Research Newsletter
American Cancer Society Pilot Project Awardees Announced
Four Indiana University investigators received American Cancer Society pilot project grants of $25,000. The awards assist young investigators in the ranks of assistant professor, research assistant professor and assistant scientist starting their independent research projects. They also foster cancer research at the campuses of Indiana University School of Medicine in Indianapolis and at the regional centers of the Medical School.
Waleed Abdel-Aziz, Ph.D., research assistant professor of medicine and cancer center member, received a grant for the “Identification of Malignancy-Dependent Isoforms of Poly(ADP-Ribose) Polymerase-1 (PARP-1).” The development of cancer involves alteration and malfunctions of several key cellular genes in the processes of DNA replication, repair and genome integrity. As has been demonstrated in breast cancer, structural alterations in proteins involved in DNA replication and repair result in low replication fidelity, one of the hallmarks of cancer. This led to Abdel-Aziz’ hypothesis that there might be a direct link between specific alterations of the components of DNA synthetic apparatus and the lower DNA replication fidelity observed in malignant breast cells. Poly(ADP-ribose) polymerase-1 (PARP-1) is one of the proteins that play an important role in DNA replication and repair processes. Abel-Aziz and colleagues have recently identified altered isoforms of PARP-1 which are unique to breast cancer cells - the first evidence that shows altered forms of this protein in breast cancer. In order to test whether these altered PARP-1 isoforms could be utilized for early detection of cancer, Abdel-Aziz and colleagues will validate and define the structure and function of these isoforms in different stages during breast cancer development and progression. An experimental mammary tumor model induced in female rats, as well as in a cell line-based cancer progression model, will be used. The results obtained from this project are critical to help understand the molecular basis by which breast cancer cell DNA replication apparatus becomes error-prone, a key process in breast cancer development and progression. It is anticipated that differences in the structure and function of PARP-1 in malignant and non-malignant breast cells could be utilized not only as an early signature for malignancy but as a novel therapeutic target as well.
Zane Hammoud, M.D., assistant professor of surgery and affiliate member of the cancer center, received funding to study the “Molecular Mechanisms Underlying Gender Differences in Lung Adenocarcinoma.” The project attempts to obtain a better understanding of the differences seen in lung cancer between men and women. Clinically, significant differences are observed in the types and behavior of lung cancer in men and women. Hammoud and colleagues will attempt to explain such differences by looking at the genetic and/or hormonal differences that may play a role in the development of lung cancer.
Jeremy Sanford, Ph.D., assistant professor of biochemistry and molecular biology, received a grant to study “Post-transcriptional control of gene expression by KOC in pancreatic cancer.” Pancreatic cancer is a highly lethal disease marked by pain, anorexia, sleep problems and weight loss. Pancreatic cancer is the fourth most common cause of cancer-related deaths worldwide, with an estimated incidence of nine patients in 100,000 individuals. Despite the high prevalence of this devastating disease, relatively little is known concerning the molecular changes differentiating normal tissue from pancreatic cancers. Conventional treatment approaches such as chemotherapy, radiation surgery or combinations of these methods have had little impact on the course of this disease in patients. It is clear that a better understanding of the etiology and biology of pancreatic cancer is urgently needed to effectively diagnose, prevent and treat this malignancy. This work will investigate a novel aspect of pancreatic cancer. In some cancers such as pancreatic, the cancer cell can hijack genes normally only switched-on during fetal development and are virtually undetectable in adult tissues. One such gene produces a protein called KOC. The KOC protein is thought to switch other genes on or off. The goal of this project is to identify the genes that are controlled by KOC in cancer cells. The study will investigate the targets and functions of KOC, a virtually unexplored area of pancreatic cancer biology. The work will have implications for other cancer systems as well as developmental biology and mechanisms of gene expression.
Clark Wells, Ph.D., assistant professor of biochemistry, received a grant to investigate the “Role of the Cellular Polarity Protein Amot in Migration and Invasion of Epithelial Tumors.” When a cancer grows as a mass of cells that tightly bind to each other, the chances for a cure are often quite good. When the cancer cells gain the ability to leave the tumor and move to other parts of the body to establish new tumors or metastasize, the cancer often becomes life-threatening. This study aims to show that the ability of cancer cells to leave the tumor can be initiated when the tumor causes a factor called Amot to be more prevalent in the cell. By showing that Amot is necessary for cells in certain tumors to migrate to other parts of the body, it may be possible in the future to find a way to block Amot and thereby prevent metastasis. This would make those types of cancers much less deadly.
