University Cancer Research Fund 2009 Innovation Awards Announced

CHAPEL HILL, N.C. - The University Cancer Research Fund Innovation Awards are designed to foster new research, with a preference given to multi-component scientific research in strategic areas within the UCRF’s mission of discovery, innovation, and delivery.

The innovation awards are part of UCRF’s investment in leading-edge researchers and innovative research ideas, which build research capacity, add technology and competitively stimulating innovative research ideas.

These competitive awards are reviewed by a panel of 28 scientists, physicians and researchers.  In this funding cycle, the committee reviewed 48 applications and identified seven awards totaling approximately $1.4M over two years.

The following projects received innovation awards:

Victoria L. Bautch, PhD

Biology / Program in Molecular Biology and Biotechnology
Mis-Regulation of Endothelial Cell Centrosome Numbers in Tumor Vessels

Tumors grow and invade other tissues because they do not respond to normal signals regulating these processes. One of the reasons that tumor cells are unresponsive is because they are genetically unstable – they often have too many or too few chromosomes. Tumors also need blood vessels to feed their growth and provide conduits for cancer cells to spread. These blood vessels have been targeted for cancer therapy because they were thought to be genetically stable. However, we now know that tumor blood vessel cells are not genetically stable, and we propose to understand the causes and consequences of this instability with the ultimate goal of “normalizing” tumor vessels to reduce tumor growth and metastasis. Ultimately, this study might help make therapies targeted at these blood vessels more effective at the cellular and molecular level.


Keith Burridge, PhD

Cell and Developmental Biology
From ECM Rigidity to Activation of RhoA

The physical properties of the surface on which cells are growing affects many of their characteristics, including their shape, their tendency to migrate and whether they grow. Cells on more rigid substrates (or surfaces) typically show enhanced growth. Notably, many tumors become more rigid as they increase in size. Previous work has shown that cells on rigid substrata have enhanced activity of the regulatory protein RhoA, which is known to affect cell migration and cell growth. How cells are able to “sense” the stiffness/elasticity of the surface with which they are in contact has not been determined. This grant brings together a cell biologist, Keith Burridge, and a Physicist, Richard Superfine, to investigate the signaling pathways that lead to RhoA activation in response to growing cells on rigid substrata. In addition, they will investigate the cellular processes controlled by the RhoA pathway in response to stiffness of the substratum. The work should increase our understanding of how changes in the physical properties of tumors, such as their increasing stiffness over time, affect the growth and behavior of the tumor cells. This knowledge may reveal new targets for cancer therapy.


Michael Crimmins, PhD

Chemistry

Synthesis and Mechanism of Action of Irciniastatin A

Some of the most important recent advances in treating cancer have come from naturally-occurring complex molecules, with taxol being one of the best-known examples. In 2004, a highly potent agent, known as irciniastatin A, was isolated from two deep-water marine sponges that seems to selectively kill cancer cells. Unfortunately, the substance was obtained in extremely small quantities and concerns about environmental impact and other issues have hindered large-scale collection of the organisms. Therefore, an efficient way to make the molecule in the laboratory is required in order to further test the substance as a cancer therapy. Dr. Crimmins has developed a first-generation synthesis of irciniastatin A in the laboratory and, in collaboration with Dr. Channing Der, has evaluated the material’s ability to kill melanoma cells. Early data indicates that the substance is a highly potent, selective anti-tumor agent. The two will collaborate with Dr. Klaus Hahn to develop probes and carry out studies to determine how the agent works and generate data that might lead to the development of a unique cancer therapy.


Christopher Sims, PhD
Chemistry

Enabling Lipid Signaling Assays for Clinical Oncology

The study of genes and proteins holds great promise for cancer patient care; however, new approaches are needed to measure the biochemistry of proteins in individual patients. This project will support a collaborative research effort between the Sims and Zhang laboratories to develop new chemical compounds that will be used to make measurements of protein biochemistry in cancer cells. The research will study the feasibility of creating these compounds for a family of proteins that are involved with lipids. Recently, these lipids have been recognized as important in the control of the abnormal cell growth and survival seen in cancer. The researchers will study a particular protein that controls lipid metabolism and that is a target of drugs currently under development. This work will serve as the proof-of-principle to achieve measurements in biopsy or blood samples from a patient. Such studies will provide information on which to base decisions for drug treatment, thus providing a powerful tool for personalizing therapies for each individual patient.


Oliver Smithies, PhD

Pathology and Laboratory Medicine
High Efficiency, Multiplex Gene Targeting in the Tumor Suppressor Gene, p53

The p53 tumor suppressor gene is mutated in approximately half of human cancers, yet few model systems have been established to study the mutations in the laboratory. These cell and animal models are crucial to developing a thorough understanding of human cancers and testing new therapies. We will combine two relatively new technologies to rapidly create a spectrum of known p53 mutations in cell lines for experimental studies. Results of these studies will lead to a more thorough understanding of how p53 mutations lead to tumor formation and have the potential to revolutionize the methods used to create new cell and animal models to study cancer.


Jenny Ting, PhD

Microbiology and Immunology
The Inflammasome and Cancer Vaccines

Inflammation is widely recognized as playing a role in cancer, although there is debate among scientists as to whether inflammation impedes or enhances the growth of tumors. Depending on the tumor, inflammation can activate or suppress the immune response. Improved understanding of these mechanisms is essential to harness anti-tumor immunity and overcome immune suppression caused by tumor cells – both mechanisms need to be understood to create a successful cancer vaccines. This study will pursue our finding that inflammation affects the efficacy of cancer vaccine. Understanding the role of specific inflammatory components in cancer vaccine will allow us to design rational strategies for the containment of cancer.


Melissa Troester, PhD, MPH

Epidemiology
Genomic Profiles of Field Cancerization in Breast

Tissue adjacent to breast cancer often looks normal under the microscope, but has genetic and/or genomic differences from true normal tissue of non-diseased individuals. These genetic changes may be associated with survival outcomes and/or breast cancer subtype. This project will characterize genomic variation in the normal tissue of breast cancer patients using samples and data from two studies: The National Cancer Institute's Polish Women's Breast Cancer Study, and an observational study of normal breast tissue conducted at UNC Lineberger Comprehensive Cancer Center. The results of this study will advance our biologic understanding of normal tissue genomics associated with cancer and the relevance of these changes for breast cancer survival.