Five Consortium teams win pilot grants

Five collaborative teams within the Fred Hutchinson/University of Washington Cancer Consortium have received Cancer Center Support Grant (CCSG) Pilot Awards for 2012. The pilot grants are presented every year to fund new Consortium research directions and collaborations.

This year, the Consortium received an overwhelming response to the request for applications. In a very competitive process and after careful consideration, the pilot award committee chose five applications from among the 77 submitted.

In an era of tight National Institutes of Health funding, CCSG pilot grants are a particularly important mechanism supporting investigators as they gather critical data to substantiate a future NIH grant. Each pilot grant is for $100,000 direct costs, plus facilities and administrative costs.

The 2012 grants will support a diverse range of inquiries. They are:

• Drs. Antonio Bedalov and Joachim Deeg, Clinical Research; and Dr. Joshua Ackey, UW Genome Sciences
  Analysis of Monoallelic Expression in Myelodysplastic Syndrome by Next Generation Sequencing
  In human cells, genes are present in two copies and it is generally assumed that both copies of each gene are expressed at the same level, with some notable exceptions. The Bedalov Lab, in collaboration with the Deeg and Ackey groups, is using next generation sequencing technology to study gene expression in patients with myelodysplastic syndrome (MDS), a chronic condition that greatly increases the risk of developing acute myelogenous leukemia. Initial findings indicate that the MDS cells show a striking increase in number of genes expressing only one copy, or monoallelic expression. A comprehensive understanding of this phenomenon may improve prediction of disease progression in MDS patients.
  
• Dr. Daniel Chiu, UW Chemistry; Dr. Keith Eaton, UW Oncology; and Dr. Hubert Vesselle, UW Radiology
  Isolation and Profiling of Circulating Tumor Cells from Lung Cancer Patients with eDAR
  This collaboration between a chemist and two clinical researchers seeks to improve the care and survival of non-small cell lung cancer patients by identifying tumor characteristics that help predict tumor behavior. Tumor cells that have entered the circulation are easily accessed through a simple blood draw and may offer a unique window into the biology of a tumor. However, one of the main challenges of working with these cells is their low numbers in the blood. The Chiu Lab has developed technology that can efficiently and economically sort live circulating tumor cells from the blood. Using this technology, this interdisciplinary group will compare circulating tumor cells to those of the primary tumor and to the complete tumor burden and stage, the tumor response to therapy, and overall patient outcome.
  
• Dr. Phil Greenberg, Clinical Research and UW Immunology, and Dr. Sunil Hingorani, Clinical Research
  T-Cell Therapy of Pancreatic Ductal Adenocarcinoma
  This pilot study seeks to establish an immunotherapy strategy, as pioneered in the Greenberg Lab, in the mouse model of pancreatic ductal adenocarcinoma developed by the Hingorani Lab. Together these groups will test whether T-cell antigens that are expressed in both mouse and human pancreatic cancer in combination with agents being developed in the Hingorani Lab to increase chemical and T-cell infiltration of the tumor can be developed into a safe and effective strategy for immunotherapy of advanced pancreatic ductal adenocarcinoma.
  
• Drs. Toshi Tsukiyama and Linda Breeden, Basic Sciences
  Epigenetic Regulation of Quiescent Cell State
  Most eukaryotic cells, from yeast to humans, spend the bulk of time in a quiescent or nondividing state, and unscheduled exit or failure to enter the quiescent state is often associated with human cancer. The Breeden Lab recently discovered that highly conserved regulators of DNA structure, called chromatin, are necessary for the entry into quiescent state. In close collaboration with the Breeden Lab, the Tsukiyama Lab—experts in the analysis of chromatin—will analyze changes to the DNA that occur as cells enter the quiescent state. These changes in DNA structure are likely to modulate gene expression, in turn revealing new mechanisms that may explain the loss of quiescence and uncontrolled cell growth that occurs in many cancers.
  
• Dr. Emily White, UW Epidemiology; and Dr. Johanna Lampe, Public Health Sciences
  A Pilot Trial of Glucosamine and Chondroitin: Effect on a Serum Biomarker of Inflammation
  Chronic inflammation is associated with the development of many cancers. Glucosamine and chondroitin, commonly used dietary supplements, have anti-inflammatory properties, including inhibition of NF-kB, a transcription factor involved in inflammation. Pilot funding will support a randomized, crossover, placebo-controlled trial of G&C supplementation to assess its effect on a biomarker of inflammation and, overall, the chemopreventive potential of G&C.
  

Progress for previous pilot grant winners

Previous pilot grantees have used their CCSG funding to begin new collaborations and support a new area of research in their labs, including:

• Dr. Roland Walter, Clinical Research Division, whose work on the clinical significance of adhesion molecules and extracellular matrix proteins in Pediatric Acute Myeloid Leukemia has developed into a recent R21 grant.
• Dr. Susan Parkhurst, Basic Sciences Division, whose study of nuclear roles for WASH, a new Wiskott-Aldrich Syndrome protein subfamily discovered in her lab, has developed into an R01 exploring the both the nuclear and cytoplasmic role of this important family of regulators of cell shape and movement.
• Dr. Tobias Hohl, Vaccine and Infectious Disease Division, who developed and validated a method to visualize the process of fungal spore killing in the lung and used this method to explore the innate immune response to the pathogen, Aspergillus fumigatus, findings that supported a successful R01 submission.

The next CCSG pilot competition will take place in early 2013. For more information, contact Dr. Marion Dorer, Consortium administrator, at mdorer@fhcrc.org or (206) 667-3001.