Author ORCID Identifier


Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Cancer Biology

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Pawel K. Mazur, PhD

Committee Member

Junjie Chen, PhD

Committee Member

Anirban Maitra, MBBS

Committee Member

Di Zhao, PhD

Committee Member

Jae-Il Park, PhD

Committee Member

Michael Kim, MD, FACS


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.

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).

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.

Together, this work elucidates the role of NSD3 in tumorigenesis and provides a rationale for this KMT as an actionable for neuroendocrine tumors.


Mouse models of cancer, neuroendocrine tumors, epigenetics, transcriptional programming in cancer

Available for download on Saturday, April 26, 2025