Indiana University-Purdue University Indianapolis (IUPUI) / The main focus of this study is to determine the impact of Set-Binding Factor 2
(SBF2) on human-derived neurons in the context of taxane-induced peripheral neuropathy.
Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many
cancer patients; SBF2 has been previously identified as a potential germline predictor that
has been found to be significantly associated with severe TIPN in African American (AA)
patients. The work described here provides ex vivo support for the use of SBF2 as a
genotypic biomarker to identify a priori which patients are at a higher risk of manifesting
severe TIPN.
This study demonstrates that diminished expression of SBF2 exacerbated the effect
of paclitaxel on viability and morphology and altered the functional response of a neuronal
model exposed to paclitaxel treatment. Furthermore, transcriptomic work showed that
reduced expression of SBF2 in a neuronal model treated with paclitaxel impacted the
expression of genes that modulate stress-induced cell death and pain threshold.
Altogether, these findings suggest that SBF2 plays a role in the development of
TIPN. This work sheds light on the pathways potentially involving SBF2 that can be
studied to further evaluate the function of this gene in neurons and its contribution to severe
TIPN. Further functional approaches investigating these pathways will be pivotal in
elucidating the underlying biological mechanism for this toxicity and identifying novel
targeted therapeutic strategies to prevent or treat TIPN. / 2021-05-17
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/26000 |
| Date | 05 1900 |
| Creators | Cunningham, Geneva Mari |
| Contributors | Schneider, Bryan P., Radovich, Milan, Liu, Yunlong, Skaar, Todd, Meyer, Jason, Ivan, Mircea |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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