Discovery Park Undergraduate Research Internship Program

"Analysis of chromatin in breast differentiation and cancer"

About the Project

Project Time & Type:
Fall 2011 - DURI
Research area(s):
cell biology, epigenetics
Project Description:
The aggressive triple negative breast cancer (TNBC) defined by the absence of estrogen, progesterone and HER2 receptors expression is difficult to treat due to high recurrence rate, distant metastasis and poor survival rate. Studies have shown that the TN-basal like carcinoma in situ (CIS) has a high percentage of the population of CD44+/CD24- stem cells, which progressively decreases as cancer progresses. Differentiation of stem cells has been proposed for this decrease and disease progression. The chromatin-binding protein LEDGF has been implicated in the differentiation of neuroepithelial stem cells including lens progenitor cells and is absent in terminally differentiated lens fiber cells. LEDGF also confers protection to cells against thermal and oxidative stress with the latter linked to differentiation of stem cells. Preliminary studies from the HMT-3522 breast cancer progression series and other TN breast cancer invasive cells in our laboratory have indicated that LEDGF protein level either decreases or is barely detectable as the cancer progress. Furthermore, the mRNA levels of LEDGF appear to be down-regulated in different TN breast cancer invasive and noninvasive cells compared to non-neoplastic cells. Based on the down-regulation of LEDGF expression in TN breast cancer invasive cells we propose that LEDGF alterations accelerate cancer progression either by promoting cancer stem cell differentiation or by not preventing the control of oxidative stress. To study the impact of LEDGF on cancer progression possibly via stem cells, we propose to look at the association between LEDGF and cancer stem cells in different stages of cancer progression. We will also collaborate with Dr. Joseph Irudayaraj at Purdue University to use a microscopy-based single molecule analysis technique to investigate the epigenetic environment of the cancer stem cells. Finally we will investigate the oxidative stress-induced effects on LEDGF expression, stem cell differentiation and cancer progression.
Expected Student Contributions:
The intern will work with a graduate student on specific aspects related to LEDGF and also chromatin organization in general. She/he will be trained to design, perform and analyze experiments and will have the possibility to present at local meetings.
Related Website(s):
Desired Qualifications:
Those requested by DURI
Estimated Weekly Hours:
Department awards independent research credits for this project?
Yes, 3 credit hours

Professor in Charge

Lelievre, Sophie
basic medical sciences

Student Supervisor

Sophie Lelievre
Associate Professor

Cooperating Faculty

Joseph Irudayaraj
Agricultural and Biological Engineering/Agricultur