theraputics 108: 208-223

Fu, J., Naren, A. P., Gao, X., Ahmmed, G. U., Malik, A. B (2005) PAR-1 activation of endothelial cells induces PKCalpha -dependent phosphorylation of syntaxin 4 and Munc18c. Role in signaling P-selectin expression. J. Biol. Chem. 280: 3178-3184.

Li, C., Roy, K., Dandridge, K and Naren, A. P. (2004) Molecular assembly of cystic fibrosis transmembrane conductance regulator in plasma membrane. J. Biol. Chem. 279: 24673-24684.

Naren, A. P., Cobb, B., Li, C., Roy, K., Nelson, D., Heda, G. D., Liao, J., Kirk, K.L Sorscher, E.J., Hanrahan, J. and Clancy, J.P. (2003) A macromolecular complex of beta2AR, CFTR and EBP50 is regulated by protein kinase A. Proc. Natl. Acad. Sci. USA. 100: 342-346.

Cormet-Boyaka, E., Di, A., Naren, A. P., Nelson, D.J. and Kirk K.L. (2002) CFTR chloride channel are regulated by a SNAP23/syntaxin 1A complex. Proc. Natl. Acad. Sci. USA. 101: 8221-8226.

Di, A., Krupa, B., Chen, Y., Naren, A. P., Kirk, K, L. Nelson, D.J.(2002)          Quantal Release of Free Radicals Correlated with Exocytosis of Phagosomes. Nature Cell Biol. 4: 279-285.

Chang. S. Y., Di, A., Naren, A. P., Kirk, K.L., Palfrey, H.C. and Nelson,     D.J. (2002). Mechanism of CFTR regulation by syntaxin 1A and PKA.  J. Cell. Sci 115:783-791.

Fu, J., Ji, H-L., Naren, A. P. and Kirk, K.L. (2001) A cluster of negative charges at the amino terminal tail of CFTR regulates ATP dependent channel gating.  J. Physiol. (London). 536: 459-470.

Naren, A. P. and Kirk, K.L. (2000) CFTR Cl- channels and regulatory networks. News in Physiol. Sci. 15: 57-61.

Naren, A. P., Anke, D., Cormet-Boyaka, E., Boyaka, P. N., McGhee,J. R., Zhou,W.,   Akagawa, K., Fujiwara, T., Thome,U.,  Engelhardt, J.F., Nelson, D. J. and Kirk,K.L.(2000) Syntaxin 1A is Expressed in Airway Epithelial Cells Where it Modulates CFTR Cl- Currents. J. Clin. Invest. 105: 377-386.

Naren, A. P., Cormet-Boyaka. E., Fu, J., Villain, M., Blalock, E., Quick M.W., and Kirk, K.L.  (1999) CFTR Chloride channel regulation by an interdomain interaction. Science. 286: 544-548.

Tousson, A., Van Tine, B.A., Naren, A. P., Shaw, G.M. and Schwiebert, L.M. (1998) Characterization of CFTR expression and chloride channel activity in human endothelia. Am. J. Physiol. 275: C1555-C1564.

Naren, A. P., Quick M.W., Collawn, J.F., Nelson, D.J. and Kirk, K.L. (1998) Syntaxin 1A directly inhibits CFTR chloride channel by means of  domain-specific interactions. Proc. Natl. Acad. Sci. USA 95: 10972-10977.

Naren, A. P., Nelson, D.J., Xie, W., Jovov, B., Tousson, A., Pevsner, J., Bennett, M. K., Benos, D.J. Quick, M.W., and Kirk, K.L. (1997) Regulation of CFTR chloride channels by syntaxin and Munc 18 isoforms. Nature 390: 302-305