Grants and Contracts Details
Description
Abstract
Cancer development often starts from small alterations in the development of central processes of multicellular
organisms and can include an increase in the number of cells, or slight differences in their division processes
and migration. Every cell has a system of communication that governs these basic cellular activities and
coordinates cell actions, i.e., its ‘cell signaling’ system. Errors during the process of signaling or
communications have serious consequences, including tumor formation and metastasis. By understanding cell
signaling, we will be able to treat all types of cancer more effectively.
Cell signaling is a complex network of interconnected signaling events that are coordinated by critical proteins
known as scaffolds. Scaffold proteins bring signaling partners into close proximity and help localize signaling
complexes to particular cellular locations. Our long-term goal is to understand the mechanisms by which
protein scaffolds orchestrate the regulation of particular signaling pathways in human cells as well as their role
in tumor progression. Towards this aim, our work currently focuses on analyzing the critical signaling scaffold,
Shoc2. Shoc2 functions as a platform that holds several signaling partners together, thereby allowing for
efficient signal transmission. To avoid errors of excessive or insufficient signal transmission, Shoc2 itself and
its signaling partners need to be controlled very precisely. We found that Shoc2 assembles intricate protein
machinery that in turn fine-tunes signals transmitted via the Shoc2 axis. Using a variety of complementary
approaches, we propose to identify and study cellular functions that are regulated by Shoc2-transmitted
signals, and in particular the cellular signals critical for tumor progression. Ultimately, we hope to translate this
knowledge into new therapeutic strategies for controlling invasive tumor cells.
In our work we use an innovative comprehensive approach encompassing genetic, state-of-the-art microscopy,
as well as advanced cell-based and biophysical methodologies. Of note, we use zebrafish as a vertebrate
model to investigate the physiological effect of Shoc2 gene editing on the early stages of development and
cancer growth because they offer distinct advantages for early developmental studies, including their
transparency, as well as their external and rapid development. Our studies are expected to produce an
ambitious and comprehensive mechanistic understanding of how Shoc2 is involved in determining the
specificity of tumor signaling outcomes, and has the potential for high impact by laying the groundwork for
future studies on the role of Shoc2 in cancer and contributing to the advancement of novel therapeutic
strategies and biomarkers.
Status | Finished |
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Effective start/end date | 8/1/21 → 8/1/23 |
Funding
- Markey Cancer Center Foundation: $50,000.00
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