التفاصيل البيبلوغرافية
| العنوان: |
The Impact of Oncogenic Signaling on Metabolic Stress Responses and Human Cytomegalovirus Infection |
| المؤلفون: |
Munger, Joshua, Xu, Shihao |
| بيانات النشر: |
University of Rochester School of Medicine and Dentistry |
| سنة النشر: |
2018 |
| المجموعة: |
University of Rochester, New York: UR Research |
| مصطلحات موضوعية: |
Ras, SV40 T antigens, Metabolic stress, Fatty acid biosynthesis, Cytomegalovirus, Viral restriction |
| الوصف: |
Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Biochemistry and Biophysics, 2016. ; Viral oncoproteins and cellular mutations drive malignant transformation. These oncogenic alterations induce metabolic changes and dependencies that can be targeted to kill cancerous cells. In my first project, we find that oncogenic Ras expression activates fatty acid biosynthesis and confers sensitivity to fatty acid biosynthetic inhibition in human fibroblasts. In addition, we find that a human breast cancer cell line harboring an oncogenic Ras mutation is more sensitive to fatty acid biosynthetic inhibition relative to a non-transformed human breast epithelial cell line (MCF10A). To further explore the impact of specific oncogenic alleles on epithelial cells, we created isogenic MCF10A cells expressing oncogenic Ras. Our data show that oncogenic Ras expression increases fatty acid biosynthesis and sensitizes MCF10A cells to fatty acid biosynthetic inhibition without increasing cellular proliferation. Together, our results indicate that oncogenic Ras confers sensitivity to fatty acid biosynthetic inhibition in human fibroblasts and epithelial cells. This oncogene-induced sensitivity may make an attractive target for therapeutic intervention. In my second project, we investigated the mechanisms that restrict human cytomegalovirus (HCMV) replication in cancerous cells. These mechanisms of viral restriction represent vulnerabilities that could be therapeutically exploited in other contexts. We explored these mechanisms by determining whether defined oncogenic alleles could inhibit HCMV replication. We find that expression of the SV40 T antigens (TAg) blocks HCMV infection in human fibroblasts. The earliest restriction of HCMV infection involves a block of viral entry. Subsequently, we found that TAg expression reduces the abundance of platelet-derived growth factor receptor α (PDGFRα), a host protein important for HCMV entry. Viral entry into TAg-immortalized fibroblasts could largely be ... |
| نوع الوثيقة: |
thesis |
| وصف الملف: |
Number of Pages:xviii, 166 pages; Illustrations:some color |
| اللغة: |
English |
| العلاقة: |
http://hdl.handle.net/1802/31389Test |
| الإتاحة: |
http://hdl.handle.net/1802/31389Test |
| رقم الانضمام: |
edsbas.E80069E4 |
| قاعدة البيانات: |
BASE |
