CBR Research Grants
Project Summaries—2005
2005 |
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2005Surface -Engineered Implantable Materials for Hernia Repair This program will develop an implantable biomaterial for hernia repair whose surface properties elicit appropriate physiological responses: Long term adhesion to and / or ingrowth of abdominal wall connective tissue on some areas and bio-inertness (lack of adhesion, ingrowth, or immunoreaction) on others. This will be achieved by surface modification of polypropylene, a material already used for hernia repair: Its mechanical properties work well in the abdomen, but its native surface properties often cause complications. The strategy for bio-inert regions of the implant will be to develop robust polyethylene oxide (PEO) brushes. While PEO-surfaces often work well in-vitro in on model surfaces, both in-vitro and in-vivo studies indicate medium to poor performance with PEO treatments on “real” implantable materials. Brush-covered micron-sized vesicles, however, are biocompatible in rats. The proposed work therefore hypothesizes that the prior problems with PEO layers on “real” surfaces stemmed from inadequate “brush” formation, and the study will go forward to develop chemistries appropriate to polypropylene that will produce brushes that are truly bio-resistant. Separately for surfaces designed to promote tissue ingrowth, the study will compare hydrophobic adhesive surfaces to those that are collagen-coated. The proposed work will be carried out jointly in the Santore lab at UMass and in the animal (swine) facility at Baystate under the supervision of Dr. Earle. While PEO-surfaces have been a topic of fundamental study, this work will be their first use for hernia-repair materials. Effective date: September 1, 2005 Male Factor in Infertile Couples: a Molecular Approach Mammalian sperm are not able to fertilize eggs immediately after
ejaculation. They acquire fertilization capacity after residing
in the female tract for a finite period of time. The physiological
changes occurring in the female reproductive tract rendering the
sperm able to fertilize constitute the phenomenon of " sperm capacitation ".
Using the mouse as an experimental model, it has been demonstrated
that capacitation is associated with an increase in the tyrosine
(tyr) phosphorylation of a subset of proteins.
The presence of this regulatory pathway has subsequently been demonstrated
in sperm from other species including human. After capacitation,
sperm are ready to fertilize the egg; during fertilization, the
sperm induces in the egg a series of changes in intracellular calcium
concentration ([Ca 2+ ]i), [Ca 2+ ]i oscillations ,
that initiate egg activation. Although the precise mechanism by
which the sperm initiates these oscillations is not known, there
is evidence suggesting that the sperm may deliver, after fusion,
a factor(s) into the egg cytosol that is responsible for triggering
Ca 2+ release. This factor from the sperm appears to mediate Ca
2+ release by persistently activating the phosphoinositide (PI)
pathway and is believed to be phospholipase C z (PLC z), a
novel sperm-specific PLC. Effective date: September 1, 2005 TILs in high grade breast tumors: role of Notch signaling Lymphocytes and other immune cells are involved in normal mammary
gland development, as well as the pathogenesis to breast cancer.
While the immune system is often associated with anticancer activity,
immune cells can also enhance the secretion inflammatory cytokines
and enzymes which promote invasion and angiogenesis. Many tumor
infiltrating immune cells often possess a suppressive capability
as well which can shut down the responses of other lymphocytes.
The mechanism by which tumor cells subvert immune function to promote
the progression to cancer is unknown. Effective date: September 1, 2005 Misregulation of Acheron Expression in Human Rhabdomyosarcoma Rhabdomyosarcoma (RMS) constitutes one of the most prevalent childhood
soft tissue tumors, accounting for more than 50% of pediatric sarcomas.
RMSs are derived from cells of a skeletal muscle-specific lineage
at an early point in differentiation. These tumors express the
muscle-specific transcription factor MyoD and many have histological
similarity to developing fetal skeletal muscle but fail to differentiate.
Not surprisingly it has been demonstrated that the metastatic potential
of RMS is inversely related to the degree of differentiation. In
fact, one key goal in RMS research is to identify factors that
can facilitate RMS differentiation into mature skeletal muscle. |
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