Thesis Defense Announcement
To:  The George Mason University Community
Candidate: K. Alex Hodge

Program: M.S. in Biology



Date:   Wednesday, November 16, 2016

Time:   2:00 pm

Place:  IABR Lab Building, Room 1003
             George Mason University
             Science & Technology Campus<http://www.gmu.edu/resources/welcome/Directions-to-GMU.html>





Title: "Protein Network Mapping of Bladder Cancer: An Analysis of Tumor Compartment and the Surrounding Microenvironment"

Thesis Director: Dr. Emanuel Petricoin

Thesis Committee:  Dr. Kylene Kehn-Hall, Dr. Barney Bishop



All are invited to attend the defense.



Abstract:
The interaction between tumor and stroma has become of intense interest in the field of oncology in order to better understand the driving forces behind tumor onset and progression, metastasization and the responsiveness to therapy. These interactions are hard to capture using in vitro techniques and the extent to which in vivo models really recapitulate the tumor-stroma interactions of human tissues is still under investigation. For these reasons, human specimens still remain optimal input material for exploring these interactions. Laser capture microdissection (LCM) coupled with reverse phase protein microarrays (RPPA) are ideal technologies for isolating different cell compartments from heterogeneous tissues and for exploring protein signaling network of human tissue specimens.  This study explored the protein signaling network of 23 bladder cancers within the epithelium and the surrounding stroma across different histotypes including normal, carcinoma in situ (CIS), papillary, and invasive cellular compartments.  Pure tumor epithelium and surrounding stroma were first isolated with LCM followed by RPPA that allows for the measurement of hundreds of proteins and phosphoproteins. The analysis of the epithelium compartments collected from patients affected by papillary and invasive cancer revealed different pathway involvement driving the tumor, with invasive cases showing a phenotype of proliferation and survival in contrast to papillary tumors which was characterized by wound healing and metabolism. While the stroma surrounding both invasive and papillary tumors showed high correlation between the different members of the PI3K/AKT pathway, only invasive tumors presented with interconnection between proteins involved in the immune response.  Receptor tyrosine kinases (RTKs) in the epithelium appeared to be highly correlated with RTKs in the stroma as well as their downstream targets suggesting a cross-talk between the two.

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