Damon Runyon Cancer Research Foundation names 18 new Fellows

Grants totaling over $3.1 million give early career investigators independence to pursue novel ideas

The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting innovative early career researchers, named 18 new Damon Runyon Fellows at its fall Fellowship Award Committee review. The recipients of this prestigious, three-year award are outstanding postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators across the country. The Fellowship encourages the nation's most promising young scientists to pursue careers in cancer research by providing them with independent funding ($156,000 each) to work on innovative projects.

The Committee also named three new recipients of the Dale F. Frey Award for Breakthrough Scientists. This award provides additional funding to scientists completing a prestigious Damon Runyon Fellowship Award who have greatly exceeded the Foundation's highest expectations and are most likely to make paradigm-shifting breakthroughs that transform the way we prevent, diagnose and treat cancer. Each awardee will receive $100,000 to be used toward their research.

Sean C. Bendall, PhD (Damon Runyon Fellow '09-'12), Stanford University, Stanford, California

Dr. Bendall is using novel single-cell analysis techniques to investigate how normal regulatory cell signaling networks are rewired, allowing cancer to grow unchecked. He has applied this technology to examine healthy human blood cells, measuring multiple parameters simultaneously in single cells. Collectively, such single-cell analyses provide an unprecedented opportunity to identify novel regulators (such as drugs, genes, and protein modifications) of cell development and identity, as well as provide insight into how these regulators interact with genes and mutations that promote cancer cell transformation. His goal is to use these studies to contribute to the development of more effective diagnostics and treatments to improve clinical outcomes.

Robert K. Bradley, PhD (Damon Runyon Fellow '09-'11), Fred Hutchinson Cancer Research Center, Seattle, Washington

Alternative splicing, the process by which a single gene can give rise to multiple, distinct protein isoforms, is broadly dysregulated in many tumors. Recent research demonstrates that erroneous splicing can play important roles in tumor formation and growth, making it crucial that we understand the regulatory processes that give rise to aberrant splicing in cancers. In collaboration with clinicians, Dr. Bradley seeks to identify splicing events with important roles in tumor formation and maintenance. By combining computational and experimental techniques to understand the regulatory mechanisms underlying aberrant splicing, he aims to gain insight into fundamental tumor biology, potentially pointing the way to future therapeutics.

Dr. Bradley is now Assistant Member at the Fred Hutchinson Cancer Research Center, Seattle, Washington.

Jason M. Crawford, PhD (Damon Runyon Fellow '09-'11), Harvard Medical School, Boston, Massachusetts

Small molecules produced by bacteria and fungi have provided many of our most successful anticancer drugs. These microbial products have also served as excellent probes for identifying new drug targets in a variety of cancers. Dr. Crawford will exploit the natural interactions between bacteria and animals to increase the production and identification of new products with anticancer activities. By understanding how these products are produced in the microbe, the pathways can then be engineered to produce a variety of pharmacologically-relevant molecules.

Dr. Crawford will also explore the chemical interactions that occur between humans and the bacteria on our skin and in our gut. Many of these bacteria help to digest food, produce vitamins, ward off pathogens, and train the immune system. By parsing apart the chemical interactions at the microbe-human interface, he will better understand how to minimize microbes capable of causing cancer while maximizing protective ones.

Dr. Crawford will soon be moving to an Assistant Professor faculty position at Yale University, New Haven, Connecticut.

Mary J. Carroll, PhD, with her sponsor Stephen W. Fesik, PhD, at Vanderbilt University Medical Center, Nashville, Tennessee, aims to design small molecule inhibitor drugs with high affinity for the protein Vav1. This protein is an attractive target for treating pancreatic cancer because it is highly expressed in pancreatic adenocarcinomas and activates pro-cancer signaling.

Sidi Chen, PhD, with his sponsor Phillip A. Sharp, PhD, at Massachusetts Institute of Technology, Cambridge, Massachusetts, aims to understand the relationship between small RNAs and cancer. Small RNAs are important regulators of genetic networks inside the cell; perturbation of these networks can lead to malignant cell growth. His goal is to develop anti-cancer drugs and therapies by targeting the process of small RNA production.

Stephanie T. Chen, PhD, with her sponsor David J. Julius, PhD, at University of California, San Francisco, California, is studying somatosensation, the sense of "touch," with a focus on pain sensation. She aims to identify novel proteins that a) drive the development of sensory neurons, and b) confer the ability to detect painful stimuli under normal and pathophysiological conditions, including those leading to cancer-induced pain.

Jason A. Hall, PhD, with his sponsor Dan R. Littman, MD, PhD, at New York University School of Medicine, New York, New York, is investigating the biochemical and metabolic pathways that regulate the activity of the protein ROR gamma t, which has crucial importance in metabolism and immune system homeostasis. It is also linked to the development of chronic inflammation, a known trigger and promoter of certain tumor types. Understanding its regulation will facilitate the development of new therapeutics to manage chronic inflammatory disease and prevent tumorigenesis.

John J. Karijolich, PhD, with his sponsor Michael Hampsey, PhD, at UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey, aims to define mechanisms involved in the regulation of gene expression, using a combination of biochemical and genetic approaches. An understanding of these mechanisms is key to understanding the development of cancer, and may potentially lead to novel cancer therapeutics.

Ralph E. Kleiner, PhD, with his sponsor Tarun M. Kapoor, PhD, at The Rockefeller University, New York, New York, is studying proteins called microtubules, which play a crucial role in the maintenance and proliferation of cancer cells. Microtubule function is regulated, in part, by chemical modifications or "flags" on the microtubule proteins. He aims to combine chemical, biochemical and biophysical approaches to better explain the role of these modifications on cell physiology and drug sensitivity. These studies will enable the identification of novel strategies for improving the efficacy of existing microtubule-targeted cancer drugs.

Ryota Matsuoka, PhD, with his sponsor Didier Y.R. Stainier, PhD, at University of California, San Francisco, California, is investigating how the nervous and vascular systems cooperate to establish precise patterns of networks. Neuronal and vascular networks are fundamental for normal tissue function and homeostasis, and abnormalities in these networks lead to tissue dysfunction and diseases, including cancer.

Robert K. McGinty, MD, PhD, with his sponsor Song Tan, PhD, at Pennsylvania State University, University Park, Pennsylvania, is examining the structure and function of enzymes called methyltransferases. As these enzymes are commonly misregulated in human leukemias, an understanding of their normal function may provide insight into novel platforms for drug development.

Cory Y. McLean, PhD, with his sponsor Joseph F. Costello, PhD, at University of California, San Francisco, California, is interested in understanding how low-grade brain tumors change to become high-grade tumors. He is studying primary and recurrent brain tumors to identify the genetic and epigenetic alterations that differentiate tumors from normal tissue and cause tumor transformation from low- to high-grade. These studies may identify new targets for future drug development or indicate existing treatments that could be used to effectively treat low-grade tumors.

Katarina Moravcevic, PhD, with her sponsor Amita Sehgal, PhD, at University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, is studying sleep deprivation, which leads to an increased risk of several diseases including cancer. Little is currently known about the function of sleep or about the molecular mechanisms that control the need to sleep. To begin to understand why sleep deprivation has such a negative impact on human health, she will address how and why the need to sleep builds up after prolonged wakefulness.

Renee Otten, PhD, with his sponsor Dorothee Kern, PhD, at Brandeis University, Waltham, Massachusetts, is investigating the catalytic mechanism of protein kinases, an important family of proteins that are present in bacteria, plants and humans. These proteins play a central role in signal transduction pathways and orchestrating the cell cycle; aberrant activity, however, has been shown to cause certain human cancers. A firm grasp of their mechanism is thus of great interest because it holds promise for the development of new therapeutics.

Douglas H. Phanstiel, PhD, with his sponsor Michael P. Snyder, PhD, at Stanford University School of Medicine, Stanford, California, is studying transcription factors (TF), proteins that bind to DNA and regulate gene expression. Certain TFs have well-established roles in cancer and other diseases. He is using chromatin immunopreciptation combined with high-throughput sequencing (ChIP-Seq) to map TF-DNA binding sites in a variety of yeast strains. This research is expected to be important for understanding the mechanisms controlling gene expression in humans and their variation across populations, thus providing insights into cancer and other diseases.

Maximilian W. Popp, PhD, with his sponsor Lynne E. Maquat, PhD, at University of Rochester School of Medicine and Dentistry, Rochester, New York, is focusing on the quality control mechanisms that cells utilize at the RNA level to ensure proper gene expression. Cells inspect and destroy aberrant mRNA messages using decay pathways; dysregulation of these RNA decay systems is implicated in various cancers. He will apply a new genetic screening method to identify components of RNA decay pathways and learn more about their role in cancer.

Leah R. Sabin, PhD, with her sponsor Gregory J. Hannon, PhD, at Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, is studying the role of long noncoding RNAs (lncRNAs) in blood cell development. Although the precise function of most lncRNAs remains unclear, certain lncRNAs are involved in regulating gene expression and may therefore be important for proper blood cell maturation. Since several types of cancers arise from blood cell progenitors, understanding how lncRNAs function in these cells may provide novel diagnostic and therapeutic targets.

Peter J. Skene, PhD, with his sponsors Mark T. Groudine, MD, PhD, and Steven Henikoff, PhD, at Fred Hutchinson Cancer Research Center, Seattle, Washington, is studying the mechanisms underlying how cells maintain a specific gene expression profile unique to that cell type. While current technologies allow the reprogramming of differentiated cells into stem cells, the therapeutic use of this technology is limited because not all cellular memory is erased. He aims to improve the reprogramming process by removing proteins responsible for cellular memory. Stem cells have great potential in regenerative medicine, such as in renewing bone marrow following chemotherapy during cancer treatment.

Lora B. Sweeney, PhD, with her sponsors Christopher R. Kintner, PhD, at The Salk Institute for Biological Studies, La Jolla, California, and Thomas M. Jessell, PhD, at Columbia University, New York, New York, is using the frog as a model to study how neurons diversify in the spinal cord as limbs develop and a swimming tadpole becomes a hopping frog. Many different types of nerve cells, each with their own unique characteristics, make up the healthy nervous system. Understanding how a cell's fate is specified will provide the basis for understanding how cancer reprograms a cell.

Yanling Wang, PhD [Robert Black Fellow] with her sponsor Jeffery F. Miller, PhD, at University of California, Los Angeles, California, is studying Bacteroides fragilis, a common human gut bacterium that protects against inflammatory bowel diseases (IBD) in experimental models. This project will explore the mechanisms that contribute to bacterial colonization and long‐term maintenance in the gut. By combining bioinformatics, molecular genetics, protein biochemistry and innovative animal disease models, she hopes to better understand host‐microbe and microbe‐microbe interactions in the complex mammalian gut environment, and to potentially utilize B. fragilis as a preventative and therapeutic against IBD and/or colon cancer.

Rui Yue, PhD, with his sponsor Sean J. Morrison, PhD, at University of Texas Southwestern Medical Center, Dallas, Texas, is investigating the role of Leptin receptor signaling in blood stem cells (hematopoietic stem cells, HSCs). Leptin signals the nutritional status of the body and tightly controls energy metabolism and body weight. Interestingly, bone marrow stromal cells surrounding HSCs express very high levels of Leptin receptor; it is therefore possible that HSCs, which can initiate leukemia in pathological conditions, are regulated by nutritional changes in the microenvironment through Leptin signaling. These studies may enable successful HSC expansion and transplantation after chemotherapy in leukemia patients, and may also help prevent or treat other types of cancer.