Jaclyn Stonebraker, PhD

Research Publications Contact

Jaclyn Stonebraker, Ph.D., is a Research Associate Scientist working with Dr. Michael R Knowles.

Research Focus

Only a subset of cystic fibrosis (CF) patients develop severe liver disease (biliary cirrhosis with portal hypertension; CFLD), and thisdoes not correlate with the type of CF gene (CFTR) mutation. Thus, there must be other (non-CFTR) genetic variation that contributes to the development of CFLD. The goals of our research are to study candidate genes that might modify CF liver disease, analyze genome-wide association study (GWAS) of 570,000 genetic markers (SNPs) in patients with CFLD, enroll additional patients with CFLD, and perform another GWAS in additional patients with CFLD. The long term goal of our research is to identify the major gene modifiers for CFLD, which will provide the opportunity for a novel, genetic-based technique to identify CF children at risk for CFLD. If successful, our study will provide novel prognostic approaches, and identification of novel, targeted therapies to prevent severe biliary cirrhosis before it occurs in CF children.

Publications

1: Sun L, Rommens JM, Corvol H, Li W, Li X, Chiang T, Lin F, Dorfman R, Busson P-F, Parekh RV, Zelenika D, Blackman S, Corey M, Doshi V, Henderson L, Naughton K, O'Neal WK, Pace RG, Stonebraker JR, Wood SD, Wright FA, Zielenski J, Clement A, Drumm ML, Boëlle P-Y, Cutting GR, Knowles MR, Durie PR, Strug LJ. The hypothesis-driven GWAS identifies ‘missing heritability’ in modifiers of disease phenotypes: Application to meconium ileus in cystic fibrosis. Nat Genet. 2012;44(5):562-9.PMID: 22466613.

2: Guo X, Pace RG, Stonebraker JR, Commander CW, Dang AT, Drumm ML, Harris A, Zou F, Swallow DM, Wright FA, O'Neal WK, Knowles MR. Mucin variable number tandem repeat polymorphisms and severity of cystic fibrosis lung disease: significant association with MUC5AC. PLoS One. 2011;6(10):e25452. Epub 2011 Oct 6.PMID:2199866.

3: Wright FA, Strug LJ, Doshi VK, Commander CW, Blackman SM, Sun L, Berthiaume Y, Cutler D, Cojocaru A, Collaco JM, Corey M, Dorfman R, Goddard K, Green D, Kent JW Jr, Lange EM, Lee S, Li W, Luo J, Mayhew GM, Naughton KM, Pace RG, Paré P, Rommens JM, Sandford A, Stonebraker JR, Sun W, Taylor C, Vanscoy LL, Zou F, Blangero J, Zielenski J, O'Neal WK, Drumm ML, Durie PR, Knowles MR, Cutting GR. Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. Nat Genet. 2011 Jun;43(6):539-46. Epub 2011 May 22. PubMed PMID: 21602797.

4: Taylor C, Commander CW, Collaco JM, Strug LJ, Li W, Wright FA, Webel AD, Pace RG, Stonebraker JR, Naughton K, Dorfman R, Sandford A, Blackman SM, Berthiaume Y,Paré P, Drumm ML, Zielenski J, Durie P, Cutting GR, Knowles MR, Corey M. A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis Genetic modifier studies. Pediatr Pulmonol. 2011. Sep;46(9):857-69. doi: 10.1002/ppul.21456. Epub 2011 Apr 1. PMID: 21462361.

5: Bartlett (Stonebraker) JR, Friedman KJ, Ling SC, Pace RG, Bell SC, Bourke B, Castaldo G, Castellani C, Cipolli M, Colombo C, Colombo JL, Debray D, Fernandez A, Lacaille F, Macek M Jr, Rowland M, Salvatore F, Taylor CJ, Wainwright C, Wilschanski M, Zemková D, Hannah WB, Phillips MJ, Corey M, Zielenski J, Dorfman R, Wang Y, Zou F, Silverman LM, Drumm ML, Wright FA, Lange EM, Durie PR, Knowles MR; Gene Modifier Study Group. Genetic modifiers of liver disease in cystic fibrosis. JAMA. 2009 Sep 9;302(10):1076-83. PubMed PMID: 19738092.

6: Hirsh AJ, Stonebraker JR, van Heusden CA, Lazarowski ER, Boucher RC, Picher M. Adenosine deaminase 1 and concentrative nucleoside transporters 2&3 regulate adenosine on the apical surface of human airway epithelia: implications for inflammatory lung diseases. Biochemistry. 2007 Sep 11;46(36):10373-83. Epub 2007 Aug 15. PubMed PMID: 17696452.

7: Morin-Kensicki EM, Boone BN, Howell M, Stonebraker JR, Teed J, Alb JG, Magnuson TR, O'Neal W, Milgram SL. Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Mol Cell Biol. 2006 Jan;26(1):77-87. PubMed PMID: 16354681; PubMed Central PMCID: PMC1317614.

8: Neuringer IP, Sloan J, Budd S, Chalermskulrat W, Park RC, Stonebraker JR, O'Neal WK, Aris RM, Randell SH. Calcineurin inhibitor effects on growth and phenotype of human airway epithelial cells in vitro. Am J Transplant. 2005 Nov;5(11):2660-70. PubMed PMID: 16212625.

9: Stonebraker JR, Wagner D, Lefensty RW, Burns K, Gendler SJ, Bergelson JM, Boucher RC, O'Neal WK, Pickles RJ. Glycocalyx restricts adenoviral vector access to apical receptors expressed on respiratory epithelium in vitro and in vivo: role for tethered mucins as barriers to lumenal infection. J Virol. 2004 Dec;78(24):13755-68. PubMed PMID: 15564484; PubMed Central PMCID: PMC533903.

10: Holda (Stonebraker) JR, Klishin A, Sedova M, Hüser J, Blatter LA. Capacitative Calcium Entry. News Physiol Sci. 1998 Aug;13:157-163. PubMed PMID: 11390782.

11: Hüser J, Holda (Stonebraker) JR, Kockskamper J, Blatter LA. Focal agonist stimulation results in spatially restricted Ca2+ release and capacitative Ca2+ entry in bovine vascular endothelial cells. J Physiol. 1999 Jan 1;514 ( Pt 1):101-9. PubMed PMID: 9831719; PubMed Central PMCID: PMC2269050.

12: Holda (Stonebraker) JR, Blatter LA. Capacitative calcium entry is inhibited in vascular endothelial cells by disruption of cytoskeletal microfilaments. FEBS Lett. 1997 Feb 17;403(2):191-6. PubMed PMID: 9042964.

13: Byron KL, Puglisi JL, Holda (Stonebraker) JR, Eble D, Samarel AM. Myosin heavy chain turnover in cultured neonatal rat heart cells: effects of [Ca2+]i and contractile activity. Am J Physiol. 1996 Nov;271(5 Pt 1):C01447-56. PubMed PMID: 8944626.

14: Holda (Stonebraker) JR, Oberti C, Perez-Reyes E, Blatter LA. Characterization of an oxytocin-induced rise in [Ca2+]i in single human myometrium smooth muscle cells. Cell Calcium. 1996 Jul;20(1):43-51. PubMed PMID: 8864570.

15: Gasser KW, Holda (Stonebraker) JR. The effect of phospholipase A2 on chloride transport by pancreatic secretory granules. Biochim Biophys Acta. 1994 Aug 24;1194(1):123-30. PubMed PMID: 8075126.

16: Gasser KW, Holda (Stonebraker) JR. ATP-sensitive potassium transport by pancreatic secretory granule membrane. Am J Physiol. 1993 Jan;264(1 Pt 1):G137-42. PubMedPMID: 8430796.

Contact Information

5011 Thurston-Bowles Bldg.
The Univeristy of North Carolina at Chapel Hill
Campus Box #7248
Chapel Hill, NC 27599
Phone: (919) 966-0713
Fax: (919) 843-7659

Email: Jaclyn_Stonebraker@med.unc.edu

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