2009 Norris Cotton Cancer Center Research Awards

These awards are made from time to time at the discretion of the Cancer Research Committee to fund projects of particular merit, as identified through a peer-review process defined by the Cancer Center Administration.

Project: "Partitioning Chromatin Domains in Breast and Prostate Cancer Cells"

Principal Investigator: Mathieu Lupien, PhD
Cancer Type: Breast
Cancer Center Pilot Project Grant: $30,000

Project Summary: Although cancer is typically thought of a genetic disease, there is increasing evidence that alteration to the chromatin structure of normal cells is involved in oncogenesis. Indeed, chromatin domains typically inaccessible by the transcriptional machinery in normal tissues become accessible in cancer cells and vice versa. Our work proposes to characterize the role of the BORIS protein in cancer cells. This DNA binding protein shares its specificity for chromatin recruitment with the CTCF protein central in chromatin domain partitioning. While BORIS is normally expressed only in testes, it is commonly over-expressed in many different types of cancers. Therefore, it is expected to significantly alter CTCF function and contribute to the altered partitioning of chromatin domains typical of cancer cells. BORIS has previously been shown to play a central role in breast cancer, where it is involved in the expression of the estrogen receptor alpha (ERα), a central regulator of this disease. We intend to reveal its genome-wide mode of action as well as target chromatin regions in breast cancer cells. Considering the restricted normal expression of BORIS in testes, our research is expected to lead to novel therapeutic approaches to breast cancer with minimal side effects. In addition, we anticipate that the discoveries made with regards to breast cancer will have applications to other types of cancers, namely lung and ovarian cancer, where BORIS is commonly over-expressed.

Project: "Novel Biomarkers and Potential Therapeutic Targets Using and RNA-Based Platform to Profile the Proteome in a Pancreatic Cancer Cell Line"

Principal Investigator: Craig Tomlinson, PhD
Cancer Type: Pancreas
Cancer Center Pilot Project Grant: $30,000

Project Summary: Pancreatic cancer is the fourth leading cause of cancer death in the United States because most patients are diagnosed too late in the course of their illness to receive an effective treatment. Thus, there is an extremely urgent need to develop powerful new ways to diagnose pancreatic cancer at earlier stages. We are proposing to test the hypothesis that a group of molecules not normally examined in pancreatic cancer can provide a window for detecting pancreatic cancer at earlier stages. We propose to use a relatively new technology in the biological and medical fields called microarray or DNA chip technology. Microarray technology provides a way for the researcher to view all of the mRNAs in a cell. mRNAs provide the templates to make all the proteins of the cell. We propose to examine a special group of mRNAs called polysomes, which is a subgroup of mRNAs that are in the active process of being made into proteins. Proteins, in turn, carry out most of the functions of the cell such as cell division and cell motility and provide many of the structures in the body such as hair and collagen. Using this approach, we intend to identify the genes that encode the mRNAs in polysomes using a human pancreatic cell line that exhibits many of the features found in actual human pancreatic cancers. We describe work in which polysomes are a very accurate way to determine what proteins will be expressed in cells. Thus, our proposed approach may provide a new means to generate novel identifiers of the early stages of pancreatic cancer. The planned work is highly significant because in addition to identifying new genes indicative of the early stages of pancreatic cancer, the proposed methods are rapid, efficient, and cost-effective. Ultimately, the generated data will allow for new ways to analyze human pancreatic tumors and the potential to find new drug targets.

Project: "Orthine Decarboxylase Polymorphisms and Risk of Colorectal Adenoma"

Principal Investigator: Elizabeth Barry, PhD
Cancer Type: Colon
Cancer Center Pilot Project Grant: $30,000

Project Summary: Colorectal cancer is the second leading cause of cancer death in the United States. The research proposed will investigate whether genetic variation in an important regulatory enzyme, call ornithine decarboxylase, alters the risk of developing colorectal adenomas, which are cancer precursors, and whether this genetic variation modifies the protective effect of aspirin in reducing the occurrence of colorectal adenomas. Thus, this research may identify genetic risk factors for colorectal cancer as well as genetic factors influencing which individuals are most likely to benefit from drugs that may be used to prevent colorectal cancer.