Silvia M Kreda

Specialty Areas:

Oligonucleotide-based therapeutic strategies for lung diseases. Delivery of therapeutic oligonucleotides to the lung and other non-hepatic organs. Targeting of therapeutic molecules to the airway epithelium. Regulation of mucin secretion in lung diseases.

Research:

Dr. Kreda’s laboratory studies mechanisms of delivery of therapeutic molecules in the lung. The main goal is to develop novel and efficient delivery strategies of therapeutic nucleic acids in obstructive lung diseases. The Kreda laboratory is currently involved in designing an efficacious oligonucleotide-based therapeutic approach to correct cystic fibrosis mutations in patients resilient to modulator therapies (press release June 2021) and orphan mutations that cause primary ciliary dyskinesia (PCD). The PCD studies have recently received funding from the Eshelman Institute for Innovation (see the following links: Silvia M. Kreda to Study Novel Therapeutic Strategy for Primary Ciliary Dyskinesia and Funded Projects – The Eshelman Institute for Innovation [in the 2022 tab]) and NC TraCS (see the following links: NC TraCS Award Announcements and Kreda, Leigh, & Ostrowski Selected for SOM Translational Team Science Award). The laboratory uses state-of-the art technologies and patient-oriented models for precision and personalized medicine approaches.

Dr. Kreda’s research focuses also on identifying signaling molecules/pathways that regulate airway mucin secretion. The main goal is to uncover potential targets of clinical interest to control abnormal luminal mucus accumulation in lung diseases. Her laboratory has developed and optimized in vitro and in vivo models of lung diseases with excessive mucus production and quantitative assays for therapeutic drug testing and evaluation of mucin production in airway epithelia.

Dr. Kreda’s laboratory and scientific studies are fully funded by competitive grants from different sources including the National Institutes of Health (NIH), Cystic Fibrosis Foundation, NCTraCS (the NIH CTSA at UNC-CH), Eshelman Institute for Innovation, Initos Pharmaceuticals, 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.

Chronology:

• Silvia M. Kreda is a faculty member of the Marsico Lung Institute/Cystic Fibrosis Center; an Associate Professor in the Department of Medicine and the Department of Biochemistry and Biophysics.
• 1994 IRTA fellow at NIEHS, RTP NC
• 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

Selected Publications:

link to all pubs My Bibliography

1. Kreda S. Oligonucleotide-based therapies for Cystic Fibrosis. Curr Opin Pharmacol. 2022 Oct;66:102271. doi: 10.1016/j.coph.2022.102271. PMID: 35988291.
2. Dang Y, van Heusden C, Nickerson V, Chung F, Wang Y, Quinney NL, Gentzsch M, Randell SH, Moulton HM, Kole R, Ni A, Juliano RL, Kreda SM. Enhanced delivery of peptide-morpholino oligonucleotides with a small molecule to correct splicing defects in the lung. Nucleic Acids Res. 2021 Jun 21;49(11):6100-6113. doi: 10.1093/nar/gkab488. PMID: 34107015; PMCID: PMC8216463.
3. 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. JCI Insight.2019 Mar 21;4(6):e124815. PMID: 30721150; PMCID: PMC6483006.
4. 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. ACS Chem Biol. 2017 Aug 18;12(8):1999-2007. PMID: 28703575; PMCID: PMC5662188
5. 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. Nanoscale. 2017 Apr 13;9(15):4907-4917. PMID: 28358158; PMCID: PMC5473168
6. 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. J Physiol. 2012 Feb 1;590(3):545-62. PMID: 22144578; PMCID: PMC3379700
7. Kreda, SM; Davis, CW; Rose, MC. CFTR, mucins, and mucus obstruction in cystic fibrosis. Cold Spring Harb Perspect Med. 2012 Sep 1;2(9):a009589. doi: 10.1101/cshperspect.a009589. Review. PMID: 22951447; PMCID: PMC3426818
8. 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. J Physiol. 2010 Jun 15;588(Pt 12):2255-67. PMID: 20421285; PMCID: PMC2911224
9. 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. J Physiol. 2007 Oct 1;584(Pt 1):245-59. PMID: 17656429; PMCID: PMC2277076
10. 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. Mol Biol Cell. 2005 May;16(5):2154-67. PMID: 15716351; PMCID: PMC1087225
11. Kreda, SM; Pickles, RJ; Lazarowski, E; Boucher, RC. G-protein-coupled-receptors as targets for gene transfer vectors using natural small-molecule-ligands. Nat Biotechnol. 2000 Jun;18(6):635-40. PMID: 10835601.