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Major milestone reached in effort to identify the genetic roots of cancer
Researchers nationwide have reached a major milestone in describing the genetic landscape of cancer. Li Ding, assistant director of The McDonnell Genome Institute at Washington University, and scientists from about 20 other institutions have completed the genetic analyses of more than 11,000 tumors from patients, spanning 33 types of cancer - all part of The Cancer Genome Atlas (TCGA) project. Altogether, they identified about 300 genes that drive tumor growth. Remarkably, just over half of all tumors analyzed carry genetic mutations that could be targeted by therapies already approved for use in patients. Their findings are reported in six papers published April 5 in the journals Cell, Cell Reports and Cell Systems. WU Record 4/5/18
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Academy of Science-St. Louis honors Stuart Kornfeld
Stuart Kornfeld was honored on April 5 at a dinner at the Missouri Botanical Garden in recognition of his outstanding scientific contributions. Kornfeld's research has been instrumental in understanding the workings of lysosomal proteins, which must make their way to the cells' lysosomes in order to digest cellular parts and molecules that are no longer needed and help cells dispose of viruses and bacteria. Misdirected or malformed lysosomal proteins can lead to lysosomal storage diseases, such as Tay-Sachs disease and Niemann-Pick disease. WU Record 3/5/18
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Zika virus kills brain cancer stem cells
While Zika virus causes devastating damage to the brains of developing fetuses, it one day may be an effective treatment for glioblastoma, a deadly form of brain cancer. New research from the labs of Milan Chheda and Michael Diamond at Washington University and Jeremy Rich at UC San Diego shows that the virus kills brain cancer stem cells, the kind of cells most resistant to standard treatments. Journal of Experimental Medicine 2017 Sep 5 | WU Record 9/5/17 | Outlook Magazine winter 2017/18
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John DiPersio receives NCI outstanding investigator award
John DiPersio, Chief of the Division of Oncology, has received a $6 million outstanding investigator award from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) to support research aimed at improving therapies for leukemia. WU Record 11/6/17
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New gene-altering treatment offered for certain blood cancers
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved by the Food and Drug Administration (FDA) for types of advanced non-Hodgkin lymphoma in adults, the CAR-T cell therapy harnesses a patient’s own immune system to fight cancer. WU Record 10/18/17 | Center for Gene & Cellular Immunotherapy
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Chemo-loaded nanoparticles target breast cancer that has spread to bone
Seeking new treatments for metastatic breast cancer, Kathy Weilbaecher and colleagues have designed nanoparticles that carry chemotherapy and are targeted directly to tumors that have spread to bone. The strategy, developed in mouse studies, lets chemotherapy penetrate the protective environment of bone and minimizes toxic side effects. Cancer Research 2017 Aug 30 | WU Record 9/25/17
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CRISPR sheds light on rare pediatric bone marrow failure syndrome
Children with dyskeratosis congenita - characterized by short telomeres - experience progressive bone marrow failure, eventually losing the ability to make red blood cells, white blood cells and platelets. Luis Batista, Chris Sturgeon and co-workers used CRISPR to edit into human embryonic stem cells two mutations associated with the disease to produce a novel model of the disorder. They showed how blocking the downstream effects of these mutations can lead to normal production of blood cells. Stem Cell Reports 2017 Aug 8 | WU Record 7/27/17
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Rogue breast tumor proteins point to potential drug therapies
Studying mice with breast tumors transplanted from patients, a group at Washington University led by Li Ding, in collaboration with colleagues at The Broad Institute of MIT and Harvard and Baylor College of Medicine, have analyzed the proteins present in these tumors. The researchers demonstrated that some protein alterations can be used to identify drugs that may work against some cancers. Nature Communications 2017 Mar 28 | WU Record 3/28/17
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Online database aims to collect, organize research on cancer mutations
A group led by Obi and Malachi Griffith has developed an online "knowledgebase" to gather and organize information on cancer genomics, providing an educational forum for dissemination of information and discussion of the clinical significance of cancer genome alterations. The online resource, called CIViC, for Clinical Interpretations of Variants in Cancer, is open to anyone who wants to contribute or make use of the information. Submissions are curated by editors and moderators who are experts in the field. Nature Genetics 2017 Jan 31 | WU Record 1/30/17
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Study unveils new way to starve tumors to death
Many sarcomas lack an enzyme required for production of arginine, an essential component of most proteins, but attempts to kill the tumor cells by starving them of this nutrient have been unsuccessful. After analyzing the complex metabolism of these tumors, Brian Van Tine, Jason Held, and co-workers discovered that adding a glutamine inhibitor to an arginine-depleting drug killed the cells and caused tumor regression in mice. These results form the basis of a planned clinical trial in patients with sarcomas. Cell Reports 2017 Jan 24 | WU Record 1/24/17
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In highly lethal type of leukemia, cancer gene predicts treatment response
Patients with the most lethal form of acute myeloid leukemia (AML) – based on genetic profiles of their cancers – typically survive for only four to six months after diagnosis, even with aggressive chemotherapy. But new research by John Welch and colleagues in the Oncology Division indicates that such patients, paradoxically, may live longer if they receive a milder chemotherapy drug. N Engl J Med 2016 Nov 24 | WU Record 11/28/16
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New immunotherapy for leukemia shows promise in small clinical trial
A new type of immunotherapy shows promise against cases of acute myeloid leukemia (AML) that recur after treatment or that never respond to therapy in the first place. A small clinical trial conducted by Rizwan Romee and Todd Fehniger provides evidence that the immune system’s "natural killer" cells can be dialed up in the laboratory, trained to recall that activation and then effectively unleashed to destroy cancer cells in some patients. Science Translational Medicine 2016 Sep 21 | WU Record 9/21/16
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Study finds marker of aggressive prostate cancer
The level of an RNA molecule (PCAT-14) expressed in prostate tumors is an indicator of whether the cancer is likely to spread, according to research published by Chris Maher and colleagues. Down-regulation of PCAT-14 is associated with a greater probability of metastatic progression, and this finding may help to determine the intensity of therapy in individual patients. European Urology 2016 Jul 22 | WU Record 8/2/16
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2016 Employee Recognition Awards
Thirty-four employees in the Divisions of Hematology and Oncology were recognized at the 2016 Department of Medicine Length of Service Awards Ceremony for service to the department spanning 10 to 40 years. In addition, Bob Barczewski, Director of Business Operations for the Division of Oncology, received the annual Dean’s Distinguished Service Award. List and photos of awardees
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2016 Dr. Adel A. Yunis Awards for Research Excellence
The Hematology Division is pleased to announce the recipients of the 2016 Dr. Adel A. Yunis Awards for Research Excellence. These awards recognize outstanding postdoctoral fellows, house staff or students conducting basic research in molecular hematology. This year the recipients are Wilson C. Fok, Ph.D., and Alexandre T. Vessoni, Ph.D. Both awardees are postdoctoral fellows in the laboratory of Luis Batista, Ph.D.
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Study seeks clues to breast cancer outcomes in African-American women
Foluso Ademuyiwa and her colleague Laura Beirut (Department of Psychiatry) are launching a major study in African-American women with breast cancer to learn whether their genetic risks are influenced by the same mutations that affect white women or are altogether different mutations. Such information may lead to new ways to prevent or treat breast cancer in African-American women. WU Record 7/29/16
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Immune-based therapy in mice shows promise against pancreatic cancer
David DeNardo, Andrea Wang-Gillam and their colleagues have shown that immunotherapy against pancreatic cancer can be effective when given in conjunction with focal adhesion kinase (FAK) inhibitors, drugs that break up the fibrous tissue in these tumors. A phase 1 clinical trial to test the safety of FAK inhibitors in patients with advanced pancreatic cancer is underway. Nature Medicine 2016 Jul 4 | WU Record 7/5/16
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Probing proteins' 3-D structures suggests existing drugs may work for many cancers
Examining databases of proteins’ 3-D shapes, a group led by Li Ding has identified more than 850 DNA mutations that appear to be linked to cancer. The information may expand the number of cancer patients who can benefit from existing drugs. Nature Genetics 2016 Jun 13 | WU Record 6/13/16
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Tim Ley to receive the 2016 Carl and Gerty Cori Faculty Achievement Award
Tim Ley is being recognized for his pioneering research in cancer genomics. His studies have laid the groundwork for precision medicine in cancer, which targets treatment to a patient based on the genetic makeup of a tumor and how it responds to therapy. WU Record 5/18/16
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Express Scripts contributes to cancer care in north St. Louis County
To help improve access to cancer specialists for underinsured residents of north St. Louis County, Express Scripts, a leading pharmacy benefit management company, has donated $200,000 to Washington University to establish the Express Scripts North County Oncology Fund. Proceeds will provide greater access to specialty care and treatments, including clinical trials, at Christian Hospital on Dunn Road. WU Record 4/6/16
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Govindan named Anheuser-Busch Endowed Chair in Medical Oncology
Ramaswamy Govindan has been named the Anheuser-Busch Endowed Chair in Medical Oncology. The Anheuser-Busch Foundation established the endowed chair in 2001. Govindan was honored for his innovative research, including in genomics, aimed at developing better lung cancer therapies and improving patient outcomes. WU Record 2/17/16
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Study uncovers hard-to-detect cancer mutations
Li Ding and co-workers developed a software tool for finding a certain type of genetic error that has been consistently missed by cancer genome studies. These "complex indels" appear to cluster in important cancer genes more often than can be attributed to random chance. Patients may benefit when indels are found in genes that already have drugs designed to counter the effects of mutation. Nature Medicine 2016;22:97 | WU Record 1/5/16
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Hematology-oncology faculty members receive scholar awards
Luis Batista and Grant Challen have received 2015 V Scholar Grants from the V Foundation for Cancer Research to support their work on telomerase RNA in dyskeratosis congenita and novel tumor supressors in chronic myeloid neoplasms. Chris Sturgeon and Steve Oh are recipients of 2016 Scholar Awards from the American Society of Hematology.
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Tim Ley receives $6.4 million NCI award for leukemia research
Tim Ley, Director of the Stem Cell Biology Section in the Division of Oncology, received a seven-year, $6.4 million Outstanding Investigator Award from the National Cancer Institute of the National Institutes of Health. The funding allows him to continue research aimed at understanding the mutations that initiate acute myeloid leukemia. WU Record 10/22/15
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Relapse in AML is linked to genetic mutations that persist in remission
Using genetic profiling to study bone marrow samples from patients with acute myeloid leukemia (AML), Tim Ley and colleagues found that those whose cells still carried mutations 30 days after the initiation of chemotherapy were about three times more likely to relapse and die than patients whose bone marrow was cleared of these mutations. JAMA 2015;314:811 | WU Record 8/25/15
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Siteman Cancer Center earns highest rating from the NCI
The National Cancer Institute (NCI) has awarded Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis an “exceptional” rating, based on a rigorous review of Siteman’s research programs. The rating is the highest possible by the NCI, the principal federal institute that funds cancer research. WU Record 7/7/15
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New technology may reduce deadly complication of bone marrow transplants
Linda Eissenberg, John DiPersio, and their colleagues have developed a new approach to mitigate graft-versus-host disease. In a pilot study, they showed that donor T cells genetically modified to contain a suicide switch can be administered safely to patients with leukemia. The desired result of donor T cell administration is to produce a graft-versus-leukemia effect. If the donor T cells expand and cause severe graft-versus-host disease, however, they can be killed by turning on the suicide switch with ganciclovir. Mol Ther 2015;23:1110 | WU Record 5/11/15
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Medical students honor faculty
Each year, medical students express appreciation for their teachers’ efforts by selecting the course masters, lecturers, clerkship directors, attendings and residents who distinguished themselves most in educating students. Among this year's recipients of the Distinguished Service Teaching Awards are Scot Hickman of the Hematology Division and Jason Weber of the Oncology Division (Molecular Oncology Section). WU Record 12/11/14
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Genetic errors linked to aging underlie leukemia that develops after cancer treatment
Terrence Wong, a hematology-oncology fellow working in Dan Link's laboratory, found that mutations that accumulate randomly as a person ages can play a role in a fatal form of leukemia that develops after treatment for another cancer. This study, which was done in collaboration with colleagues in the Oncology Division and The Genome Institute at Washington University, challenges the view that cancer treatment in itself is a direct cause of therapy-related AML. Nature 2015;518:552 | WU Record 12/8/14
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Many older people have mutations linked to leukemia or lymphoma in their blood cells
Analyzing blood samples from subjects enrolled in The Cancer Genome Atlas project, Li Ding and co-workers discovered that 5 percent of people over age 70 harbor mutations linked to leukemia and lymphoma. Since the incidence of these disorders is less than 0.1 percent among the elderly, additional research is needed to determine whether these mutations increase the risk of developing a hematologic malignancy. Nature Medicine 2014;20:1472 | WU Record 10/19/14
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ASH recognizes John DiPersio for outstanding mentorship
The American Society of Hematology (ASH) will honor Grover C. Bagby Jr., MD, and John F. DiPersio, MD, PhD, with 2014 Mentor Awards at the 56th ASH Annual Meeting and Exposition in San Francisco for their sustained, outstanding commitment to the training and career development of early-career hematologists. ASH Press Release 7/22/14
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Stephen Oh named Doris Duke-Damon Runyon Clinical Investigator
Steve Oh is one of seven new Damon Runyon Clinical Investigators. The recipients of this prestigious three-year award are outstanding early career physician-scientists conducting patient-oriented cancer research at major research centers under the mentorship of the nation's leading scientists and clinicians. Each will receive $450,000 to support the development of his/her cancer research program. Dr. Oh aims to investigate the cellular abnormalities that underlie myeloproliferative neoplasms. Damon Runyon Cancer Research Foundation 6/23/14
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Lung cancer study hints at new treatments
Ramaswamy Govindan and collaborators in The Cancer Genome Atlas Research Network have discovered mutations in the RTK/RAS/RAF signaling pathway that are present in about 75% of patients with adenocarcinoma of the lung. The new findings may expand treatments for this disease, because drugs targeting some of these genetic changes already are available or are in clinical trials. Nature 2014;511:543 | WU Record 7/9/14
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Some aggressive cancers may respond to anti-inflammatory drugs
Jason Weber's laboratory has found that triple-negative breast cancer cells lacking the tumor suppressor proteins p53 and ARF turn on a JAK-dependent pathway involved in the innate immune response to viral infection. This antiviral response may create a local environment of inflammation that supports more aggressive tumors. The study suggests that some patients may benefit from JAK inhibitors, a class of anti-inflammatory drugs currently prescribed for rheumatoid arthritis. Cell Reports 2014;7:514 | WU Record 6/26/14
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New center aims to use immune system to fight cancer, other diseases
A laboratory within the Center for Human Immunology and Immunotherapy Programs (CHiiPs) will monitor changes in the immune system during clinical trials of new immunotherapies. The centerpiece of the laboratory, directed by Steve Oh, is a state-of-the-art instrument known as a time-of-flight mass cytometer that simultaneously can detect more than 50 different structures either on the cell surface or inside the cell. WU Record 4/17/14
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Journal honors breast cancer researcher
The Journal of Biological Chemistry has recognized Ron Bose and his colleagues for their work describing the combined structure of two proteins (HER2 and HER3) that, when bound together, drive growth of many breast cancers. This work was chosen as JBC's best signal transduction article of 2013. J Biol Chem 2013;288:25254 | WU Record 3/27/14
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Surprising culprit found in cell recycling defect
Members of Stuart Kornfeld's laboratory have identified an unusual cause of the lysosomal storage disorder called mucolipidosis III. They found that a phosphotransferase, which is responsible for adding the targeting signal to lysosomal enzymes, seems to lack a mechanism that keeps it properly localized in the Golgi apparatus. PNAS 2014;111:3532 | WU Record 3/12/14
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Study shows 1 in 5 women with ovarian cancer has inherited predisposition
A new study by Li Ding and colleagues estimates that about 20% of women with ovarian cancer have inherited genetic mutations associated with increased risk, even though most of these women do not have strong family histories of the disease. The research is the first large-scale analysis of the combined contributions of inherited and acquired mutations in a major cancer type. Nature Communications 2014;5:3156 | WU Record 2/22/14
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Lee Ratner named Wolff Professor of Oncology
Lee Ratner's primary research interest focuses on retroviruses, including the human T-cell leukemia virus type 1, which causes a specific form of lymphoma, and the human immunodeficiency virus (HIV) associated with AIDS. His studies have been applied to developing novel therapeutic approaches for these viral infections. WU Record 11/7/13
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Evan Sadler elected to the Institute of Medicine
Evan Sadler, chief of the Division of Hematology, has been elected to the Institute of Medicine of the National Academy of Sciences, one of the highest honors medical scientists in the United States can receive. The Institute of Medicine serves as a national resource for independent analysis and recommendations on issues related to medicine, biomedical sciences and health. WU Record 10/21/13
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Genetic errors identified in 12 major cancer types
Li Ding and co-workers have identified 127 repeatedly mutated genes that appear to drive the development and progression of a range of tumors. For example, a gene mutated in 25 percent of leukemia cases also was found in tumors of the breast, rectum, head and neck, kidney, lung, ovary and uterus. The discovery sets the stage for devising new diagnostic tools and more personalized cancer treatments. Nature 2013;502:333 | WU Record 10/16/13
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Database of disease genes shows potential drug therapies
Obi Griffith and his twin brother Malachi, working with colleagues at The Genome Institute, have created an online database that matches genes linked to cancer and other diseases with drugs that target those genes. The database includes more than 14,000 drug-gene interactions involving 2,600 genes and 6,300 drugs. Another 6,700 genes are in the database because they potentially could be targeted with future drugs. Nature Methods 2013;10:1209 | WU Record 10/13/13
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Discovery helps show how breast cancer spreads
Working in mouse models of breast cancer and breast tumor samples from patients, Greg Longmore and his colleagues showed that a protein on the surface of tumor cells, called DDR2, binds to collagen and activates a multistep pathway that encourages tumor cells to spread. This finding may explain why women with dense breasts are at increased risk for invasive breast cancer. Nature Cell Biology 2013;15:677 | WU Record 5/5/13
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Distinct niches in bone marrow nurture blood stem cells
In research that one day could improve the success of stem cell transplants and chemotherapy, Dan Link and co-workers have found that distinct niches exist in bone marrow to nurture different types of blood stem cells. The new findings, in mice, suggest that it may be possible to therapeutically target support cells in a particular niche. Nature 2013;495:227 | WU Record 2/24/13
Center for Gene & Cellular Immunotherapy (CGCI):
CAR T-Cell Immunotherapy Offered to Patients with Advanced Lymphoma
Clinical trials at Wash U of CAR T-cell therapy for leukemia, multiple myeloma and ovarian cancer are also underway or will soon begin.
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In Memoriam
H. Jean Khoury (5/22/17)
Faculty Profile:
Ramaswamy Govindan
