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Nedra Faye Wilson , Ph.D.
Associate Professor of Anatomy

nedra.wilson@okstate.edu
918-561-8256

Education | Professional Experience |Awards & Fellowhsips | Memberships | Other Activities | Presentations | Publications | Research Interests

Education

1990-1996
Ph.D. (Cell Regulation Graduate Program)
University of Texas Southwestern Medical Center at Dallas
Dallas, TX
Thesis advisor: Dr. William J. Snell

1981-1985
B.S. (Biology with Cell Emphasis)
Northeastern State University
Tahlequah, OK

1980
Bacone College
Muskogee, OK

Professional Experience

1998-2005
Post-doctoral Fellow
Department of Plant Biology
University of Minnesota
St. Paul, MN
Supervisor:  Dr. Paul A. Lefebvre

1996-1998
Post-doctoral Fellow
Department of Cell Biology and Neuroscience
University of Texas Southwestern Medical Center at Dallas
Dallas, TX
Supervisor:  Dr. William J. Snell

1990-1996
Doctoral Student
Cell Regulation Graduate Program                   
University of Texas Southwestern Medical Center at Dallas
Dallas, TX
Supervisor:  Dr. William J. Snell

1988-1990
Research Technician
Department of Internal Medicine – Liver Unit
University of Texas Southwestern Medical Center at Dallas
Dallas, TX
Supervisor:  Dr. Dwain Theile

1981-1984
Student Research Technician
Minority Biomedical Research Support Program
Department of Math and Biology
Northeastern State University
Tahlequah, OK
Supervisor:  Dr. Gary VanDenbos

Formal Teaching Experience

2002
Guest Lecturer – Cell Biology (Map kinase signal transduction)
University of Minnesota

1994-1996
Cell-Cell Interaction (plant/mammalian fertilization; viral-cell and cell-cell fusion)
Cell Regulation Graduate Program
University of Texas Southwestern Medical Center at Dallas
Dallas, TX

Informal Teaching Experience

2002-2003
Supervised undergraduate students (2) in honors research
University of Minnesota

1998-present
Chlamydomonas Research Discussion Group
University of Minnesota College of Biological Sciences
University of Minnesota School of Medicine

1992-1998
Supervised laboratory technicians (Univ of TX Southwestern Medical Center): 
4 technicians

1990-1998
Supervised summer research fellows (Univ of TX Southwestern Medical Center):  
1 high school student (MARC program)
1 junior high school science teacher (MARC program)
1 high school science teacher, Science Teacher Access to Resources at Southwestern
2 undergraduate students

1994-1997
Co-organized Cell Biology Departmental Works–In–Progress weekly seminars
Department of Cell Biology and Neuroscience
University of Texas Southwestern Medical Center at Dallas
Dallas, TX

1988-1990
Trained rotating graduate students
Department of Internal Medicine – Liver Unit
University of Texas Southwestern Medical Center at Dallas
Dallas, TX

Awards & Fellowships

• NIH Post-doctoral fellowship, University of Minnesota, St. Paul, MN, 1999-2001
• American Cancer Society Post-doctoral fellowship – declined, University of Minnesota, St. Paul, MN, 1999
• NSF Cytoskeleton Training Grant, 1998-1999
• NIH Supplemental for Pre-doctoral training, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 1993-1996
• American Society for Cell biology/Pfizer Award for best Graduate Student Poster, Minorities Poster Session, 34^th Annual American Society for Cell Biology, 1996
• Individual National Research Service Award, Minority Access to Research Careers Pre-doctoral fellowship – declined, University of Texas Southwestern Medical Center at Dallas, 1993

Memberships

• American Society for Cell Biology
• Genetics Society of America

Other Activities

• Ad hoc reviewer:  Eukaryotic Cell
• Assisted with genome annotation of Chlamydomonas reinhardtii; DOE Joint Genome Institute; Walnut Creek, CA., 2003

Presentations

Characterization of LF4, a regulator of flagellar length in Chlamydomonas.
11th International Conference on the Cell and Molecular Biology of Chlamydomonas; Kobe, Japan, 2004

Characterization of GSK3, a flagellar kinase with a putative role in the regulation of flagellar length. 10th International Conference on the Cell and Molecular Biology of Chlamydomonas; Vancouver, BC; Canada, 2002

Regulation of flagellar length in Chlamydomonas. Primary and Sensory Cilia Special Interest Subgroup; 41st Annual Meeting of the American Society for Cell Biology; Washington, DC, 2001

Pharmacology of flagellar length control. 9th International Conference on the Cell and Molecular Biology of Chlamydomonas; Nordweijkerhout, The Netherlands, 2000

Adhesion-induced phosphorylation of a homeodomain protein in mt+ gametes during fertilization. 8th International Conference on the Cell and Molecular Biology of Chlamydomonas; Tahoe City, CA, 1998

Isolation and characterization of fertilization tubules from Chlamydomonas mt+  gametes. 7th International Conference on the Cell and Molecular Biology of Chlamydomonas; Regensburg, Germany, 1996

Publications

Wilson, N.F., and P.A. Lefebvre. 2004. Regulation of flagellar assembly by glycogen synthase kinase 3 in Chlamydomonas reinhardtii. Eukaryot. Cell. 3:1307-1319.

Berman, S.A., Wilson, N.F., Haas, N.A., and P.A. Lefebvre. 2003. A novel MAP kinase regulates flagellar length in Chlamydomonas. Curr. Biol. 13:1145-1149.

Wilson, N.F., O’Connell, J.S., and W.J. Snell. 1999. Flagellar adhesion between mt (+) and mt(-) Chlamydomonas gametes regulates phosphorylation of the mt(+)-specific homeodomain protein GSP1. J. Biol. Chem. 274:34383-34388.

Wilson, N.F., and W.J. Snell. 1998. Microvilli and cell-cell fusion during fertilization. Trends in Cell Biol. 8:93-96.

Wilson, N.F., Foglesong, M.J., and W.J. Snell. 1996. Isolation and characterization of a cell fusion organelle: the fertilization tubule of mt+ gametes of Chlamydomonas. J. Cell Biol. 137:1537-1553.

Wilson, N.F. 1996. The Chlamydomonas mt+ fertilization tubule: a model system for studying the role of cell fusion organelles in gametic cell fusion. Dissertation.

Manuscripts Submitted:

Wilson, N.F., and P.A. Lefebvre. 2006. LF4, a MAP kinase that regulates flagellar length, is a cargo for intraflagellar transport in Chlamydomonas. submitted to Mol. Biol. Cell

Manuscripts in Prep:

Wilson, N.F. 2006. A genomic perspective of MAP kinases in Chlamydomonas reinhardtii

Wilson, N.F. 2006. Genome-wide annotation of dual specificity phosphatases in Chlamydomonas reinhardtii

Abstracts:

Wilson, N.F., and P.A. Lefebvre. 2005. LF4, a regulator of flagellar length in Chlamydomonas, is a cargo for transport by IFT. 45th Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Wilson, N.F., Berman, S.A., and P.A. Lefebvre. 2003. Characterization of LF4p, a MAP kinase involved in the regulation of flagellar length. 5th Cold Spring Harbor meeting on Protein phosphorylation and cell signaling; Cold Spring Harbor Laboratory; Cold Spring Harbor, NY

Wilson, N.F., and P.A. Lefebvre. 2003. A MAP kinase pathway regulates flagellar length in Chlamydomonas. 43rd Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Wilson, N.F., Berman, S.A., and P.A. Lefebvre. 2002. Characterization of LF4p, a flagellar protein involved in the regulation of flagellar length. 42nd Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Wilson, N.F. and P.A. Lefebvre. 2001. Characterization of GSK-3, a putative regulator of flagellar length in Chlamydomonas. 41st Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Wilson, N.F., and P.A. Lefebvre. 2000. Characterization of GSK-3, a potential regulator of flagellar length in Chlamydomonas. 40th Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Wilson, N.F. and P.A. Lefebvre. 1999. Pharmacological analysis of the regulation of flagellar length in Chlamydomonas. 39th Annual Meeting of the American Society for Cell Biology; Washington, D.C.

Wilson, N.F., O’Connell, J.S., and W.J. Snell. 1997. Adhesion-induced modification of an mt+ gamete-specific homeodomain protein during fertilization in Chlamydomonas. 37th Annual Meeting of the American Society for Cell Biology; Washington, D.C.

Wilson, N.F., and W.J. Snell. 1997. Studies on adhesion/fusion of mt+ fertilization tubules and the mt+ mating structure in Chlamydomonas gametes. 37th Annual Meeting of the American Society for Cell Biology; Washington, D.C.

Wilson, N.F., O’Connell, J.S., and W.J. Snell. 1997. Adhesion-induced modification of an mt+ gamete-specific homeodomain protein during fertilization in Chlamydomonas.  Gordon Research Conference on Fertilization and Activation of Development; Holderness, N.H.

Wilson, N.F., Foglesong, M.J., and W.J. Snell. 1997. Isolation and characterization of a cell fusion organelle: the fertilization tubule of Chlamydomonas gametes. Gordon Research conference on Fertilization and Activation of Development; Holderness, N.H.

Wilson, N.F., Foglesong, M.J., and W.J.Snell. 1996. Isolation and characterization of a cell fusion organelle: the fertilization tubule of Chlamydomonas mt+ gametes. 36th Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Wilson, N.F., Huang, G., and W.J. Snell.  1994.  Analysis of the fertilization tubule in Chlamydomonas by cell fractionation and insertional mutagenesis. 6th International Conference on the Cell and Molecular Biology of Chlamydomonas; Tahoe City, CA.

Wilson, N.F., Huang, G., Fletcher, G., and W.J. Snell. 1994. Analysis of cell fusion in Chlamydomonas. 34th  Annual Meeting of the American Society for Cell Biology; San Francisco, CA.

Snell, W.J., Zhang, Y., and N.F. Wilson. 1992. Differential regulation of vegetative and gametic forms of adenylyl cyclase in flagella of Chlamydomonas. 5th International Conference on the Cell and Molecular Biology of Chlamydomonas; Pacific Grove, CA.

Kincade, R., Wilson, N.F., VanDenbos, G., and L. Reed. 1983. Computer assisted instruction for the estimation of certain macromolecular components of biological tissue. 11th Annual MBRS Symposium; Washington, D.C.

Wilson, N.F., Lawrence, J., Conrad, T.G., and G. VanDenbos. 1983. The development of an animal model to quantitate the effect of thyroid hormone on ribonucleotide reductase activity. 11th Annual MBRS Symposium; Washington, D.C.

Research Interests

Regulation of Flagellar Assembly
The major focus of my lab is to understand the cellular and molecular mechanisms that regulate the assembly of cilia and flagella. Cilia and flagella are found on most mammalian cells and function to provide motility to cells (i.e., sperm cells) and in the movement of fluids (mucus or water) over the surface of cells. In addition, non-motile cilia function as sensory organelles. For example, the non-motile cilia of kidney epithelial cells act as mechanosensors for fluid flow through kidney tubules. Defects in the assembly of cilia or flagella result in a number of human diseases including infertility, retinitis pigmentosa, hydrocephaly, polycystic kidney disease, primary ciliary dyskinesia, and situs inversus.  In addition, assembly of cilia to inappropriate lengths also has deleterious effects on human health. Recurrent respiratory infections were observed in patients diagnosed with primary ciliary dyskinesia. These patients assembled cilia up to twice the length of normal respiratory cilia. These abnormally long cilia are unable to beat effectively and thus clear inhaled particles from the lungs. While cilia and flagella are widely studied, we know little about the cellular and molecular mechanisms that underlie the regulation of ciliary and flagellar length.

We use the unicellular eukaryote Chlamydomonas as a model system for our studies. Chlamydomonas is a biflagellate alga that is amenable to biochemical, genetic, and molecular genetic approaches. Because flagella are not essential for life in Chlamydomonas, it is relatively easy to generate and isolate mutants that are defective in different aspects of flagellar assembly or function. In fact most of our knowledge about ciliary assembly and function has come from studies of Chlamydomonas mutants. Many of the genes found to be defective in the human diseases listed above were first identified in Chlamydomonas. We will use a collection of flagellar mutants known as long flagella (lf) mutants to elucidate the signal transduction pathway that regulates flagellar length. Genetic studies have identified 4 genes (LF1, LF2, LF3, and LF4) that when mutated generate cells with abnormally long flagella. LF4 was recently shown to encode a MAP kinase homologous to the mammalian MAP kinase MOK. My current research is focused on elucidating the role of LF4 in the regulation of flagellar length.

PMA-induced flagellar disassembly
The addition of mM concentrations of the phorbol ester PMA to flagellated cultures results in the rapid disassembly (within 5 minutes) and reassembly of flagella. Currently, we are interested in developing methods to monitor the effects on flagella as well as begin to identify targets that are modified by PMA. This project includes:  cell biological analysis of PMA effects on flagellar lengths; and biochemical identification of targets for PMA. Once identified, immunological probes for PMA targets will be generated and used for their further characterization.

Identification of SHF genes
The recent sequencing of the Chlamydomonas genome combined with the generation of physical and molecular maps should allow the identification of candidate SHF genes. Once identified, candidate genes will be sequenced in shf strains to identify mutations. Candidate SHF genes will be confirmed by transformation of the shf strain with the wild-type SHF gene and effect on flagellar length will be determined. This project includes molecular biology to clone candidate SHF genes; biochemical and immunological analysis of candidate SHF genes.

Current Projects:

Characterizing LF4p MAP kinase. LF4p is present as different isoforms in cell bodies and flagella. In cell bodies, LF4p migrates as a doublet of 72/73 kDa while in flagella LF4p migrates as a single band of 65 kDa. Using immunoblot analysis and in-gel kinase assays, we demonstrated that in cell bodies, LF4p is phosphorylated on the TEY motif and thus is an active kinase. In contrast, in flagella the TEY motif of LF4p is unphosphorylated and thus is maintained in an inactive state. Using biochemical approaches, we have substantial evidence that a phosphatase maintains LF4p in an inactive state in flagella. Current projects include identifying the kinase and phosphatase that regulate the phosphorylation state of the TEY motif in both cell bodies and flagella. Both biochemical purification and molecular genetic approaches including RNAi technology will be used.

Identifying targets for regulation by LF4p.  The observation that null mutants of LF4 have long flagella suggests that the function of LF4 is to shorten flagella. To identify potential targets for regulation by LF4p, we will examine the phosphorylation levels of proteins in cells with full-length flagella, growing flagella and shortening flagella. This project would initially include: biochemical identification and characterization of LF4p targets; subcellular localization of targets; molecular and genetic characterization of targets by generation of point mutants and RNAi technology.