Request for Funding
Medical Student Research Fellowship for Summer 2011

All descriptions must contain enough detail to permit an assessment of the problem that is to be addressed and the methodologies that are to be employed. Please be careful to outline the role that the student will play in the project that is described. Please ensure that all relevant approval numbers (IRB, IACUC) are provided.

Mentor:           Hsieh, Jer-Tsong    
Department:  Urology        
Room number: J8-134       
Mail Code:     9110  
Phone number:        8-3990
E-mail:           jt.hsieh@utsouthwestern.edu      
Project title:   The role of DAB2IP in aggressive prostate cancer       

Human subjects IRB approved project number (where applicable): N/A

Animal subjects IRB approved project number (where applicable):  2010-0260

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects) Basic Research

Brief Description of Project:

From the clinical outcome of prostate cancer (PCa), the presence of lymph node invasion has the lowest rate of 10-year progression-free survival rate. Thus identifing molecular marker(s) for predicting aggressive PCa and developing targeted therapy should prevent the onset of PCa metastasis and further reduce the mortality and morbidity rate of this disease. A recent study reported that a single nucleotide polymorphism (SNP) probe (i.e., RS1571801) has the highest predictive value for the risk of aggressive PCa.  Interestingly, this probe is located in DAB2IP gene; DAB2IP (DOC-2/DAB2 interactive protein) was first identified as a new member of RAS-GTPase activating protein (RAS-GAP) family with growth inhibitory activity in PCa. Our recent data indicate that knocking down endogenous DAB2IP in immortalized normal prostate epithelial cells promoted their tumorigenicity along with increased stem cell phenotypes, indicating the presence of cancer-initiating cell (i.e., cancer stem cell, CSC).  Moreover, loss of endogenous DAB2IP also initiated epithelial-mesenchymal transition (EMT); tumor cells become highly metastatic in various lymph nodes from several orthotopic mouse models. EMT is initially recognized during several critical stages of embryonic development and has recently been associated with CSC development and cancer metastasis. Thus, we hypothesized that loss of DAB2IP initiates EMT leading to the acquisition of CSC in PCa.  We are planning to study molecular mechanism of DAB2IP in PCa

Previous Research Activities or Publications with Medical Students:
2005                           Kit Tam
2009                           Stephen Chiang
2010                           Stephen Chiang