Regulation of Fibroblast Survival in the Collagen Matrix

DESCRIPTION (provided by applicant): The candidate is pursuing a career in
academic surgery as an Assistant Professor of Surgery at the University of
Nebraska Medical Center. His clinical interests include minimally invasive and
robotic surgery and surgery of the abdominal wall His basic science interests
include the regulation of wound healing, granulation tissue regression, and
tissue regeneration. He has completed a 6 year residency in general surgery
(Medical College of Wisconsin), a 1 year fellowship in minimally invasive
surgery (MCW), and a 3 year fellowship in basic research (wound healing) with
Fred Giinnell at the University of Texas Southwestern Medical Center. His
short-term goal is to establish, with the help of extramural funding, a career
in academic surgery at UNMC. His long-term goals include a greater
understanding of the healing mechanism, progress towards achieving tissue
regeneration, and advancement of minimally invasive and robotic surgery.
The UNMC Surgery Chairman hired the candidate with the intent that the
candidate would concentrate 75 percent of his efforts on research and career
development. The candidate?s career development plan involves a combination of
basic science research, didactic lectures, seminars, specialty courses,
scientific meetings, research presentations, and scholarly debate/discussions.
The candidate has 3 sponsors: a senior academic surgeon, a surgeon who is an
established wound healing investigator, and a cell biologist experienced in
apoptotic signal transduction. The latter two sponsors have NIH-funded
laboratories. The candidate foresees a 4 year period to perform the proposed
experiments and prepare an R01 application.
The candidate's research plan will investigate the regulation of fibroblast
survival in the collagen matrix. The clinical relevance is that since the
fibroblast is the primary cell involved with complications/untoward effects of
healing and scarring, control over fibroblast survival during healing should
allow the clinician to minimize the negative effects of scarring in select
clinical circumstances, such as in burn wound contracture, GI anastomotic
stricture, or cirrhosis. The candidate has hypothesized that matrix anchorage
upregulates focal adhesion kinase activity, which in turn upregulates the
PI3K/Akt survival pathway and inhibits the tumor suppressor p53, ultimately
promoting cell survival. Loss of matrix anchorage is hypothesized to reverse
these effects and induce apoptosis. The involvement of each protein will be
probed with mutated isoforms.