Dissecting nuclear protein dynamics and structural changes with single-molecule spectroscopy and microscopy

Cancer is one of the most significant causes of mortality in the United States, with approximately 1 in 4 individuals likely to develop cancer during their lifespan. Unfortunately, despite the enormous effort in cancer diagnosis and therapy, the mortality rate is still high because of multiple challenges imposed by cancer relapse, metastasis, and drug resistance. The origin of such tragedy lies in the heterogeneity of tumors featuring various cellular morphology, genomics, and epigenomics. Tumor heterogeneity is linked with genetic mutations, epigenetic alterations, and external pressure from the tumor microenvironment. Biochemical approaches such as next-generation sequencing can elucidate the genetic origins of heterogeneity. Recent literature has shown that epigenetic modifications play a prominent role in modulating transcription, yet limited knowledge exists in the mechanistic understanding of such changes in the context of living cell. Understanding how epigenetic modifications affect the state of chromatin and discovering phenotypical epigenetic states are critical for advanced cancer detection and treatment. This work evaluated how external cues, such as environmental toxicants, pharmaceutical drugs, and tumor microenvironment, could affect chromatin and its dynamic states with single-molecule fluorescence tools in living cells. To develop a mechanistic basis, single-molecule tools were used to track and identify cells that exhibit phenotypical epigenetic traits, linking specific epigenetic modifications in response to drug treatment and tumor progression.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Liu, Wenjie

Contributors dc:contributor

• Irudayaraj, Joseph
• Cunningham, Brian
• Underhill, Gregory
• Bhargava, Rohit

• epigenetics
• single-molecule

Statement dc:rights

• Copyright 2022 Wenjie Liu

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/116033

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F116033