Active Awards 1. T32 GM-08721-09 (NIH/NIGMS)
7/1/99-6/30/09 $111,760 (direct costs, 07-08)
Lyle L. Moldawer, Ph.D. (Principal Investigator)
"Molecular Biology and Gene Therapy in Burns and Trauma"
A training grant to provide surgical residents with a two year
research experience in the laboratory of an established molecular
biologist and gene therapist M.D. candidates are expected to
complete a didactic training program with extensive bench research
in the laboratory of a funded basic scientist to develop expertise
in molecular biology and gene therapy methodologies.
Opportunities to complete an M.S. degree in clinical science, or a
Ph.D. degree are also available.
2. U54 GM-62119-05, (NIH/NIGMS)
09/30/01-9/29/10 $6,599,869 (direct 01-02)
Ronald Tompkins, M.D. (Principle Investigator) Lyle
Moldawer,Ph.D.
(Steering Committee, P.I. Proteomics Core)
$287,479(direct
costs 07-08)
"Inflammation and the Host Response to Injury"
This large scale collaborative project involves 43 investigators
nationally, and is aimed at using high throughput genomics and
proteomics to determine gene expression and protein expression
patterns in trauma and burn patients to identify patients who will
succumb to multisystem organ failure. The Laboratory of
Inflammation Biology and Surgical Science serves as the Sample
Collection and Coordination Site for the project, as well as an
analytical site in the Genomics Core and the Protein Analysis and
Cell Biology Cores. For more information regarding the
program, see www.gluegrant.org.
3. R01 GM-63041-05 (NIH/NIGMS)
04/01/01-07/31/09
$181,340 (direct costs 07-08)
Lyle L. Moldawer, Ph.D. (Principal Investigator)
"Targeted Interleukin-10 Gene Therapy in Sepsis Syndromes"
This application proposes to explore the utility of adenovirus-based gene therapy
as a an anti-inflammatory and anti-apoptotic agent for the treatment
of sepsis syndromes. Two approaches are included. Targeted
expression of anti-inflammatory and anti-apoptotic genes by
dendritic cells can alter their phenotype, and dramatically change
the interactions between the innate and acquired immune system,
through the generation of unique regulatory T-cells. Targeting
dendritic cells both ex vivo and in vivo has become a major focus of
the current program. In addition, by targeting epithelial
cells in the liver and lung, adenoviral delivery of
anti-inflammatory genes like IL-1 and NF-KB super can alter the
balance between pro- and anti-inflammatory cytokines in these local
tissue environments.
4. R01 GM081923-01A1 (NIH/NIGMS)
5/01/08 - 02/28/12 $180,000 (direct costs 07-08)
Lyle L. Moldawer (Principal Investigator)
“Myeloid Suppressor Cells in Sepsis and Trauma”
This is a new application intended to explore the contribution of
immature myeloid cell populations to the immune suppression
associated with sepsis syndromes. Using murine models of sepsis (cecal
ligation and puncture) the investigators are exploring the mediators
that drive the expansion of this unique cell population during
chronic sepsis. Using genetic and pharmacologic approaches to block
the expansion of this cell population, the studies are aimed at
elucidating the role that these cells play in sepsis.
5. R01 DK066211-01A2 (NIH/NIDDK)
10/01/05 - 09/30/10 $250,000 (direct costs 05-06)
Kevin E. Behrns, M.D. (Principal
Investigator)
Lyle L. Moldawer (Co-Investigator)
"Growth Control of Normal and Cirrhotic
Hepatocytes"
The major aim
of this proposal is to continue previous work that examines mechanisms
of apoptosis resistance in murine cirrhotic hepatocytes. This
proposal will focus differences in signal mechanisms of transforming
growth factor beta-induced apoptosis in normal and cirrhotic
hepatocytes.
6. Action Pharma A/S
09/01/07 – 02/28/09 $ 275,346 (total direct costs)
Thomas M. Beaver, M.D. (Principal Investigator)
Lyle L. Moldawer (consultant)
A Phase IIA, FDA regulated clinical trial examining the impact of
prophylactic treatment with AP214 on the proinflammatory interleukin
response and postoperative renal function in patients with coronary
artery bypass grafting. Dr. Moldawer is only a consultant on this
project and has no formal time allocated to the project. The direct
costs identified above are for the purchase of gene chips, and flow
cytometry reagents to phenotype blood neutrophil and monocyte
populations in patients after coronary bypass surgery who have been
randomized to either a placebo or an anti-inflammatory MSH analogue.
Dr. Moldawer is providing mentorship and consulting services to the
principal investigator.
7. TEI Biosciences, Inc. 10/01/07 –
9/30/08 $ 16,311 (total direct cost)
Lyle L. Moldawer, Ph.D. (Principal Investigator)
“Proposed Pilot Study for SurgiMend™"
Acellular skin substitutes are increasingly being used to
correct ventral hernias and provide a scaffold in reconstructive
surgery. Yet little is known about how host cellular populations
infiltrate these skin substitutes and what role inflammation plays
in their long-term acceptance. Using a rat model of ventral hernia,
the investigators are implanting different skin substitutes
subcutaneously, and evaluating celluiar infiltration and
inflammation using immunohistochemical, biochemical and genomic
approaches. The goal is to characterize the inflammatory response to
these skin substitutes and to map the cellular processes that occur.
Once this baseline information is obtained, subsequent studies will
be proposed and conducted with modified skin substitutes.
PENDING 1. R37GM-40586-14 (NIH/NIGMS)
RENEWAL PENDING
08/01/88-11/30/07 $195,190 (direct costs 04-05)
Lyle L. Moldawer, Ph.D. (Principal Investigator)
"Cytokine Regulation in Sepsis and Inflammation"
The overall goal of
this award is to examine proinflammatory cytokine, cytokine inhibitor
and anti-inflammatory cytokine regulation in sepsis, and bacterial
infections. Using rodent models of a cecal ligationa and puncture, or
endotoxemia, the application intends to explore the role of TNF
signaling pathways in determining outcome to sepsis and endotoxemic
shock.
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