Cardiovascular Targets
Thrombosis formation
is a chief health concern
worldwide as it leads
to significant patient
morbidity and mortality.
The creation of efficient
and specific inhibitors
of blood coagulation
remains critical to the
appropriate clinical
management of thromboses.
Heparin, a highly sulfated
polysaccharide isolated
from mast cells, has
been the preferred anticoagulant
and antithrombotic agent
for more than seven decades.
The rational design of
low molecular weight
heparins (LMWH) with
improved in vivo activity
is at the forefront of
our R & D program.
Pulmonary System
Although heparin and
LMWHs have been widely
used in treatment as
anticoagulants, their
broader use has so far
been limited by a lack
of non-invasive delivery
methods for this class
of molecules. Our laboratory
has demonstrated an efficient,
rapid, and reproducible
delivery system for heparin
through the lungs that
is not constrained to
particles of a certain
geometric or aerodynamic
diameter.
Oncology
Cell surface and ECM
glycans regulate nearly
all aspects of cancer
biology—including
tumorigenesis, tumor
progression, and metastasis.
A particular tumor-derived
glycan can be pro-tumorigenic
or anti-tumorigenic,
largely depending on
fine glycan structure.
Recent evidence has highlighted
the fact that, as part
of the transformation
process, cancer cells
alter their cell-surface
glycome profile. This
change includes the differential
expression of particular
proteoglycan-core sequences,
and the alteration of
GAG fine structure of
consitutent proteoglycan
chains. Communicative
cross-talk in the tumor
microenvironment, which
is central to oncogenic
activity, is largely
regulated, and thus could
potentially be manipulated,
via glycan biomolecules. |
Neurobiology
Oligosaccharide chains
of a nervous system origin
influence a wide array
of biological processes.
Through these same processes,
glycans play an essential
role in neural development.
Perhaps the most provocative
evidence for the key
role of complex polysaccharides
in neural development
are recent findings demonstrating
that these sugars are
critical in cytokinesis
and morphogenesis during
the early embryonic stages
of the nematode, Caenorhabditis
elegans. Futhermore,
glycans have also been
implicated as a major
deterrent to the regeneration
of axons following traumatic
injury to the brain and
spinal cord. Such injuries
typically result in paralysis
and the chances for recovery
for spinal cord injury
patients are infinitesimally
small. Our group is exploring
various glycan-based
strategies geared towards
alleviating these conditions.
Biotherapeutics
Glycan-based strategies
for drug development
fall into two main categories:
restorative therapies
and interventions. Restorative
therapies seek to replace
biomolecules that the
body fails to synthesize
adequately. Drugs that
can intervene in glycan-dependent
disease processes represent
a novel niche for drug
discovery research, where
the manipulation of molecular
interactions holds the
promise of improving
patient outcomes. |
