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Rebecca Wells
Assistant Professor, Depts of Medicine and Pathology and Laboratory
Medicine
Cell Biology and Physiology
Program
Address
664 Clinical Research Building (Office)
670 Clinical Research Building (Lab)
415 Curie Blvd
Philadelphia, PA 19104
Office tel.: 215 573-1860
Lab tel.: 215 573-1881
Fax: 215 573-2024
E-mail: rgwells@mail.med.upenn.edu
Link(s)
Dr.
Wells's Gastroenterology Research Summary
EDUCATION
Yale University: BS (Molecular Biophysics and Biochemistry),
1983.
Johns Hopkins University School of Medicine: MD (Medicine),
1987.
The Whitehead Institute for Biomedical Research: Postdoctoral
Research (TGF-ß receptor biology), 1990-1995; 1996-1998.
Brigham and Women's Hospital: Postdoctoral Research (Amino
acid transporters), 1990-1992.
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RESEARCH INTERESTS
- TGF-ß receptor biology
- Hepatic stellate cell function in liver fibrosis
Key words: Hepatic
stellate cells, TGF-ß receptors, liver fibrosis, betaglycan,
TGF-ß.
Search PubMed for articles
DESCRIPTION OF RESEARCH
My laboratory is interested in liver fibrosis and in
the mechanical and soluble factors (especially TGF-ß) that regulate
liver fibrosis and the phenotype of fibrogenic cells in the liver.
These projects involve close collaborations with groups in Bioengineering
and at Children's Hospital, as well as at other institutions.
The major projects in my laboratory are:
- The study of liver cell fibrogenesis. We have previously
demonstrated that TGF-ß acting via its downstream intermediate Smad3 regulates
stress fiber formation in some of the major fibrogenic cell types of the liver.
We are now examining the interaction between focal adhesions and stress fibers
in different liver cell populations, and are determining the functional correlates
of these differences (in particular contractility). Additionally, we are studying
the role of fibronectin splice variants in regulating the phenotype and function
of potentially fibrogenic cells in the liver, and are studying the role of signal
transduction pathways regulated by the different splice variants.
- The study of the type III TGF-ß receptor betaglycan. We have
previously demonstrated that the role of this receptor varies depending on cell
type specific glycosaminoglycan modifications. We are currently investigating new
functions for its cytoplasmic domain and suggest that regulation of the cleavage
and phosphorylation of the cytoplasmic domain may have important implications for
understanding TGF-ß signaling.
- Studying the role of mechanical factors on the development of
liver fibrosis. We have previously demonstrated that matrix stiffness determines
whether or not cells of the liver adopt a fibrogenic phenotype. Ongoing work is
focused on a) identifying the mechanotransducers and b) determining whether mechanical
changes are relevant to the development of fibrosis in vivo. As part of our in vivo
studies, we are examining the role of collagen cross-linking in the development of
disease.
- The role of EMT in liver fibrosis. We have preliminary evidence
that biliary epithelial cells undergo the epithelial to mesenchymal transition in
certain kinds of liver fibrosis. Current work is focused on lineage tracing
experiments in genetically engineered mice to demonstrate definitively (and
quantitatively) the contribution of EMT to fibrosis, and to identify relevant
signaling pathways.
RECENT PUBLICATIONS
Li Z., Dranoff J.A., Chan E.P., Uemura M., Sévigny
J., Wells R.G.. (2007). TGF-ß and substrate
stiffness regulate portal fibroblast activation in culture.
Hepatology. (in press).
Díaz R., Kim J.W., Hui J.J., Li Z., Swain G.P., Fong
K.S.K., Csiszar K., Russo P.A., Rand E.B., Furth E.E., Wells
R.G.. (2007). Evidence for the epithelial to mesenchymal transition
in biliary atresia fibrosis. Human Pathology. (in
press).
Uemura, M., Swenson, E.S., Gaça, M.D.A., Reiss,
M., Giordano, F.J., Wells, R.G.. (2005). Smad2 and
Smad3 play different roles in rat hepatic stellate cell function
and a-smooth muscle actin organization, Mol. Biol. Cell.
16, 4214-24.
Wells, R.G. (2005). The role
of matrix stiffness in hepatic stellate cell activation and
liver fibrosis. J Clin Gastro. 39, S158-S161.
Eickelberg, O., Centrella, M., Reiss, M., Kashgarian,
M., Wells, R.G.. (2002). Betaglycan inhibits
TGF-ß signaling by preventing type I-type II receptor complex
formation. Glycosaminoglycan modifications alter betaglycan
function. J. Biol. Chem. 277, 823-9.
Lab
Rotation Projects:
- There are several; please speak with PI.
- Personnel:
- Zhaodong Li, M.D., Postdoctoral Fellow
Erick Chan, M.D., Postdoctoral Fellow
Rosalyn Diaz, M.D., Postdoctoral Fellow
Jia-Ji Hui, M.D., Research Specialist
Cheyne Blair, PhD, candidate
Abby Olsen, MD/PhD, candidate
Kandice Johnson, PhD, candidate
Mia Maamari, Lab Technician
Ji Won Kim, Medical student
last updated 7/2007
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