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RESEARCH |
PLASTIC & RECONSTRUCTIVE SURGERY
The
Plastic Surgery Research Laboratory
The Research Lab is part of the Division
of Plastic & Reconstructive
Surgery, interacting with several
of the Division's faculty. This laboratory
has been in existence for more than twenty-five
years and has received continual NIH
funding since its inception. The Plastic
Surgery Research Laboratory has an established
reputation for making significant contributions
in the area of normal and pathologic
wound repair. Members of the laboratory
actively collaborate with other members
of the Department of Surgery who are
studying similar processes.
Our Mission
The mission
of the Plastic Surgery Research Laboratory
is to provide a setting for the investigation
of the underlying mechanisms involved
in tissue injury and more importantly,
the process of tissue repair.
Priorities
of the Plastic Surgery Research
Laboratory include:
providing an intense
fertile setting that is conducive to
the training of young physician scientist
and,
to focus on productive
research projects that can be quickly
translated from the bench to the bedside.
Research Interests
Research interests in the Plastic Surgery
Research Laboratory fall into three major
areas:
One
focus is to investigate
the role of an over-exuberant neutrophil
response in the pathophysiology of
chronic wounds. Neutrophils are a source
of large amounts of proteases and oxidative
products that provide protection from
invading pathogens. However, when present
in excessive amounts, these same proteases
and oxidants can also cause tissue damage.
This laboratory has demonstrated that
chronic non-healing wounds contain elevated
levels of neutrophil proteases (e.g.,
collagenase-2 and elastase) and diminished
levels of endogenous inhibitors of these
proteases. These observations have led
to a collaborative effort with the Southern
Regional Research Center of the U.S.
Department of Agriculture to design new
types of dressings with the goal of controlling
the proteolytic and oxidative environment
of chronic wounds. Several questions
remain to be answered. Can the numbers
of neutrophils that enter a would site
be controlled? Can the activity of neutrophils
at a wound site be regulated? Can the
activity of neutrophil products be modulated?
Are neutrophil-derived oxidative species
involved in regulating gene expression
of cells present in the wound environment?
A
second focus involves determining the mechanisms
involved in wound contraction. Wound
contraction is the process by which
edges of a wound are drawn toward the
center. Though often a favorable occurrence
during repair, there are many instances
where this process becomes pathologic.
These include burn contracture, compression
contracture in cirrhosis, and post-surgical
stricture formation. To address questions
regarding contraction this laboratory
has developed a singularly unique model.
Open wounds in the fetal rabbit do
not contract. We have recently demonstrated
the ability of transforming growth
factor ß (TGF-ß) to induce contraction. This model is being used to dissect the mechanisms involv3ed in contraction. Using modern molecular biology and biochemical approaches, we are addressing the following questions. What genes are turned on or off in response to TGF-ß?
Is expression of these genes required
for the process of contraction? What
is the role of these genes? Can the
expression of these genes and hence
the process of contraction be controlled?
A
third focus is to determine the molecular and biochemical
details of hyaluronan synthesis. This
glycosaminoglycan is essential to development
and is associated with inflammation
and tumorigenesis. It is also believed
to play a major role in the "scarless" repair
of the fetal dermis. Using modern molecular
biology and biochemical approaches,
we are addressing the following questions.
Under what conditions are the different
hyaluronan systhases expressed? What
signaling pathways are used to regulate
hyaluronan expression? Can changing
the expression of the hyaluronan synthases
alter adult or fetal wound repair?
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