Center Funds Important New Pilot Studies

The Northwestern Physical Sciences-Oncology Center (NU-PSOC), under the leadership of Prof. Jonathan Widom, recently awarded a total of nearly$300,000 to NU investigators for one-year pilot studies related to the Center’s theme of “Coding, Decoding, Transfer and Translation of Information in Cancer.”  The Center awarded an additional $100,000 to support the incorporation of needed expertise into existing Center research projects.

The NU PS-OC is one of 12 such Centers established by the National Cancer Institute in 2009 to apply concepts and methodologies from the physical sciences and engineering to the study of cancer biology. Under the terms of its $12.5 million award from the National Cancer Institute, the NU PS-OC must devote some of these funds each year to support  pilot projects that complement and expand the Center’s five main projects.  In its second round of underwriting these studies, the NU-PSOC selected three promising pilot projects for support.  Marcus Peter, Dept. of Medicine/Hematology-Oncology, received $100,000 for his project “Development of Novel Tools to Detect and Inhibit MicroRNAs.  MicroRNAs, a recently discovered species of non-coding RNA, play an important role in the mis-regulation of gene expression in cancer cells, and agents that can block microRNA action may have therapeutic benefit in cancer. However, there are many closely related microRNAs whose actions and targets are very hard to distinguish, complicating the development of effective blocking agents. Dr. Peter proposes a novel approach using antibody fragments that may allow individual microRNAs in a family to be detected and inhibited, with the ultimate goal of developing these antibody fragments as cancer therapeutics.

A second $87,500 award was given to Dr. Carol LaBonne, Dept. of Molecular Bioscience, for her project “Epigenetic Regulation of the Stem Cell State, and Relation to EMT and Invasiveness ($87,500).  In these studies, Dr. LaBonne will use a model organism, the zebra fish, to examine the epigenetic marks that accompany and may contribute to a critical embryological transition, the establishment of the neural crest stem cell population.  Neural crest cells exhibit migratory and invasive behaviors, which are required for their normal function during embryogenesis.  Importantly, metastatic tumors cells reacquire these motile and invasive behaviors that are normally confined to embryological development, with deadly consequences for cancer patients.  Epigenetic marks are modifications to either the DNA or the protein components of chromatin.  These modifications are heritable and can alter gene expression, but they do not involve changes to DNA sequence and are therefore not classified as mutations.  In this project, Dr. LaBonne will examine specific modifications to histones, proteins that form a core around which DNA is wrapped in the nucleus.

A third pilot project award of $87,500 was made to Dr. Neil Kelleher, Dept. of Molecular Biosciences,  for his project “Combining CHIP-Seq and Mass Spectrometry to Measure the Effects of Histone Methylation on Nucleosome Positioning and Aberrant Methyltransferases in Lymphoma.”    Dr. Kelleher is a recognized expert in the technique of mass spectrometry, a method to identify proteins based on precise measurements of the masses of charged peptides that are generated by ionizing the proteins.   This technique can be used to measure histone modifications.  In this pilot project, Dr. Kelleher will collaborate with the laboratory of Dr. Widom, which has demonstrated that the position of nucleosomes in the yeast genome is largely determined by DNA sequence.  Dr. Kelleher will now ask whether epigenetic changes, and in particular, the presence or absence of a particular histone modification, also affects nucleosome positioning.

These investigators will join the Center’s 27 faculty members in participating in quarterly Center research meetings, symposia, workshops, and annual NCI site visits.  Support for the NU-PSOC Pilot Project program comes from NCI grant 5U54CA143869-02, cost shared support from Northwestern University, and a generous contribution from the Robert H. Lurie Comprehensive Cancer Center.

In addition to funding pilot projects, the NU-PSOC also supports activities and small projects  designed to foster collaborations between Center investigators and investigators outside of the PS-OC network.  These smaller awards (ranging from $10,000 to $25,000) allow Center researchers to send students and postdoctoral researchers to labs outside of the PSOC network for additional training and to sponsor visits from researchers who will enable them to expand their current projects.  Outreach project funding has been awarded to:  Elizabeth Eklund, “Role of Transcriptional Accessibility of Hox Loci in Poor Prognosis AML” ($25,000); Alexandre DeLuna, (Center Collaborator: Adilson Motter)  “Understanding how Genes, the Environment, and their Interactions Determine Synthetic Rescue” ($25,000); John Marko, (Collaborator: Kazuhiro Maeshima),  “Technique Development for Isolation and Visualization of Mitotic Chromosomes” ($10,000); Milan Mrksich, (Center Collaborator: Jonathan Licht), “The Chemical Biology of MMSET” ($12,500); and Igal Szleifer, (Center Collaborator: Vadim Backman)  “Microscopic Modeling of Nanoarchitecture Changes in Cancer Cells” ($25,000).