|Wanda O'Neal, PhD, Associate Professor of Medicine|
The gene SCNN1B, or beta ENaC, has been identified as an important gene for sodium ion transport and airway surface liquid hydration. We have demonstrated that over-expressing the Scnn1b gene in transgenic mice gives a lung phenotype with many of the characteristics of the human disease, cystic fibrosis. The lungs exhibit chronic mucus accumulation, decreased mucocilliary clearance, and increased inflammation, all hallmarks of human disease. The availability of many different mouse strains and mutations now allow us to dissect the mechanisms and processes that are involved in the development of the observed phenotype. By crossing the Scnn1b mice to a variety of genetic variants, we are hoping to identify the key regulators in the development of the disease pathology.
We are interested in studying the interactions of mucins (tethered mucins 1,4,16, and secreted 5AC) to try to understand the roles of these proteins in viral infections, bacterial infections, and in mucus plugging and mucocilliary clearance.
The use of short-interfering RNAs(siRNA), which specifically interfere with gene expression, has become a highly useful methodology for studying the function of genes. We have developed a standardized method to introduce si/shRNA into airway cells in culture. By knocking down individual genes we are able to evaluate their role as it relates to Cystic Fibrosis through functional studies (Ussing chamber).
As the director of the Molecular Biology Core, I am continuing to push the CF Center at UNC forward and to keep it as competitive as possible in the grant market by evaluating new techniques in molecular biology. We are presently gaining expertise in RNA-sequencing technology, which utilizes the next generation sequencing technology that is becoming more widely available.
In the UNC Health Care and School of Medicine Newsroom, the article entitled: "The Family Disease" was published in April, 2015, and describes Dr. O'Neal's path to research.
Doctor of Philosophy- 1993 Baylor College of Medicine - Department of Molecular and Human Genetics, Houston, Texas.
Master of Science- 1987 North Dakota State University.
Crop Science Department, Fargo, North Dakota.
Bachelors of Science- 1984 North Dakota State University.
Plant Pathology and Crop Science, Fargo, North Dakota.
Professional Experience and Training
2002-Present Research Associate Professor and Director of Molecular Biology Core Laboratory CF/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill.
1998-2002 Research Assistant Professor and Director of Molecular Biology Core Laboratory - CF/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill.
1997-1998 Assistant Professor - Department of Molecular and Human Genetics
Baylor College of Medicine, Houston, Texas.
1993-1997 Postdoctoral Fellow - Supervising Professor: Arthur L. Beaudet, M.D.
Department of Molecular and Human Genetics,Baylor College of Medicine, Houston, Texas. Development of Adenovirus Vectors for Gene Therapy with Emphasis on Treatment of Genetic Disorders of the Lung and Liver.
1988-1993 Graduate Student - Advisor: Arthur L. Beaudet, M.D.
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas. Thesis Title: "Generation and Characterization of a Murine Model for Cystic Fibrosis."
1984-1987 Masters Degree Student and Graduate Teaching Fellow.
Advisor: Calvin Messersmith, Ph.D., Department of Crop Science.
North Dakota State University, Fargo, North Dakota .
Fellowships and Grants
2009-2014 NIH/NIDDK "Molecular Therapy Core Center, Core C: Molecular Core," Core Director.
2007-2012 NIH/NHLBI "Pumonary Epithelia in Health and Disease, Core B: Molecular and Protein Core," Core Director.
2007-2011 Cystic Fibrosis Foundation "Epithelial Function in Cystic Fibrosis, Core E. Molecular Biology and Mouse Core" Core Director.
2009-2016 NIH/NHLBI "SPIROMICS Genomics and Informatics Center" Co-investigator.
2008-2012 NIH/NHLBI "Molecular Phenotypes for Cystic Fibrosis Lung Disease," Co-investigator.
2009-2010 NIH/NCRR "Development of the betaENaC Model of Cystic Fibrosis for Translational Research," Sub-contract Principal Investigator.
2001-2004 Cystic Fibrosis Foundation Research Grant "CF Therapeutic Targets Revealed by Expression Arrays," Principal Investigator.
2007-2009 Cystic Fibrosis Foundation "Epithelial Function in Cystic Fibrosis, Project 2. Transmembrane Mucin Function in Mucociliary Clearance," Principal Investigator.
2007-2009 Cystic Fibrosis Foundation, "Dysregulated Airway Physiology in Scnn1b Transgenic Mice." Co-investigator.
2007-2009 Cystic Fibrosis Foundation, "CF Modifiers Defined by Scnn1b Over-expressing mice," Principal Investigator.
2006-2008 NIH/NIDDK "Molecular Therapy Core Center, Project 6: Interfering RNA for Modulation of ENaC Function," Project Leader.
2001-2006 NIH/NHLBI "Pulmonary Epithelia in Health and Disease", Core B, Molecular Core, Principal Investigator.
2001-2006 "Gene Therapy for Pulmonary and Hematologic Disorders, Project 3: Extra Cellular Barriers to Gene Transfer in the Lung", Co-Investigator (10% effort).
2002-2006 NIH/NHLBI "A Ciliated Cell-specific Promoter for Gene Therapy of CF", Co-Investigator (10% effort)
2002-2006 Cystic Fibrosis Foundation "Molecular Core", Principal Investigator.
2001-2005 NIH/NHLBI & NIDDK "Enhanced Gene Transfer to Lung Epithelia", Co-investigator (10% effort)
2000-2002 Cystic Fibrosis Foundation, Gene Therapy Pilot and Feasibility Grant "MUC-4 as aBarrier to Lung Gene Transfer," Principal Investigator.
2000-2001 Cystic Fibrosis Foundation Research Grant "In Vitro Cell Models for CFTR Expression," Principal Investigator.
1998-2000 NIDDK R21 Grant: "Large Deletion Adenoviral Vectors for Cystic Fibrosis," Principal Investigator.
1994-1997 Cystic Fibrosis Foundation Postdoctoral Fellowship.
1993-1994 Postdoctoral Fellowship - NIH Training Grant.
1989-1993 March of Dimes Graduate Student Fellowship.
1985-1988 Graduate Teaching Fellowship, North Dakota State University.
Please see Pubmed feed in the righthand column for links to current publications.
Randell, S.H., O'Neal, W.K., Martsen, E.O., Noone, P.G., Zhou, Z., Plonk, M.K., Wu, Q., Knowles, M.R., Boucher,
R.C., and Gabriel, S.E. 2001. mRNA expression profiling of human airway epithelium. North American
Cystic Fibrosis Conference.
Holda, J.R., Pickles, R.J., Burns, K.A., Gendler, S.J., Boucher, R.C., and O'Neal, W.K. 2001. Muc1 is a significant
component of mouse airway lumenal glycocalyx. North American Cystic Fibrosis Conference.
Mall, M., Boucher, R.C., and O'Neal, W.K. 2001. The novel ubiquitin-protein ligase Nedd 4.2 is co-expressed with
the amiloride-sensitive Na+ channel ENaC in human normal and CF airway epithelial cells. North American
Cystic Fibrosis Conference.
Zhang, Y.J., O'Neal, W.K., Blackburn, K., Moyer, M., Moseley, R., Boucher, R., and Ostrowski, L. 2001.
Identification and characterization of an axonemal dynein heavy chain reduced in cilia from a patient with
primary ciliary dyskinesia. American Thoracic Society.
Lazarowski, E., Grubb, B.R., O'Neal, W.K., Ribeiro, C.P., Burch, N. and Boucher, R.C. 2000. Regulation of
gastrointestinal ion secretory responses by uridine nucleotide receptors. North American Cystic Fibrosis
Morse, K.M., O'Neal, W.K., Patel, M., Davis, C.W., and Olsen, J.C. 2000. An ecdysone-inducible expression
system for use with retroviral vectors. Mol. Ther. 1: S186-187.
O'Neal, W.K., Wang, Y., Taylor, K., and Beaudet, A.L. 1997. Advantages of a-fetoprotein (AFP) as a reporter
The Cystic Fibrosis Foundation.
|Group with Dr. Wanda O'Neal, Research Assistant Professor
||Lisa Jones, Research Specialist||Rodney C. Gilmore, Research Specialist|
|Brian Brighton, Research Specialist||Kristy Terrell, Research Specialist||Caitlin Neal, Undergraduate Research Assistant
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599
Phone: (919) 962-9866
Fax: (919) 966-6821