May 2013 Damon Runyon Fellows:
Shreeram Akilesh, MD, PhD, with his sponsor John A. Stamatoyannopoulos, MD, at the University of Washington, Seattle, Washington, focuses on regions of the genome previously thought to be "junk DNA." Recent studies demonstrate that they in fact contain motifs that serve a vital function in gene regulation. Using next-generation sequencing strategies and advanced bioinformatics analyses, he will study the reprogramming of regulatory DNA regions as normal kidney tissues transform into cancers. This research will provide insights into the genomic regulation of kidney cancer that could be used to develop more effective treatments.
Christine Iok In Chio, PhD, with her sponsor David A. Tuveson, MD, PhD, at Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, works on pancreatic cancer, which is a particularly devastating and difficult-to-treat disease because of its ability to grow in conditions of high oxidative stress—conditions in which normal cells would not survive. She is evaluating the biological role of oxidative stress in pancreatic cancer development and progression, using both mouse models of pancreatic cancer as well as human tumor samples.
Tracy T. Chow, PhD, with her sponsor Elizabeth H. Blackburn, PhD, at the University of California, San Francisco, California, studies the molecular basis of how cancer cells maintain the ability to divide indefinitely. In most human cancers, an enzyme named telomerase is crucial in maintaining chromosomal ends (or telomeres) to achieve immortality. She is exploring a novel mechanism for telomere maintenance, which could advance the development of improved therapeutics for glioblastoma and other cancers.
Michael A. Cianfrocco, PhD [HHMI Fellow] with his sponsors Andres Leschziner, PhD, and Samara L. Reck-Peterson, PhD, at Harvard University, Cambridge, Massachusetts, studies proteins called dynactin and dynein that function to transport organelles within the cell, a process that is particularly important during cell division. He aims to elucidate the structural basis for dynactin's ability to regulate dynein activity. Since many viruses, including cancer-causing oncoviruses, require dynein to be transported from the cell membrane to the nucleus for genome replication, understanding the molecular details of dynein-dynactin function may provide novel targets for cancer therapies.
Justin M. Crest, PhD, with his sponsor David Bilder, PhD, at the University of California, Berkeley, California, is studying the mechanical forces between cells and their underlying substrate, or extracellular matrix (ECM). The physical properties of cells and the ECM shape tissues during development and are critical for malignant tumor progression and metastasis. His research will determine which molecules generate and balance the mechanical forces involved in migration and tissue formation and thus identify novel mechanisms of malignancy.
Mary Williard Elting, PhD, with her sponsor Sophie Dumont, PhD, at the University of California, San Francisco, California, studies the mechanics of cell division, with the goal of understanding how cells accurately transmit one copy of their genetic information into each of two daughter cells. Mistakes in this process are implicated in cancer, as well as birth defects and miscarriage. She will mechanically disrupt dividing cells and then detect how these perturbations affect the forces generated during division.
Wenwen Fang, PhD [HHMI Fellow] with her sponsor David P. Bartel, PhD, at theWhitehead Institute for Biomedical Research, Cambridge, Massachusetts, aims to understand the mechanism and regulation of microRNA biogenesis. MicroRNAs function to regulate gene expression and their disruption contributes to the initiation and progression of cancer. She will combine high-throughput sequencing techniques and biochemistry to examine the recognition and processing of microRNA precursors, which may ultimately contribute to more effective cancer diagnosis and therapy.
Jessica P. Lao, PhD, with her sponsor David P. Toczyski, PhD, at the University of California, San Francisco, California, focuses on genome instability and altered metabolism, which are common characteristics of cancer. The "DNA damage checkpoint" detects and repairs DNA damage to maintain genomic integrity and has also been implicated in regulating metabolism through an unknown mechanism. Identifying metabolic targets of the DNA damage checkpoint will advance our knowledge of the underlying signaling pathway and provide additional targets for cancer therapy.
Steven Lin, PhD [HHMI Fellow] with his sponsor Jennifer A. Doudna, PhD, at the University of California, Berkeley, California, investigates the molecular mechanism by which the bacterial enzyme Cas9 targets and cleaves double-stranded DNA. His goal is to provide a detailed understanding of Cas9 mechanism and structure, ultimately aiming to develop Cas9 into a versatile genome engineering tool for further studies of cancer-associated genes.
Xiaoxiao Shawn Liu, PhD, with his sponsor Philip A. Beachy, PhD, at Stanford University, Stanford, California, focuses on the Hedgehog signaling pathway, which plays a central role in embryonic development and tissue regeneration. Dysfunction of this pathway is associated with numerous cancers. He aims to understand how the exterior signal of Hedgehog is transduced across the cell membrane by a membrane protein called Smoothened. A deeper understanding of Hedgehog signal transduction will provide a basis for novel therapies to prevent and inhibit cancers.
Andrew R. Nager, PhD [Fayez Sarofim Fellow] with his sponsor Maxence V. Nachury, PhD, at the Stanford University School of Medicine, Stanford, California, is studying the primary cilium, an organelle that cells use to sense the environment and communicate with other cells. To do so, the primary cilium selectively exchanges signaling molecules with the cell body. He is using cell biology, biochemistry, and biophysics to understand the gate between the primary cilium and the cell body. Because dysfunctions of the primary cilium promote cancer and cause developmental disease, this research is an important new avenue of exploration.
Beverly J. Piggott, PhD, with her sponsor Yuh Nung-Jan, PhD, at the University of California, San Francisco, California, is exploring the role of ion channels in brain cancer. Ion channels function as a "gate" to regulate the movement of ions (such as sodium and potassium) into and out of the cell. They are essential for proper cell growth and signaling in normal cells, and misregulation or mutations in ion channels have been linked to cancer cell proliferation and metastasis. Her goal is to obtain mechanistic insight into the function of ion channels in brain tumors, which may provide new targets for diagnosis and therapeutic intervention.
Alex Pollen, PhD, with his sponsor Arnold R. Kriegstein, MD, PhD, at the University of California, San Francisco, California, is using comparative genomics, single cell gene expression, and stem cell biology approaches to study genes uniquely expressed in human neural stem cells. Because the development of the human brain involves many of the same processes – increased proliferation, migration, and angiogenesis – that become dysregulated in brain tumors, these genes with specific neural stem cell expression may serve as therapeutic targets and diagnostic markers of brain tumor stem cells that initiate glioblastoma and other cancers.
Jens C. Schmidt, PhD [Merck Fellow] with his sponsor Thomas R. Cech, PhD, at the University of Colorado, Boulder, Colorado, focuses on understanding how the enzyme telomerase maintains the length of the ends of human chromosomes. This process is crucial to prevent chromosome fusion events, a strong driving force of cancer. In addition, 90% of all cancers require telomerase activity for survival, making it a potential target for cancer therapy. He will use a combination of biophysical, biochemical and cell biological approaches to elucidate how telomerase is recruited to chromosome ends and to identify potential inhibitors of this process.
Eric L. Van Nostrand, PhD [Merck Fellow] with his sponsor Eugene Yeo, PhD, at the University of California, San Diego, California, aims to understand how alterations in RNA processing can lead to cancer development and progression. He will identify RNA processing factors that drive medulloblastoma brain tumor growth and proliferation, and use genomics techniques to profile their regulatory targets. This network will both serve as a tool for understanding basic mechanisms of neuronal and medulloblastoma development and progression, and a means to identify critical modulators of tumor development that can serve as targets for future therapeutics.
Jakob von Moltke, PhD [HHMI Fellow] with his sponsor Richard Locksley, MD, at the University of California, San Francisco, California, studies how the immune system detects bacteria and parasitic worms. Emerging evidence suggests that these same immune cells also respond to tissue damage in the absence of infection, suggesting an evolutionary role in wound healing. He is examining how these cells are regulated during wound healing and how their activity contributes to tissue regeneration and repair. Since tumors regularly hijack the body's natural wound healing processes, his findings should provide insight into tumorigenesis and could suggest novel therapeutic strategies.
Victoria E.H. Wang, MD, PhD, with her sponsor Frank McCormick, PhD, at the University of California, San Francisco, California, seeks to understand the mechanisms by which tumor cells become resistant to drug therapy and spread to distant organs. She is utilizing functional genomics tools to identify novel pathways modulating these processes in the hope of developing new therapies to augment treatment response in cancer patients.
Provided by Damon Runyon Cancer Research Foundation
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