OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FIVE PAGES.
NAME: Jean M. Wilson
eRA COMMONS USER NAME (credential, e.g., agency login): JMWILSON
POSITION TITLE: Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training
and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
Completion
Date
MM/YYYY
University of California, Riverside
B.S.
04/1980
Biology
University of California, Davis
Ph.D.
06/1985
Anatomy
Harvard Medical School
Postdoctoral
06/1989
Cell Biology
Instit. de Biochemie, Univ. Lausanne, Switzerland
Postdoctoral
06/1988
Molecular Biology
FIELD OF STUDY
A. Personal Statement
The research in my laboratory focuses on membrane trafficking in polarized cells, with an emphasis on how
functional membrane domains are generated and maintained. As a graduate student I performed
transmission electron microscopic studies of transepithelial transport across the yolk sac. These studies led
naturally to post-doctoral studies of endosomal structure in the intestine. This interest has continued, and I
have investigated various aspects of endocytosis, recycling, and degradation of membrane proteins in
epithelial cells and neurons. Using morphological, biochemical, and molecular biological approaches, I led
studies into the mechanisms of biogenesis and targeting of endosomal proteins, polarized targeting of apical
proteins, and trafficking of tight junction proteins. The role of membrane trafficking in the establishment and
maintenance of epithelial polarity is an area that I find particularly fascinating. Loss of polarity is a hallmark of
cancer, and current paradigms suggest that loss of polarity may be an early event in the transformation
process. My laboratory has extensive experience with the culture, manipulation, transfection, and imaging of
mammalian cells. We use these approaches to define how membrane trafficking regulates morphogenesis,
signaling, and fate in normal cells and how changes in these pathways could lead to cancer. My membership
in the University of Arizona Cancer Center has opened opportunities for collaboration in my cancer-related
research.
B. Positions and Honors
Positions and Employment
1990-1997
Assistant Professor, Cell Biology and Anatomy, College of Medicine, University of
Arizona, Tucson, AZ.
1997-2003
Associate Professor, Cell Biology and Anatomy, College of Medicine, University of
Arizona, Tucson, AZ.
2003-present
Professor, Cellular and Molecular Medicine, College of Medicine, University of Arizona,
Tucson, AZ
Other Experience and Professional Memberships
1985-present
Member, American Society for Cell Biology
2001-present
Member, Cancer Biology Graduate Interdisciplinary Program
2002-present
Member, Committee on Neuroscience
2005-2008
Member, MBPP NIH study section
2006-present
Member, Arizona Cancer Center
2009-present
Member, Bio5 Research Institute
2012-present
Member, GMPB NIH study section
Honors
1999
2000
2014
University of Queensland Visiting Scholar Travel Award
Furrow Award for Excellence in Graduate Education Teaching
Outstanding Achievement in Teaching by a Block, Year II (Contributing faculty)
C. Contributions to Science
1. Membrane Trafficking in the Intestine
Our understanding of membrane trafficking pathways in epithelia was in its infancy when I began my
postdoctoral studies. In particular, whether or not endosomes existed as stable structures in the cell or were
merely transient intermediates was a matter of controversy. To address this, we isolated the apical
endosomal compartment from developing rat intestine and generated monoclonal antibodies against these
membranes. We identified Endotubin (EDTB) as an integral membrane protein that was resident in early
endosomes. In later work, we showed that EDTB is targeted to a distinct endosomal compartment in both
polarized and non-polarized cells, demonstrating that this specialized endosomal compartment exists in all
cell types. This was one of the first demonstrations of endosomes as a stable organelle. In addition, we have
now shown that endotubin has important roles in the regulation of tight junction integrity (described below). I
was the primary researcher in the early studies of endotubin, and served as the Principal Investigator for the
later studies.
a. Wilson, J.M. , J.A. Whitney, and M.R. Neutra. 1987. Identification of an endosomal antigen specific
to absorptive cells of suckling rat ileum. J. Cell Biol. 105:691-703.
b. Speelman B.A., K.A. Allen, M.R. Neutra, T. Kirchhausen, and J.M Wilson. 1995. Molecular
characterization of an early endosomal glycoprotein found in developing rat intestine. J. Biol. Chem.
270:1583-1588.
c. Wilson, J.M. and T.L. Colton. 1997. Targeting of an intestinal apical endosomal protein to
endosomes in non-polarized cells. J. Cell Biol. 136:319-330.
d. Gokay, K.E. and J.M. Wilson. 2000. Targeting of an intestinal apical endosomal protein to apical
endosomes in MDCK cells requires two sorting motifs. Traffic. 1:354-365.
2. Tight Junction Assembly, Regulation, and Control of Proliferation
Tight junctions have historically been viewed as static, stable structures that control the paracellular
movement of macromolecules and ions. However, recent work has shown that tight junctions undergo
continuous remodeling and recycling. Our studies of the endosomal protein EDTB and Rab14 have led us to
the discovery of the importance of endosomal regulation on tight junction assembly and signal transduction.
We have shown that EDTB is required for normal junction assembly and that Rab14 is an essential regulator
of junctional integrity through interaction with PKC. In addition, we discovered a surprising role for endotubin
in contact-mediated inhibition of proliferation through interaction of endotubin with the tight junction protein
angiomotin and downstream regulation of the oncoprotein YAP. These results have important implications for
the role of membrane trafficking in the control of proliferation. I was the Principal Investigator for all of these
studies.
a. McCarter, S., D. Johnson, K.N. Kitt, C. Donohue, A.E. Adams and J.M. Wilson. 2010. Regulation of
tight junction assembly and epithelial polarity by a resident protein of apical endosomes. Traffic
11:856-866
b. Lu, R., D.L. Johnson, L. Stewart, K. Waite, and J.M. Wilson. 2014. Rab14 regulates epithelial lumen
morphogenesis through regulation of claudin-2 trafficking. Molec Biol Cell 25:1744-54 PMCID:
PMC4038501
c. Lu,R, D. Dalgalan, E.K. Mandell, S.S. Parker, S. Ghosh and J.M. Wilson. 2015. PKC interacts with
Rab14 and regulates epithelial barrier function through regulation of claudin-2 levels. Mol Biol Cell.
26(8):1523-31. doi: 10.1091/mbc.E14-12-1613. PMID:25694446
d. Cox, C.M., Mandell, E.K., Stewart, L., Lu, R., Johnson, D.L., McCarter, S.D., Tavares, A., Runyan, R.,
Ghosh, S., Wilson, J.M. 2015. Endosomal regulation of contact inhibition through the AMOT:YAP
pathway. Mol Biol Cell 26:2673-84. doi: 10.1091/mbc.E15-04-0224 PMID:25995376
3. Cell Polarity
A feature required for cells to carry out their specialized functions, be it epithelial cells, neurons, or migrating
fibroblasts, is the ability to form specialized membrane domains, i.e. to polarize. In our studies of polarity, we
found that small GTPase-mediated regulation of membrane trafficking and the cytoskeleton is essential for
the development of polarized membrane domains. In addition, dynamic interactions of polarity complexes
that are associated with tight junctions are also essential for the polarized phenotype. I was the Principal
Investigator who directed the studies of small GTPases, and was a collaborator on the study of polarity
complexes in neurons.
a. Hernandez-Deviez, D., J.E. Casanova, and J. M. Wilson. 2002. Regulation of dendritic development
by the ARF exchange factor ARNO. Nature Neurosci. 5:623-624.
b. Hernandez-Deviez, D., J.E. Casanova, Roth, M.G., and J. M. Wilson. 2004. ARNO and ARF6 regulate
axonal elongation and branching through phosphatidylinositol 4-phosphate 5-kinase a.Mol. Biol. Cell
15:111-21.
c. Kitt, K.N., D. Hernandez-Deviez, S. McCarter, E. Spiliotis, J.E. Casanova, and J.M. Wilson. 2008.
The small GTPase Rab 14 regulates apical targeting. Traffic 9:1218-1231
d. Parker, S.S., E.K. Mandell, S.M. Hapak, I.Y. Maskaykina,Y. Kusne, J.Y. Kim, J.K. Moy, P.A. St. John,
J.M. Wilson, K.M. Gothard, T.J. Price, S. Ghosh. 2013. Competing interactions of PKMζ
and
aPKCλ
with the Par complex regulates polarity. Proc Natl Acad Sci USA 110:14450-5.
PMCID:PMC3761571
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/jean.wilson.1/bibliography/45925859/public/?sort=date&direction=a
scending.
D. Research Support
Ongoing
5R01 DK084047-05 (Wilson, PI)
07/01/11-06/30/16
NIH/NIDDKD
Regulation of Intestinal Tight Junction Structure by Membrane Traffic
This funding provides support for our studies on the role of the endosomal protein endotubin and the small
GTPase Rab14 in the establishment and maintenance of epithelial tight junctions. We are examining the role
of polarized membrane traffic in tight junction integrity and how these events control epithelial permeability
and barrier integrity.