New Discoveries and Honors
Read about the latest discoveries by Damon Runyon scientists and honors received by scientists in the Damon Runyon scientific community.
David M. Livingston, MD (Damon Runyon Board Member), of Dana-Farber Cancer Institute, Boston, has been named the 20th recipient of the Pezcoller Foundation-AACR International Award for Cancer Research. Dr. Livingston is honored for his fundamental contributions to the field of basic cancer research. His work has been pivotal to the understanding of retinoblastoma pathway of cell cycle control as well as the transcriptional co-activation function of the key regulatory proteins, p300 and CBP. He is also credited with the landmark discovery of the central functions of the tumor suppressors, BRCA1 and BRCA2, which has revolutionized the fields of breast and ovarian cancer research. He will deliver his award lecture at the AACR Annual Meeting this April in Washington, DC.
Anjana Rao, PhD (Damon Runyon Fellow ’79), and James Scott-Browne, PhD (Damon Runyon Fellow ’11-’13), at the La Jolla Institute for Allergy and Immunology, La Jolla, and colleagues, are focusing on a key issue of how tumor-fighting T cells can lose their effectiveness or become “exhausted.” The researchers identified two proteins, NFAT and Nr4a, that can bind to the DNA of T cells and shut down their tumor-fighting activity. Next steps will be to determine if these processes can be interfered with or reversed in order to re-motivate immune cells to eradicate a patient's tumor. These results were published in the journal Proceedings of the National Academy of Science.
Christine Iok In Chio, PhD (Damon Runyon Shirley Stein Fellow ’13-’17), in the laboratory of her sponsor David Tuveson, MD, PhD, and colleagues at Cold Spring Harbor Laboratory, Cold Spring Harbor, created a new 3D model of pancreatic cancer, which allowed them to identify two distinct stroma cell populations called cancer-associated fibroblasts (CAF’s), that work together with cancer cells to protect and help the tumor grow. One reason pancreatic cancer is difficult to treat is the dense stromal tissue that envelops tumors and acts as a physical barrier that blocks drug delivery. Since CAFs secrete extracellular matrix, which surround the cancer cells and shape the stroma, CAFs are attractive targets for drug development of targeted therapies for pancreatic cancer. The findings were published in the Journal of Experimental Medicine.
Gregory L. Beatty, MD, PhD (Damon Runyon-Nadia’s Gift Foundation Innovator ’12-’15) and colleagues at the Abramson Cancer Center at University of Pennsylvania, Philadelphia, reported high levels of inflammatory compounds in mice with pancreatic tumors. These included CCL2, a signaling molecule that promotes recruitment of inflammatory white blood cells by tumors. This likely contributes to the protective tumor microenvironment that makes most pancreatic tumors resistant to treatment. CCL2 levels increased further after the mice received radiotherapy. However, treatment with chemo and a CCL2-blocking antibody resulted in dramatically slower tumor growth and reduced recruitment of inflammatory cell types. These treated mice survived roughly 25% longer than those that received radiation alone. The results were published in the journal Clinical Cancer Research.
Theodora S. Ross, MD, PhD (Damon Runyon Scholar ’01-’03), and colleagues at UT Southwestern, Dallas, reported that the BRCA1 gene is required for the survival of blood forming stem cells. This could explain why patients with BRCA1 mutations do not have an elevated risk for leukemia; the stem cells die before they have an opportunity to transform into a blood cancer. These results also suggest that these patients may be at higher risk for the serious side effects of chemotherapy. The study was published in Cell Reports.
Elaine V. Fuchs, PhD (Damon Runyon Board Member, Damon Runyon Fellow ‘77-‘79) of The Rockefeller University, New York, has been named the recipient of the 2017 McEwen Award for Innovation. The prize, given by the International Society for Stem Cell Research, recognizes groundbreaking work pertaining to stem cells or regenerative medicine. Dr. Fuchs studies adult skin stem cells, how they make and repair tissues, and how cancers develop.
Akinyemi I. Ojesina, MBBS, PhD (Damon Runyon Fellow ’08-’11), of University of Alabama at Birmingham, worked with The Cancer Genome Atlas Research Network to identify novel genomic and molecular characteristics of cervical cancer that will aid in the subclassification of the disease and may help define personalized therapies for each individual patient. The new study conducted a comprehensive analysis of the genomes of 178 primary cervical cancers, and found that more than 70 percent of the tumors had genomic alterations in either one or both of two important cell signaling pathways (PI3K/MAPK and TGF-beta). The researchers also found that a subset of tumors did not show evidence of human papillomavirus infection. Certain cervical cancers contained mutations in genes that normally put ‘brakes’ on the immune system, suggesting treatment with immunotherapy “checkpoint inhibitors” may be effective against these cancers. The report was published in the scientific journal Nature.
Pardis C. Sabeti, MD, DPhil (Damon Runyon Fellow ‘04-‘06) of Harvard University, Cambridge, will receive the 2017 Richard Lounsbery Award from the National Academy of Sciences. She is recognized for her groundbreaking contributions including the development of new methods to study evolutionary selection in humans and viruses; the creation of new collaborative models for combatting emerging diseases across disciplinary and national borders; and leadership of global efforts to increase data sharing in pandemics such as Ebola and Lassa Fever. She published landmark genomic studies describing Ebola virus transmission during the 2014 outbreak.
Elaine V. Fuchs, PhD (Damon Runyon Board Member, Damon Runyon Fellow ‘77-‘79) and Shruti Naik, PhD (Damon Runyon Fellow ’14-’18) at The Rockefeller University, New York, and colleagues, found that skin squamous cell carcinomas alter the protein-making machinery to preferentially use tumor-related mRNAs, leading to the production of proteins important for cancer progression. This switch is linked to a ribosome initiation factor called eIF2 and transition initiation factor eIF2A. The results suggest that these could represent new targets for anticancer drug development. The study was published in the scientific journal Nature.
Trudy G. Oliver, PhD (Damon Runyon-Rachleff Innovator ’13-’15), and colleagues at the Huntsman Cancer Institute at the University of Utah, Salt Lake City, reported the generation of a new mouse model for studying small cell lung cancer (SCLC). They demonstrated that Myc oncogene expression cooperates with Rb1 and Trp53 loss in the mouse lung to promote aggressive, highly metastatic tumors that are initially sensitive to chemotherapy followed by relapse. Targeted drug screening found that SCLC with high MYC expression is vulnerable to Aurora kinase inhibition, which, combined with chemotherapy, strongly suppresses tumor progression and increases survival. This study identified molecular features for patient stratification and uncovers a potential targeted treatment approach for these specific cancers. The study was published in Cancer Cell.
Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) of the Broad Institute, Cambridge, and colleagues, reported the discovery of new types of RNA-targeting CRISPR systems, which utilize a novel Cas enzyme called Cas13b. Cas13b is capable of targeting and degrading RNA (rather than DNA, which is targeted by previous CRISPR systems), which will enable researchers to specifically manipulate RNA in a high-throughput manner and manipulate gene function more broadly. The characterization of Cas13b has the potential to create a suite of RNA manipulation tools for studying a wide-range of biological processes that could be important for understanding and treatment of cancer and other diseases. The findings were reported in the scientific journal Molecular Cell.