Pathology Graduate Training Program
Name: Arlee Fafalios
Cellular and Molecular Pathology (CMP) -
Lab Phone: 412-623-3932
Mentor Name: Beth Pflug, Ph.D.
Name of school attended:Allegheny College
Undergraduate Major: Biology
Undergraduate degree: B.S. (2005)
Thesis Advisor: Dr. Beth R. Pflug
Thesis Title: Elucidating the Role of Translocator Protein in Prostate Cancer
Overall my research focuses on examining the molecular mechanisms involved in prostate cancer progression. In particular, I am interested in elucidating the role of Translocator Protein (TSPO) in prostate cancer. TSPO is a transmembrane molecule (also know as peripheral benzodiazepine receptor-PBR) that is best known for transporting cholesterol across the mitochondrial membrane for cell signaling and steroid biosynthesis. Overexpression of TSPO has been shown to contribute to pathologic conditions including cancer progression in several different models. Functionally, TSPO has been shown to take part in the regulation of apoptosis through its interactions with the mitochondrial permeability transition pore. TSPO is also involved in cell proliferation, as a correlation between TSPO expression and cancer cell proliferation has been observed in human astrocytomas and breast cancer while TSPO antagonism inhibits cell proliferation. Our preliminary studies demonstrate that TSPO is elevated in human prostate cancer and expression appears to increase with progression, as metastatic prostate cancer tissues have the highest expression levels. Additionally, we have shown that Lorazepam, a benzodiazepine commonly prescribed to treat anxiety disorders, inhibits prostate cancer cell growth and survival. Structurally, TSPO is 18-kDa in size and consists of 5 transmembrane domains. TSPO antibodies have identified immunoreactive proteins of higher molecular weight than the expected 18-kDa in cell and tissue extracts. Previous studies have suggested that these higher molecular weight bands are the result of dityrosine bonds that covalently link TSPO monomers. Our preliminary studies reveal 2 immunoreactive bands (18 & 36-kDa) in prostate cancer cell lysates and in vivo, we observed increased TSPO multimers in primary prostate cancer and metastatic lesions compared to normal prostate and matching unaffected sites. This data suggests that TSPO multimers may play a role in cancer and we will determine the regulation and function of TSPO multimers in cancer.
Awards - Undergraduate Honors:
- Presidential Scholar (2001-2005)
- Alden Scholar (2001-2005)
- Beta Beta Beta Biology Honor Society (2003-2005)