University of Texas Health Science Center at Houston
HISTONE LYSINE METHYLTRANSFERASE NSD3 GOVERNS TRANSCRIPTIONAL PROGRAMS THAT DRIVE PANCREATIC NEUROENDOCRINE TUMORS (PANNETS)
Abstract
dc:description.abstract<p>Pancreatic Neuroendocrine Tumors (PanNETs) are the most common and lethal neuroendocrine malignancies where treatments used in advanced patients have limited efficacy, adverse side effects, and acquire resistance. Thus, there is a critical need to uncover novel precision therapeutics for PanNET patients. Additionally, pre-clinical models that more accurately represent disease are an urgent necessity for translational studies.</p> <p>This dissertation directly addresses these challenges by identifying histone lysine methyltransferase (KMT) NSD3 as a critical oncogenic driver of PanNETs through di-methylation of histone H3K36 (H3K36me2).</p> <p>The findings shown in this body of work indicate that H3K36 methylation by NSD3 functions as a transcriptional activator accelerating tumorigenesis in PanNETs. Additionally, we established a novel genetically engineered mouse model (GEMM) for PanNETs focused on the top inactivating mutations observed in human disease. Lastly, we have identified therapeutic vulnerabilities of NSD3 that target growth-signaling pathways and bromodomain inhibition rendering tumor growth in vitro.</p> <p>Together, this work elucidates the role of NSD3 in tumorigenesis and provides a rationale for this KMT as an actionable for neuroendocrine tumors.</p>
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy (PhD)
- Level thesis:degree_level
- Dissertation (PhD)
- Year dc:date.available
- 2024
Author and committee
dc:creator, dc:contributor.*- Authors dc:creator
-
- Fuentes, Mary Esmeralda
- <p><a href="https://orcid.org/0000-0002-8044-2313">0000-0002-8044-2313</a></p>
- Contributors dc:contributor
-
- Pawel K. Mazur, PhD
- Junjie Chen, PhD
- Anirban Maitra, MBBS
Subjects
dc:subject × 7Identifiers
dc:identifier.*- Repository record dc:identifier
- https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1356
- OAI identifier oai:identifier
- oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2414