2008 New Discoveries and Honors in Cancer Research
Members of the Damon Runyon scientific circle regularly publish findings on the latest cancer research and are frequently recognized for their contributions to the fight against cancer. Below, you will find new discoveries in cancer research and the most recent honors bestowed upon Damon Runyon Cancer Research Foundation awardees, alumni and friends.
December 26, 2008
Erik W. Debler, PhD (Damon Runyon Fellow '08-'10) and colleagues at The Rockefeller University, New York, reported the crystal structure of core proteins in the nuclear pore complex (NPC). The NPC is a large protein complex that is essential for regulating the movement of proteins into and out of the cell’s nucleus. Identifying the structure of NPC proteins allows the researchers to propose a model for how the NPC functions. Defects in the assembly, structure and function of the NPC can lead to diseases such as cancer and viral infections. A better understanding of how the complex works could lead to new treatments for these diseases. This work was featured on the cover of the journal Molecular Cell.
December 15, 2008
Renier J. Brentjens, MD, PhD (Damon Runyon-Lilly Clinical Investigator '06-'09) and colleagues at the Memorial Sloan-Kettering Cancer Center, New York, reported the success of a novel therapy regimen in Chronic Lymphocytic Leukemia (CLL) patients. Previously untreated CLL patients were sequentially treated with the chemotherapeutic fludarabine, followed by chemotherapeutic drug cyclophosphamide, then the targeted therapy rituximab/Rituxan (a monoclonal antibody that destroys B lymphocytes). This treatment achieved an impressive positive response in 89% of patients, with a markedly improved 5-year survival rate of 71% compared with 48% survival for patients treated with chemotherapy alone. These results were published in the Journal of Clinical Oncology.
December 12, 2008
Rafael Fonseca, MD (Damon Runyon-Lilly Clinical Investigator '00-'05) and colleagues at the Mayo Clinic, Rochester, reported that a new combination of medications improved or stabilized multiple myeloma for 76 percent of patients who had relapsed after previous treatment. In interim results of an ongoing clinical trial evaluating pomalidomide, a new immunomodulatory agent, combined with dexamethasone (pom/dex), the researchers saw good results with less toxicity. Immunomodulatory drugs work by interfering with cancer cell growth and by stimulating the immune system to attack the cancer cells. The results were reported at the American Society of Hematology meeting.
Robert H. Singer, PhD (Damon Runyon Fellow '70-'72) and colleagues at the Albert Einstein College of Medicine, Bronx, described a powerful new "single RNA counting" technique that allows individual mRNA molecules within single cells to be counted. This level of detail will help answer questions about how much of a gene is made over time and how much that level varies from cell to cell. This could advance the understanding of mechanisms that trigger cancer, which arises when gene regulation and function go awry. These findings were published in the journal Nature Structural and Molecular Biology.
December 8, 2008
At the American Society of Hematology meeting, Colleen Delaney, MD, MSc (Damon Runyon-Novartis Clinical Investigator '07-'10) of the Fred Hutchinson Cancer Research Center, Seattle, reported the success of a new approach of expanding blood cells from donated umbilical cords. She cultured cord blood with a Notch pathway ligand and cytokines to increase the number of CD34+ stem cells prior to transplantation; this decreased the time required for the transplanted cells to engraft and begin production of healthy blood cells in patients with acute myeloid leukemia. Her results could help increase the success rates of cord blood stem cell transplants by shortening the time during which patients have low white-cell counts that leave them susceptible to life-threatening infections.
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The story of one of Dr. Delaney's patients who is benefitting from this new approach was recently featured in an article in The Australian: "Stem cells give leukemia patient a second chance."
Joan Massagué, PhD (Fellowship Award Committee '92-'96, Former Sponsor) of Memorial Sloan-Kettering Cancer Center, New York, was selected to receive the AACR Distinguished Leadership Award in Breast Cancer Research. His research identified the critical role of transforming growth hormone factor-Beta (TGF-Beta) in the metastasis of breast cancer cells to the lung.
December 2, 2008
Sriram Subramaniam, PhD (Damon Runyon Fellow '87-'90) and his team at the National Cancer Institute’s (NCI) Center for Cancer Research Laboratory of Cell Biology, Bethesda, were recently profiled in the NCI Cancer Bulletin. They are developing tools and strategies for high resolution imaging of cells and viruses, particularly HIV and cancer. His group recently won an award for the image of a melanoma cell and published 3D images of the structures HIV uses to enter cells, created with electron tomography. These novel imaging techniques will enable scientists to answer questions that they previously lacked the technology to address.
November 20, 2008
Sarkis K. Mazmanian, PhD (Damon Runyon-Rachleff Innovator '08-'10) of the California Institute of Technology, Pasadena, was named one of the 50 Best Brains in Science by Discover magazine. He was included in the "20 under 40" list, which highlights "a new generation of innovators changing the way we think about everything from theoretical mathematics to cancer therapy." Sarkis is developing the novel hypothesis that intestinal bacteria are a critical factor in colon cancer.
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November 19, 2008
The American Cancer Society announced the recipients of its highest honor, the Medal of Honor. This year's winners are: The Honorable Edward M. Kennedy, United States Senator from Massachusetts, for Cancer Control; Mina J. Bissell, PhD, for Basic Research; Susan Band Horwitz, PhD (Former Damon Runyon Clinical Investigator Mentor) of Albert Einstein College of Medicine, for Clinical Research; and Jon M. Huntsman for Cancer Philanthropy. All are being recognized for their outstanding contributions to the fight against cancer.
November 17, 2008
Lu Gan, PhD (Damon Runyon Fellow '07-'09) and colleagues at the California Institute of Technology, Pasadena, described the first 3D visualization of the cell-wall structure of bacteria. They used high-tech microscopy techniques that enabled the scientists to visualize these biological structures at nanometer resolution. They found that the cell-wall structure is made up of a mesh-like structure of carbohydrates (glycans) and amino-acid peptides. This structure is targeted by the antibiotic penicillin, blocking a bacterium's ability to grow. These findings lead to a better understanding of how a bacterium directs its own growth, and how drugs that block that process might work.
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November 3, 2008
Scott A. Armstrong, MD, PhD (Damon Runyon-Lilly Clinical Investigator '03-'08) and colleagues at the Children's Hospital, Boston, and the Dana-Farber Cancer Institute, Boston, identified a novel mechanism that underlies a form of acute lymphoblastic leukemia (ALL) known as MLL-AF4. This form of disease makes up 70 percent of ALLs striking infants, who suffer rapid relapses and are cured at a rate of under 50 percent with chemotherapy. Using a new mouse model of MLL-AF4, they found that the defective protein (also called MLL-AF4) giving rise to the disease abnormally modifies a histone protein; this alters chromosome structure and results in gene activation and initiation of leukemia. In these studies, the researchers also identified an enzyme called DOT1L, which acts in partnership with MLL-AF4. Enzymes like DOT1L can be targeted with small-molecule drugs, resulting in inhibition of critical genes that contribute to malignancy. In general, reversal of histone modifications could be an important therapeutic approach for a variety of cancer types. This work was published in the journal Cancer Cell.
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Maura L. Gillison, MD, PhD (Damon Runyon-Lilly Clinical Investigator '00-'05) of The Johns Hopkins University School of Medicine, Baltimore, and colleagues reported the results of the first comprehensive epidemiological study of human papillomavirus (HPV)-associated cancer data in the US. In an analysis of data from 1998-2003, they identified 25,000 cancer cases per year at cancer sites associated with HPV infection. Of these, the researchers determined that HPV infection is the underlying cause of 80% or 20,000 of the cancers. These findings, which were reported in a Centers for Disease Control and Prevention (CDC) monograph, suggest a growing need for HPV vaccination in both women and men for cancer prevention. In a second study published in the journal Clinical Cancer Research, Dr. Gillison and team demonstrated that simple "swish and spit" saliva rinses are able to detect oral HPV infection in patients and that this infection is more frequent in those with HPV-positive head and neck cancer. This represents a simple way to monitor HPV infection over time to identify those at risk of developing cancer or cancer recurrence.
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October 13, 2008
Election to the Institute of Medicine is one of the highest honors that can be earned in the fields of medicine and health. In recognition of their outstanding achievements, 10 members of the Damon Runyon Cancer Research Foundation circle were inducted this October:
Kathryn V. Anderson, PhD (Fellowship Award Committee Member '96-'99, Scholar Award Panel Member '03-'05, Former Damon Runyon Sponsor), Memorial Sloan-Kettering Cancer Center, New York, New York
Sanjiv Sam Gambhir, MD, PhD (Innovation Award Committee Member), Stanford University, Stanford, California
Douglas Hanahan, PhD (Former Damon Runyon Sponsor), University of California, San Francisco, California
Arthur L. Horwich, MD (Former Damon Runyon Sponsor), Yale University School of Medicine, New Haven, Connecticut
John W. Kappler, PhD (Former Damon Runyon Sponsor), National Jewish Health Center, Denver, Colorado
Raju S. Kucherlapati, PhD (Damon Runyon Grantee '73-'74), Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts
Philippa Marrack, PhD (Damon Runyon Fellow '71-'73 and Fellowship Award Committee Member), National Jewish Health Center, Denver, Colorado
John E. Niederhuber, MD (Damon Runyon Grantee ‘75-‘76), National Cancer Institute, National Institutes of Health, Bethesda, Maryland
David C. Page, MD (Former Damon Runyon Sponsor), Whitehead Institute for Biomedical Research, Cambridge, Massachusetts
Charles L. Sawyers, MD (Former Damon Runyon Clinical Investigator Mentor), Memorial Sloan-Kettering Cancer Center, New York, New York
October 9, 2008
Julien Sage, PhD (Damon Runyon Scholar '05-'07) and colleagues at Stanford University, Stanford, have discovered how the tumor suppressor family retinoblastoma (Rb) proteins affect stem cells. Removing Rb function resulted in overproliferation of a subclass of blood stem cells (myeloid cells); these actively-diving cells were also unable to repopulate the immune system in a mouse model of bone marrow transplantation. The researchers’ results indicate a critical role for Rb in suppressing tumors originating in stem cell populations, such as blood cancers. These findings were published in the journal Cell Stem Cell.
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October 8, 2008
Martin Chalfie, PhD, of Columbia University, New York, and Roger Y. Tsien, PhD, of the University of California, San Diego, (both Former Damon Runyon Sponsors) were awarded the Nobel Prize in Chemistry for 2008 "for the discovery and development of the green fluorescent protein, GFP.” They shared the award with Osamu Shimomura, PhD, of Marine Biological Laboratory, Woods Hole, who originally isolated the protein from jellyfish. Dr. Chalfie first demonstrated the use of GFP as a genetic tag to visualize specific cells in the body. Dr. Tsien contributed to the understanding of how GFP fluoresces and developed numerous colors of related fluorescent proteins that allow scientists to visualize multiple proteins and cells at the same time. GFP enables researchers to watch cellular processes that were previously invisible, such as development of cells in an embryo and metastasis of cancer cells.
Mark J. Zylka, PhD (Damon Runyon Fellow '00-'03) and colleagues at the University of North Carolina, Chapel Hill, have discovered a new target for pain control. The protein, prostatic acid phosphatase or PAP, acts in pain-sensing neurons and appears to suppress pain eight times more effectively than the commonly-used drug morphine. Zylka hopes that these findings, which were published in the journal Neuron, will lead to new improved treatments for pain.
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October 5, 2008
In the journal Nature, Ken Cadwell, PhD (Lallage Feazel Wall Fellow '08-'11) and colleagues at Washington University, St. Louis, reported findings correlating the cellular process of autophagy to Crohn’s disease, an inflammatory bowel disorder. They studied a Crohn’s-associated gene called ATG16L1 and found that it functions in Paneth cells, immune cells in the lining of the small intestine. These cells make proteins and antimicrobial peptides that they package as granules and secrete into the intestine to protect the body against infection. This secretion is defective in the Paneth cells of Crohn’s disease patients that lack ATG16L1. This new understanding of the causes underlying Crohn’s disease may also be important for prevention of colorectal cancer, as the two diseases can be linked.
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September 30, 2008
Robert Tjian, PhD (Former Damon Runyon Sponsor) of the University of California, Berkeley, has been elected the new president of the Howard Hughes Medical Institute (HHMI).
He is a distinguished biochemist and long-time HHMI investigator, who
will assume his new role on April 1, 2009. He will succeed Thomas R. Cech, PhD
(Former Damon Runyon Sponsor) who has served as HHMI's president since
January 2000. Cech recently announced his decision to step down from
the presidency in order to return to full-time research and teaching at
the University of Colorado, Boulder.
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September 22, 2008
The National Institutes of Health (NIH) awarded 16 Pioneer Awards and 31 New Innovator Awards to support innovative research with the potential to transform biomedical science. Each Pioneer Award provides $2.5 million over five years and can be received by scientists at any career level. Each New Innovator Award provides $1.5 million over five years to early career scientists who have not yet held an R01 grant. We congratulate the following Damon Runyon scientists:
James K. Chen, PhD (Damon Runyon Fellow '99-'02)
NEW INNOVATOR AWARDS
Ronald J. Buckanovich, MD, PhD (Damon Runyon Clinical Investigator '08-'11)
William M. Shih, PhD (Damon Runyon Fellow '01-'04)
Jue D. Wang, PhD (Damon Runyon Fellow '03-'06)
Lei Wang, PhD (Damon Runyon '03-'05)
September 15, 2008
Victor R. Ambros, PhD (Fellowship Award Committee Member, Former Sponsor) of the University of Massachusetts Medical School, Worcester, Gary B. Ruvkun, PhD (Current Sponsor, Former Fellowship Award Committee Member) of Massachusetts General Hospital and Harvard Medical School, Boston, and David C. Baulcombe, PhD, of the University of Cambridge, were announced as this year’s recipients of the highly prestigious Albert Lasker Medical Research Awards. They are being honored for their discovery of tiny RNAs (microRNAs) that regulate gene function in animals and plants and are implicated in a wide range of diseases including cancer. The Awards were presented at a ceremony on September 26 in New York City.
Rachael A. Clark, MD, PhD (Damon Runyon Clinical Investigator '08-'11) of Brigham and Women’s Hospital, Boston, and colleagues reported the mechanism by which squamous cell carcinomas (SCCs) evade the immune system. The researchers found that 1) SCCs do not express E-selectin, a molecule that normally functions to recruit immune cells during inflammation, and 2) SCCs recruit regulatory T (T reg) cells, which block the activity of anti-tumor T cells. Treatment with the drug imiquimod, an immune system activator, reverses these effects, supporting its use as a treatment for SCCs and other evasive tumor types. These findings were published in the Journal of Experimental Medicine.
September 11, 2008
Jeremy N. Rich, MD (Damon Runyon-Lilly Clinical Investigator '04-'09) of the Duke University Medical Center, was featured in the cover article of this week’s The Economist: “Cancer stem cells: The root of all evil?” Dr. Rich studies a type of brain cancer called glioblastoma. He has found that the cancer stem cells in these tumors are resistant to radiation therapy; while other cells in the tumor are killed by radiation, the stem cells survive because they are able to efficiently repair the radiation-induced DNA damage. In a mouse model of the disease, he was able to successfully kill the cancer stem cells by treatment with both radiation and a drug that disrupts DNA repair. In the near future, he hopes to test this treatment in human patients.
September 5, 2008
Pierre P. Massion, MD (Damon Runyon-Lilly Clinical
Investigator '03-'08) of Vanderbilt University, Nashville,
and colleagues identified a panel of genetic alterations (“genomic
signature”) that correlates with smoking history and non-small cell
lung cancer. These findings may indicate new genetic pathways involved
in lung cancer development that can be targeted for early detection and
prevention. The work was published in American Journal of Respiratory and Critical Care Medicine.
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September 4, 2008
Led in part by Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow '95-'98) of the Dana-Farber Cancer Institute, Boston, The Cancer Genome Atlas (TCGA) project reported the first results of their analysis of genetic alterations in glioblastoma brain tumors. In parallel studies, teams led by The Johns Hopkins University, Baltimore, examined more than 20,000 genes in pancreatic tumors [guided by Kenneth W. Kinzler, PhD (Innovation Award Committee Member)] and glioblastoma tumors. This work revealed the complexity of cancer: no tumors were identical, and each tumor contained 60 genetic alterations on average. Genes work together in pathways, so identifying the pathways affected by genetic alterations is critical. The groups reported three core pathways abnormal in most glioblastoma and 12 core pathways in most pancreatic tumors. This new understanding of cancer genetics could lead to more effective therapies and diagnostics. These findings were published in three separate studies in the journals Nature and Science.