Regulation of mucin secretion and nucleotide release in airway epithelial cells. Targeting of therapeutic molecules to the airway epithelium.
Dr. Kreda’s research focusses in identifying signaling molecules/pathways that regulate airway mucin secretion. The main goal is to uncover potential targets of clinical interest to control abnormal lumenal mucus accumulation in lung diseases. Her lab has developed and optimized in vitro and in vivo models of lung diseases and quantitative assays for therapeutic drug testing and evaluation of mucin production in airway epithelia.
Dr. Kreda’s lab also studies mechanisms of molecule uptake in the airway epithelia. The main goal is to develop novel and efficacious delivery strategies of therapeutic agents and nucleic acids in obstructive lung diseases.
Funding sources for Dr. Kreda’s lab include Cystic Fibrosis Foundation, National Institutes of Health (NIH), NCTraCS (the NIH CTSA at UNC-CH), AstraZeneca, and Forest Research Institute (now AstraZeneca).
Her lab has successful collaborations with scientists from academic and pharmaceutical institutions to develop and test novel drugs for their potential therapeutic use in obstructive lung diseases. For more information contact Dr. Kreda.
- 1992 Post Doctorate, University of North Carolina at Chapel Hill
- 1992 Ph.D., University of Buenos Aires, Argentina
- 1987 M.S., University of Buenos Aires, Argentina
- 1986 Pharm D., R.Ph., University of Buenos Aires, Argentina
- 1984 B.S., University of Buenos Aires, Argentina
- Silvia M. Kreda holds an Associate Professor appointment in the Department of Medicine and is a faculty member of the Marsico Lung Institute/Cystic Fibrosis Center.
- Agramunt, J; Pedroso, E; Kreda, SM; Juliano, RL; Grandas, A. Retro-1-Oligonucleotide Conjugates. Synthesis and Biological Evaluation (2019) Molecules 24(3).PMCID: PMC6384773.
- Jaramillo, AM; Piccotti, L; Velasco, WV; Delgado, ASH; Azzegagh, Z; Chung, F; Nazeer, U; Farooq, J; Brenner, J; Parker-Thornburg, J; Scott, BL; Evans, CM; Adachi, R; Burns, AR; Kreda, SM; Tuvim, MJ; Dickey, BF. Different Munc18 proteins mediate baseline and stimulated airway mucin secretion (2019) JCI Insight 4(6). PMCID: PMC6483006.
- Schultz, A; Puvvadi, R; Borisov, SM; Shaw, NC; Klimant, I; Berry, LJ; Montgomery, ST; Nguyen, T; Kreda, SM; Kicic, A; Noble, PB; Button, B; Stick, SM. Airway surface liquid pH is not acidic in children with cystic fibrosis (2017) Nat Commun 8(1):1409. PMCID: PMC5680186
- Wang, L; Ariyarathna, Y; Ming, X; Yang, B; James, LI; Kreda, SM; Porter, M; Janzen, W; Juliano, RL. A novel family of small molecules that enhance the intracellular delivery and pharmacological effectiveness of antisense and splice switching oligonucleotides (2017) ACS Chem Biol 12(8):1999-2007. PMCID: PMC5662188
- Blackmon, RL; Kreda, SM; Sears, PR; Chapman, BS; Hill, DB; Tracy, JB; Ostrowski, LE; Oldenburg, AL. Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT (2017) Nanoscale 9(15):4907-4917. PMCID: PMC5473168
- Jones, L; Moussa, L; Fulcher, L; Yunxiang, Z; Hudson, E; O’Neal, WK; Randell, SH; Lazarowski, ER; Boucher RC; Kreda, SM. VAMP8 is the vesicle SNARE in mucin secretion in airway goblet cells (2012) J Physiol 590:545-561. PMCID: PMC3379700
- Kreda, SM; Davis, CW; Rose, MC. CFTR, mucins, and mucus obstruction in cystic fibrosis (2012) Cold Spring Harb Perspect Med 2(9):a009589. doi: 10.1101/cshperspect.a009589. Review. PMID: 22951447; PMCID: PMC3426818
- Seminario-Vidal, L; Okada, SF; Sesma J; Kreda, SM; van Heusden, CA; Zhu, Y; Jones, LC; O’Neal, WK; Penuela, S; Laird, DW; Boucher, RC; Lazarowski, ER. Rho signaling regulates pannexin 1-mediated ATP release from airway epithelia (2011) J Biol Chem 286:26277-86. PMCID: PMC3143590
- Kreda, SM; Vidal-Seminario, L; van Heusden, CA; O’Neal, WK; Jones, L; Boucher, RC; Lazarowski, ER. Receptor-promoted exocytosis of airway epithelial mucin granules containing a spectrum of adenine nucleotides (2010) J Physiol 588:2255-67. PMCID: PMC2911224
- Seminario-Vidal, L; Kreda, SM; Jones, L; O’Neal, W; Boucher, RC; Lazarowski, ER. Thrombin promotes release of ATP from lung epithelial cells through coordinated activation of Rho- and Ca2+-dependent signaling pathways (2009) J Biol Chem 284:20638-48. PMCID: PMC2673323
- Sesma, JI; Esther, CR; Kreda, SM; Jones, L; O’Neal, W; Nishihara, S; Nicholas, RA; Lazarowski, ER. Endoplasmic reticulum/golgi nucleotide sugar transporters contribute to the cellular release of UDP-sugar signaling molecules (2009) J Biol Chem 284:12572-83. PMCID: PMC2673323
- Kreda, SM; Okada, SF; van Heusden, CA; O’neal, W; Gabriel, S; Abdullah, L; Davis, CW; Boucher, RC; Lazarowski, ER. Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells (2007) J Physiol 584:245-259. PMCID: PMC2277076
- Kreda, SM; Mall, M; Mengos, A; Rochelle, L; Yankaskas, J; Riordan, JR; Boucher, RC. Characterization of wild-type and ΔF508 cystic fibrosis transmembrane regulator in human respiratory epithelia (2005) Mol Biol Cell 16:2154-2167. PMCID: PMC1087225
- Kreda, SM; Pickles, RJ; Lazarowski, E; Boucher, RC. G-protein-coupled-receptors as targets for gene transfer vectors using natural small-molecule-ligands (2000) Nat Biotechnol 18:635-640
|Kreda et al, 2001||Kreda et al, 2004||Kreda et al, 2005|
|Okada et al, 2006||Kreda et al, 2007||Mall et al, 2008|
|Kreda et al, 2008|
Members of Dr. Kreda’s lab:
Silvia (front, kneeling) walking with her certified therapy dog, Whiskey, and CF Center colleagues during the annual Chapel Hill Great Strides walk to raise awareness and funds for Cystic Fibrosis research.