Epigenomic and Transcriptomic Changes in the Onset of Disease

Current sequencing technologies allows researchers unprecedented insight into our biology, and how these biological mechanisms can become distorted and lead to disease. These aberrant mechanisms can be brought about by many causes, but some occur as a result of genetic mutations or external factors through the epigenome. Here, we used our microfluidic technology to profile the epigenome and transcriptome to study such aberrant mechanisms in three different diseases and illnesses: breast cancer, chronic inflammation, and mental illness. We profiled the epigenome of breast tissue from healthy women with the BRCA1 mutation to understand how the mutation may facilitate eventual breast cancer. Epigenomic changes in breast cells suggest that cells in the basal compartment may differentiate into a different cell type, and perhaps become the source of breast cancer. Next, we compared the epigenome and genome of murine immune cells under low-grade inflammation and acute inflammation conditions. We found that low-grade inflammation preferentially utilizes different signaling pathways than in acute inflammation, and this may lead to a non-resolving state. Finally, we analyzed the effect of the maternal immune activation on unborn offspring, and how these changes could cause later mental illness. The insights we made into these diseases may lead to future therapies.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Chemical Engineering

Department dc:contributor.department

Chemical Engineering

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2021

Author dc:creator

• Naler, Lynette Brigitte

Chair dc:contributor.committeechair

• Lu, Chang

Committee members dc:contributor.committeemember

• Tong, Rong
• Goldstein, Aaron S.
• Davis, Richey M.

• Epigenomics
• Transcriptomics
• Chromatin Immunoprecipitation
• RNA Sequencing
• Breast Cancer
• BRCA1
• Inflammation
• Lipopolysaccharide
• Maternal Immune Activation
• Cross-Fostering

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:30377

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/103388