Research Highlights - Archives FY10

February 2010

Seed Funding Research Program Grant Awards

We congratulate the four investigators who received the first round of these awards.

Imad Shureiqi,M.D.
Role of PPAR-delta Overexpression in Colonic Tumorgenesis   *Video

Chongjuan Wei, Ph.D.
Novel use of the Niclosamide: Targeting mTOR Signaling in Peutz-Jeghers Syndrome    *Video

Xiaochun Xu, M.D., Ph.D.
Preclinical Chemoprevention of Esophageal Adenocarcinoma

Yuanqing Ye, Ph.D.
Predicting the Link of Developing Lung Cancer: A Multigenic Statistical Approach to MicroRNA   *Video


Role of PPAR-delta Overexpression in Colonic Tumorgenesis

Colon cancers are the second most common cause of cancer death in the United States. Despite progress that has been made, the death rates from colorectal cancers remain around 50%, and advanced colorectal cancers are generally incurable, with an average survival rate of approximately two years even with the best currently available treatment. Clearly, better interventions for the prevention and treatment of colorectal cancers are needed. Increased production of the protein peroxisome proliferator-activated receptor delta (PPAR-d) is associated with colon cancer development; however, it is yet to be determined if increased production of this protein in cancer cells promotes colon cancer development. The proposed project aims to address this question by simulating what happens in human colon cancer in mice that are genetically engineered to overproduce the protein in colon cells. This improved understanding is expected to determine if new drugs can be developed to target PPAR-d to prevent and treat colon cancer.

Novel Use of the Niclosamide: Targeting mTOR Signaling in Peutz-Jeghers Syndrome

Peutz–Jeghers syndrome (PJS) is a genetic disorder characterized by benign polyps called hamartomas which occur mainly in the stomach and small and large intestines. Patients with PJS are at higher risk for developing various types of cancer. To date, therapy for PJS has been limited to surgical removal of clinically significant polyps. Over-activation of mTOR signaling, a pathway which promotes cell growth and proliferation, has been associated with PJS suggesting that an  mTOR inhibitory drug may be useful for PJS treatment. In this proposed project, we will use niclosamide, a novel mTOR inhibitor drug, to determine whether inhibition of mTOR signaling suppresses polyp formation in the PJS mouse model. Considering that the mTOR pathway is aberrantly activated in most common cancers in addition to PJS, the resulting findings could impact not only PJS prevention and treatment but also other cancers with dysregulated mTOR signaling. 

Preclinical Chemoprevention of Esophageal Adenocarcinoma

The incidence of esophageal cancer, a deadly disease with a poor prognosis, has been increasing in the U.S. The actual origin of esophageal cancer remains unclear, but we do know esophageal cancer is more likely to occur in individuals who have frequent gastroesophageal reflux carrying acid, bile and protease, resulting in the formation of Barrett's esophagus. The latter is considered to be a premalignant condition that may lead to the advancement of esophageal cancer. Tobacco smoke can also enhance the effects of bile acid, which may in and of itself be a risk factor for esophageal cancer. These risk factors contribute to development of esophageal cancer by causing multiple genetic changes. In this study, in animal models, we will investigate how these risk factors contribute to esophageal cancer by blocking the activity altered genes to determine if these prevents or delays development of esophageal cancer and blocks the growth of esophageal cancer cells.

Predicting the Link of Developing Lung Cancer: A Multigenic Statistical Approach to MicroRNA

Lung cancer is the leading cause for cancer-related death in the U.S., with almost 90% of lung cancers attributed to cigarette smoking. There is substantial evidence that the process of developing lung cancer is driven by the interaction between exposure to external cancer-causing substances and inherent genetic traits. This study will identify novel genetic variants in miRNA related genes, a type of RNA that plays important regulatory roles in many biological processes and diseases, and are associated with the development of lung cancer. We will explore gene-gene interactions and gene-environment interactions, use analytical and statistical techniques to then develop and validate models, which will help to identify individuals at highest risk for lung cancer who then may be prospects for targeted prevention interventions. The results of this study may shed significant light into a cause of lung cancer and lead to new techniques to identify those at high-risk for this disease.