Download Aminoacyl-tRNA Synthetases (AARS) Inventor: Overview Invention

Aminoacyl-tRNA Synthetases (AARS)
Novel Targets for Therapeutics Directed Against Cancer and Autoimmune Disease
Inventor: Christopher Francklyn and Karen Lounsbury
The University of Vermont, Office of Technology Commercialization
Overview
All living cells carry out protein synthesis, a
process that requires tRNA adaptors as part of
genetic coding. Amino acids are added to the
these tRNA adaptors in a chemical reaction
catalyzed by aminoacyl-tRNA synthetases
(AARSs). Our work on these enzymes
currently focuses on the histidyl- and threonyltRNA synthetases, with others under
development. In particular, our studies focus
on their structures, their mechanisms, and
their exploitation as targets for both
therapeutic and biotechnological applications.
An emerging theme in protein structure and
enzymology is the recruitment of enzymes
from one family to carry out novel functions
that are distinct from those of the parent
members. In the last 2-3 years we discovered
additional unique roles for these enzymes in
human diseases, including an association of
human histidyl-tRNA synthetase with Type
3B Usher syndrome and threonyl-tRNA
synthetase with various forms of metastatic
cancer. Our current work is following up these
initial discoveries.
Invention
The invention comprises several key findings.
First, it constitutes a method for increasing
angiogenesis in a subject by administration of
Threonyl-tRNA synthetase (TARS) which acts
as a pro-angiogenic chemokine-like protein. In
cell models, TARS efficiently stimulates new
blood vessel formation. The use of TARS and
TARS activators is different from existing
technologies, as this pathway was unknown
before our discovery.
Secondly, A class of compounds (borrelidin and
its derivatives), that inhibit TARS, and modulate
angiogenesis, lead to changes in the expression
of vascular endothelial growth factor when
added to mammalian cells. TARS is secreted
from endothelial cells in response to cytokines,
and promotes angiogenesis in the extracellular
context by stimulating endothelial cell migration.
This unusual function can be blocked by small
molecules. Clinical observations suggest that
TARS is up regulated in prostate and ovarian
cancer, indicating that its pro-angiogenic
function may be physiologically significant.
These discoveries reveal a novel mechanism
whereby a critical protein in protein synthesis
(TARS) is involved in the regulation of the
growth of the vasculature, and this pathway is
important in metastasis.
Advantages
•
TARS is a novel biomarker with numerous
potential applications in cancer diagnosis. It
can be readily detected in human serum by
existing technologies.
Applications
•
Increasing angiogenesis in patients with
cardiovascular disease, wound healing, and
other conditions where increased vasculature
is desirable.
•
Inhibiting angiogenesis and metastasis in
advanced cancer.
•
Potential utility in cancer diagnostics, and
monitoring of the effectiveness of cancer
treatments.
Patent Status
Patent Applications Filed
Worldwide Rights Available
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Learn more about Dr. Francklyn's & Dr.Lounsbury’s
research at:
http://biochem.uvm.edu/francklyn-lab/
http://bit.ly/1i4gDmA
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contact us at: Ph: 802-656-8780 or email:
[email protected]
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