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Structure of a key enzyme reveals the mechanism for lysosomal protein targeting
Cells synthesize 60 to 70 lysosomal hydrolases that must be delivered to the lysosome to allow proper functioning of this organelle. Critical for this process is the enzyme GlcNAc-1-phosphotransferase which specifically adds a Man-6-P tag to the lysosomal hydrolases that directs the cell’s transport machinery to deliver the hydrolases to the lysosome. Now, Wang-Sik Lee and Stuart Kornfeld, in collaboration with Huilin Li at the Van Andel Institute, show how this enzyme discriminates between the lysosomal hydrolases and numerous other secreted glycoproteins having identical glycan chains, thereby ensuring that only the former acquire the Man-6-P tag. Nat Struct Mol Biol 2022 Mar 24
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Stuart Kornfeld receives Roscoe O. Brady Award
Stuart A. Kornfeld, MD, the David C. and Betty Farrell Distinguished Professor of Medicine at Washington University School of Medicine, has received the 2022 Roscoe O. Brady Award for Innovation and Accomplishment from the WORLDSymposium (WORLD is an acronym for We’re Organizing Research on Lysosomal Diseases), a research conference dedicated to lysosomal diseases. WU Medicine News
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Novel treatment makes pancreatic cancer susceptible to immunotherapy
A recent study led by Kian-Huat Lim suggests that blocking IRAK4, a major inflammatory pathway that is activated in pancreatic cancer, makes the tumors sensitive to chemotherapy and a type of immunotherapy that prompts the immune system’s T cells to attack the cancer cells. The therapy more than doubled survival in a mouse model of pancreatic cancer. Haeseong Park is the principal investigator of a new clinical trial of the IRAK4 inhibitor in patients with pancreatic cancer. WU Record 3/7/22 | Gastroenterology 2022 Mar 7
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Boosting T cells improves survival in mice with glioblastoma
Glioblastoma, an aggressive cancer in the brain or spinal cord, has proven stubbornly resistant to radiation, chemotherapy, and newer immunotherapies, with fewer than 10% of patients surviving longer than five years after diagnosis. A new study conducted by Jian Campian, Milan Chheda and colleagues shows that treatment with the immune-boosting protein interleukin 7 (IL-7) in combination with radiation improves survival in mice with glioblastoma. The new mouse study shows that IL-7 increases the number of T cells in the tumor and other immune organs, which then attack the cancer cells and improve survival. WU Record 1/14/22 | Clin Cancer Res 2022 Jan 14
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Drug makes pancreatic cancer cells more vulnerable
An aggressive chemotherapy regimen is the first-line treatment for pancreatic cancer, but the side effects can be severe, and many tumors stop responding to treatment. Now, Patrick Grierson and Kian-Huat Lim have identified an anti-inflammatory drug, ATI-450, that makes pancreatic cancer cells more vulnerable to chemotherapy. Studying mice, they found that the drug also may reduce some of the damaging side effects of the chemotherapy cocktail FOLFIRINOX (a combination of folinic acid, 5-fluorouracil, irinotecan and oxaliplatin), commonly used to treat pancreatic cancer. WU Record 12/1/21 | Sci Transl Med 2021 Dec
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Elaine Majerus and Stephen Oh named co-chiefs of the Division of Hematology
Elaine M. Majerus, MD, PhD and Stephen T. Oh, MD, PhD, have been named co-Chiefs of the Division of Hematology in the Department of Medicine, effective December 1, 2021. Dr. Majerus will be responsible for the clinical operations, clinical research and clinical training aspects and Dr. Oh will be responsible for the basic and translational research aspects of the Division. Department of Medicine News
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New technique may lead to safer stem cell transplants
John DiPersio and colleagues have developed a method of stem cell transplantation in mice that does not require radiation or chemotherapy. Their strategy combines the targeted elimination of blood-forming stem cells in the bone marrow with immune-modulating drugs to prevent the immune system from rejecting the new donor stem cells. With the new technique, mice underwent successful stem cell transplants from unrelated mice without evidence of dangerously low blood cell counts that are a hallmark of the traditional procedure. WU Record 11/10/21 | J Clin Invest 2021 Nov 2
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$7.5 million to study elusive cell type important in aging, cancer, other diseases
Washington University is joining a new NIH research network focused on the study of senescent cells, a rare population of cells that are vital for understanding diseases of aging, including cancer and neurodegeneration. The Washington University Senescence Tissue Mapping Center, led by principal investigator Li Ding will map out senescent cells in bone marrow and liver samples in an effort to understand their spatial distribution and molecular signature in different tissue environments and at different ages. WU Record 10/20/21
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African American cancer patients less likely to receive genetic counseling
Foluso Ademuyiwa and her colleagues have surveyed oncologists to identify differences in physician attitudes that may contribute to a gap in referrals to genetic counseling and testing between Black women and white women with breast cancer. Based on the results of the survey, the investigators are launching a pilot study in which facilitators will be matched with patients of the same race to perform in-person genetic screens. WU Record 10/18/21 | J Clin Oncol 2021 Oct 18
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Most cases of never-smokers’ lung cancer treatable with mutation-targeting drugs
About 78-92% of lung cancers in patients who have never smoked can be treated with precision drugs already approved by the Food and Drug Administration to target specific mutations in a patient’s tumor. Siddhartha Devarakonda, Ramaswamy Govindan, and their colleagues found that most never-smokers’ lung tumors had so-called driver mutations, specific mistakes in the DNA that fuel tumor growth and that can be blocked with a variety of drugs. WU Record 9/30/21 | J Clin Oncol 2021 Sep 30
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Liquid biopsies may aid diagnosis, treatment of bladder, nerve tumors
Analysis of DNA in blood and urine (liquid biopsy) could lead to faster and less invasive methods to diagnose and monitor various types of tumors. Two studies co-authored by Vivek Arora and Angela Hirbe describe the potential of liquid biopsies to identify and track tumor growth in two very different cancers: bladder cancer and peripheral nerve sheath tumors. Both studies appear in the August 31 issue of PLOS Medicine, which is a special issue of the journal dedicated to liquid biopsies. WU Record 8/31/21 | Article 1 | Article 2
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Siteman Cancer Center plans for 9-story outpatient facility on Medical Campus
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is planning a new, nine-story facility on the Washington University Medical Campus dedicated solely to outpatient cancer care. The facility will provide a central home for nearly all aspects of advanced cancer care for outpatients, improving the experience and comfort for patients and their families. WU Record 7/30/21
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Cell-based immunotherapy shows promise against melanoma
An immunotherapy based on supercharging the immune system’s natural killer cells has been effective in treating patients with recurrent leukemia and other difficult to treat blood cancers. Now, a team led by Todd Fehniger has shown in preclinical studies conducted in mice and human cells that this type of cell-based immunotherapy also could be effective against solid tumors, starting with melanoma, a type of skin cancer that can be deadly if not caught early. WU Record 6/29/21 | Clin Cancer Res 2021 Jun 29
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Newly approved drug effective against lung cancer caused by genetic mutation
The new drug sotorasib reduces tumor size and shows promise in improving survival among patients with lung tumors caused by a specific DNA mutation in the KRAS gene, according to results of a global phase 2 clinical trial. The drug is designed to shut down the effects of the mutation, which is found in about 13% of patients with lung adenocarcinoma, a common type of non-small-cell lung cancer. WU Record 6/4/21 | NEJM 2021 Jun 4
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Stuart Kornfeld receives honorary degree from Washington University
Stuart Kornfeld is one of six people who received honorary degrees at Washington University's commencement on May 20-21. He is best known for the study of how sugars attach to proteins and the roles these molecules play in how cells function. His work on the trafficking of proteins to lysosomes via the mannose-6-phosphate pathway led to new understandings of inherited disorders known as lysosomal storage diseases. WU Record 5/5/21
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Zika virus helps destroy deadly brain cancer in mice
The Zika virus that ravaged the Americas, leaving many babies with permanent brain damage, may have a silver lining, according to a study published by Milan Chheda and colleagues. The virus can activate immune cells to destroy glioblastoma cancer cells in mice, giving a powerful boost to an immunotherapy drug (anti-PD-1 antibody) and sparking long-lasting immunological memory that can ward off tumor recurrence for at least 18 months. WU Record 3/24/21 | JCI Insight 2021 Jan 11
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Promising role for whole genome sequencing in guiding blood cancer treatment
A new study led by David Spencer suggests whole genome sequencing is a reliable and practical approach for detecting all of the changes that are important for assessing the risk of relapse for AML and MDS patients. This approach can be performed when conventional testing methods are unsuccessful and also could be applied to other cancers, including solid tumors. The cost of genome sequencing technology recently reached a level similar to that of conventional testing, and results can be returned to patients in just a few days WU Record 3/10/21 | NEJM 2021 Mar 11
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Aggressive brain tumor mapped in genetic, molecular detail
Glioblastoma is among the most aggressive and devastating of cancers. In a study led by Li Ding, members of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium performed high-resolution and high-depth analyses on 99 glioblastoma tumors. Harnessing new technologies, including proteomics, metabolomics and single cell sequencing, this study is an extremely deep dive into glioblastoma tumor biology, revealing new possibilities for therapy. WU Record 2/11/21 | Cancer Cell 2021 Feb 2
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Nixing bone cancer fuel supply offers new treatment approach
An innovative approach to treating bone tumors — starving cancer cells of the energy they need to grow — could one day provide an alternative to a commonly used chemotherapy drug without the risk of severe side effects. Studying human cancer cells and mice, Brian Van Tine and associates found that a two-drug combination targeting a tumor’s energy sources could be as effective and less toxic than methotrexate to treat osteosarcoma. WU Record 1/26/21 | Cell Reports 2021 Jan 26
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GI tract may be vulnerable to COVID-19 infection
Research published by Ramon Jin, a clinical fellow in the Division of Medical Oncology, and co-workers in Jason Mills's laboratory suggests that people with Barrett’s esophagus (a major risk factor for cancer of the esophagus) may be vulnerable to infection after swallowing the virus that causes COVID-19. They analyzed tissue from 30 patients with Barrett’s esophagus and found that cells in the tissue samples all had receptors for the SARS-CoV-2 virus, which normal esophagus cells lack. WU Record 1/20/21 | Gastroenterology 2021 Jan 20
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New discovery could help improve cancer vaccines
Jeff Ward and Chris Miller are members of a global consortium that has identified features of tumor neoantigens that trigger T cells to attack the cancer and leave healthy tissue untouched. They used computer modeling to accurately predict 75% of effective neoantigens and eliminate 98% of ineffective mutant proteins in melanoma and a common type of lung cancer. The results will help researchers design better immunotherapies against cancer. WU Record 10/9/20 | Cell 2020 Oct 2
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Siteman Cancer Center earns highest federal rating
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis has been recognized once again as a top U.S. cancer institution, based on a review of its research programs. This evaluation resulted in a nearly perfect score, earning Siteman the highest possible rating — exceptional — by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). WU Record 7/10/20
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Walter named Edward P. Evans Endowed Professor
Matthew J. Walter, MD, has been named the inaugural Edward P. Evans Endowed Professor at Washington University School of Medicine. Walter, an international leader in the study and treatment of myelodysplastic syndromes (MDS), a group of rare blood disorders that prevents the body from making sufficient healthy blood cells, is a professor of medicine and director of the Edward P. Evans Center for Myelodysplastic Syndromes at the School of Medicine. WU Record 1/17/20
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$3.7 million supports crowdsourced database of cancer genomics
Washington University has received a $3.7 million grant from the National Institutes of Health to support an open-source database aimed at boosting personalized approaches to cancer treatment. The database, called CIViC, was designed by computational biologists Obi Griffith and Malachi Griffith. Its purpose is to help doctors match cancer mutations found in patients’ tumors with drugs that target such genetic errors. WU Record 10/15/19
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Cause of rare, fatal disorder in young children pinpointed
Mark Sands and his colleagues have discovered the precise biochemical pathway leading to Krabbe disease, a fatal genetic disorder in children that results in seizures, developmental regression and death, usually around age 3. Studying a mouse model, they also identified a possible therapeutic strategy for this disease. WU Record 9/16/19 | PNAS 2019 Sep 16
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$5 million grant endows research on myelodysplastic syndrome
Washington University has received a $5 million grant to establish the Edward P. Evans Myelodysplastic Syndromes Center led by oncologist Matthew Walter. A major goal of the center is to launch a clinic that will follow healthy individuals with normal blood counts and mutations in key genes that are linked to MDS. By studying this group of patients, the investigators hope to understand the differences between those patients who go on to develop MDS and those who don’t. WU Record 9/11/19
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$15 million supports quest for personalized leukemia therapies
A team of Washington University investigators led by Tim Ley have been awarded a $15 million NIH grant to better understand the genetic changes that drive acute myeloid leukemia and predict patients’ responses to therapy. The findings may enable development of more effective therapies tailored to patients, based on the genetic characteristics of their cancer cells. WU Record 8/21/19
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Half-century of research illuminates how cells work in health, disease
More than 50 years ago, Stuart Kornfeld, was awarded his first research grant. That grant enabled him to set out on a field of study that would lay the foundation for understanding cells' behavior in health and inherited diseases. WU Record 7/30/19
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Fighting pancreatic cancer with immunotherapy
In collaboration with investigators at Rush University in Chicago, David DeNardo and colleagues have found a chemical compound that promotes a vigorous immune assault against pancreatic cancer in mice. Alone, the compound reduces pancreatic tumor growth and metastases. But when combined with immunotherapy, the compound significantly shrank tumors and dramatically improved survival in the animals. WU Record 7/3/19 | Science Translational Medicine 2019 Jul 3
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Tim Ley elected to National Academy of Sciences
Tim Ley led the team that first sequenced a cancer genome, identifying mutations in DNA that lead to cancer growth. His research has laid the groundwork for precision medicine in cancer treatment, which uses the genetic makeup of a patient’s tumor and how it responds to therapy as a guide for how best to attack that specific patient’s disease. WU Record 4/30/19
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$9 million supports deep dive into breast, pancreatic cancers
Washington University School of Medicine has received a $9 million grant from the National Institutes of Health to study the life histories of breast and pancreatic cancers. Led by Li Ding and colleagues in the Departments of Surgery and Radiology, the research will focus on how breast cancer evolves in response to treatments and how some tumors develop resistance to these treatments. A second project will focus on how pancreatic cancer spreads, or metastasizes, and develops resistance to standard treatments. WU Record 1/9/19
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$20 million gift from Paula C. and Rodger O. Riney boosts multiple myeloma research
Their gift establishes the Paula C. and Rodger O. Riney Blood Cancer Research Initiative Fund to develop promising new treatments for multiple myeloma. The work will be carried out by a research team of physicians and scientists at the Alvin J. Siteman Cancer Center and Washington University School of Medicine with broad expertise in multiple myeloma, genomics, immunology and immunotherapy, imaging and pharmacogenomics. WU Record 11/29/18
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$11.5 million supports innovation in leukemia research
Extending its standing as one of the top leukemia programs in the United States, Washington University School of Medicine has been awarded an $11.5 million grant to further high-level investigations into leukemia and related blood cancers. The grant, from the National Institutes of Health (NIH), funds a prestigious Specialized Program in Research Excellence (SPORE) in leukemia. The Washington University SPORE, led by Dan Link is one of only three academic centers in the U.S. to receive this grant. WU Record 11/6/18
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Relapsed leukemia flies under immune system's radar
A study led by Matthew Christopher, Allegra Petti, Michael Rettig and Timothy Ley offers a potential explanation for why many AML patients experience a relapse after a stem cell transplant and suggests a therapeutic approach that may help to place relapsed patients back into remission. The investigators found that leukemia cells from patients who relapsed after transplant often had greatly reduced expression of genes that were involved with the recognition of cancer cells by the immune system and that interferon gamma could restore expression of these genes. WU Record 10/31/18
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New clues found to understanding relapse in breast cancer
A large genomic analysis led by Obi Griffith in the Division of Oncology and The McDonnell Genome Institute has linked certain DNA mutations to a high risk of relapse in estrogen receptor positive breast cancer. The knowledge could help guide treatment decisions. Nature Communications 2018 Sep 4 | WU Record 9/14/18
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Analysis of prostate tumors reveals clues to cancer’s aggressiveness
Using genetic sequencing, scientists have revealed the complete DNA makeup of more than 100 aggressive prostate tumors, pinpointing important genetic errors these deadly tumors have in common. The study lays the foundation for finding new ways to treat prostate cancer, particularly for the most aggressive forms of the disease. The multicenter study was led by co-senior author Chris Maher of the Oncology Division and investigators at the University of California, San Francisco.
Cell 2018 Jul 19 | WU Record 7/19/18 -
$5 million supports innovative breast cancer trial
Ron Bose and Cynthia Ma have received a $5 million grant from the Department of Defense to support their research on HER2-positive breast cancer. The grant will fund a clinical trial of the HER2 inhibitor neratinib in combination with fulvestrant in patients with metastatic breast tumors that have HER2 mutations and are estrogen-receptor positive. To understand how patients respond to these drugs, the researchers will implant the patients’ tumors into mice that then will receive the same treatment regimen. Genome sequencing and protein analysis of the tumors will be performed to seek clues to how some of them develop drug resistance. WU Record 5/10/18
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Experimental arthritis drug prevents stem cell transplant complication
An investigational drug in clinical trials for rheumatoid arthritis prevents a common, life-threatening side effect of stem cell transplants, new research from Jaebok Choi, John DiPersio and colleagues. Studying mice, the researchers found the drug prevented graft-versus-host disease, a debilitating, sometimes lethal condition that develops when transplanted stem cells attack the body’s own organs or tissues. Leukemia 2018 Apr 2 | WU Record 4/24/18
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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. New England Journal of Medicine 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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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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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 | WU Record 1/5/16
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TGF-Beta Signaling in Myeloproliferative Neoplasms Contributes to Myelofibrosis Without Disrupting the Hematopoietic Niche
Yao JC, Oetjen KA, Wang T, Xu H, Abou-Ezzi G, Krambs JR, Uttarwar S, Duncavage EJ, Link DC
J Clin Invest 2022 Apr 19:e154092; [ahead of print]
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Structure of the Human GlcNAc-1-Phosphotransferase αβ Subunits Reveals Regulatory Mechanism for Lysosomal Enzyme Glycan Phosphorylation
Li H, Lee WS, Feng X, Bai L, Jennings BC, Liu L, Doray B, Canfield WM, Kornfeld S, Li H
Nat Struct Mol Biol 2022 Mar 24; [ahead of print]
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Antibody-Drug Conjugates Plus Janus Kinase Inhibitors Enable MHC-Mismatched Allogeneic Hematopoietic Stem Cell Transplantation
Persaud SP, Ritchey JK, Kim S, Lim S, Ruminski PG, Cooper ML, Rettig MP, Choi J, DiPersio JF
J Clin Invest 2021 Nov 2; [Epub ahead of print]
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U2af1 Is a Haplo-Essential Gene Required for Hematopoietic Cancer Cell Survival in Mice
Wadugu BA, Nonavinkere Srivatsan S, Heard A, Alberti MO, Ndonwi M, Liu J, Grieb S, Bradley J, Shao J, Ahmed T, Shirai CL, Khanna A, Fei DL, Miller CA, Graubert TA, Walter MJ
J Clin Invest 2021 Sep 21; [Epub ahead of print]
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Breast Cancer Derived GM-CSF Regulates Arginase 1 in Myeloid Cells to Promote an Immunosuppressive Microenvironment
Su X, Xu Y, Fox GC, Xiang J, Kwakwa KA, Davis JL, Belle JI, Lee WC, Wong WH, Fontana F, Hernandez-Aya L, Kobayashi T, Tomasson HM, Su J, Bakewell SJ, Stewart SA, Egbulefu C, Karmakar P, Meyer MA, Veis DJ, DeNardo DG, Lanza GM, Achilefu S, Weilbaecher KN
J Clin Invest 2021 Sep 14; [Epub ahead of print]
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KTE-X19 for Relapsed or Refractory Adult B-Cell Acute Lymphoblastic Leukaemia: Phase 2 Results of the Single-Arm, Open-Label, Multicentre ZUMA-3 Study
Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, Leguay T, Bishop MR, Topp MS, Tzachanis D, O'Dwyer KM, Arellano ML, Lin Y, Baer MR, Schiller GJ, Park JH, Subklewe M, Abedi M, Minnema MC, Wierda WG, DeAngelo DJ, Stiff P, Jeyakumar D, Feng C, Dong J, Shen T, Milletti F, Rossi JM, Vezan R, Masouleh BK, Houot R
Lancet 2021 Jun 3; [Epub ahead of print]
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Sotorasib for Lung Cancers With KRAS P.G12C Mutation
Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R
N Engl J Med 2021 Jun 4; [Epub ahead of print]
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Genome Sequencing as an Alternative to Cytogenetic Analysis in Myeloid Cancers
Duncavage EJ, Schroeder MC, O'Laughlin M, Wilson R, MacMillan S, Bohannon A, Kruchowski S, Garza J, Du F, Hughes AEO, Robinson J, Hughes E, Heath SE, Baty JD, Neidich J, Christopher MJ, Jacoby MA, Uy GL, Fulton RS, Miller CA, Payton JE, Link DC, Walter MJ, Westervelt P, DiPersio JF, Ley TJ, Spencer DH
N Engl J Med 2021 Mar 11;384(10):924-935
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Proteogenomic and Metabolomic Characterization of Human Glioblastoma
Wang LB, Karpova A, Gritsenko MA, Kyle JE, Cao S (co-first author), Li Y, Rykunov D, Colaprico A, Rothstein JH, Hong R, Stathias V, Cornwell M, Petralia F, Wu Y, Reva B, Krug K, Pugliese P, Kawaler E, Olsen LK, Liang WW, Song X, Dou Y, Wendl MC, Caravan W, Liu W, Cui Zhou D, Ji J, Tsai CF, Petyuk VA, Moon J, Ma W, Chu RK, Weitz KK, Moore RJ, Monroe ME, Zhao R, Yang X, Yoo S, Krek A, Demopoulos A, Zhu H, Wyczalkowski MA, McMichael JF, Henderson BL, Lindgren CM, Boekweg H, Lu S, Baral J, Yao L, Stratton KG, Bramer LM, Zink E, Couvillion SP, Bloodsworth KJ, Satpathy S, Sieh W, Boca SM, Schurer S, Chen F, Wiznerowicz M, Ketchum KA, Boja ES, Kinsinger CR, Robles AI, Hiltke T, Thiagarajan M, Nesvizhskii AI, Zhang B, Mani DR, Ceccarelli M, Chen XS, Cottingham SL, Li QK, Kim AH, Fenyo D, Ruggles KV, Rodriguez H, Mesri M, Payne SH, Resnick AC, Wang P, Smith RD, Iavarone A, Chheda MG, Barnholtz-Sloan JS, Rodland KD, Liu T, Ding L
Cancer Cell 2021 Feb 2;S1535-6108(21)00050-7
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Metabolic Compensation Activates Pro-Survival mTORC1 Signaling Upon 3-Phosphoglycerate Dehydrogenase Inhibition in Osteosarcoma
Rathore R, Caldwell KE, Schutt C, Brashears CB, Prudner BC, Ehrhardt WR, Leung CH, Lin H, Daw NC, Beird HC, Giles A, Wang WL, Lazar AJ, Chrisinger JSA, Livingston JA, Van Tine BA
Cell Rep 2021 Jan 26;34(4):108678
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TPL2 Enforces RAS-Induced Inflammatory Signaling and Is Activated by Point Mutations
Dodhiawala PB, Khurana N, Zhang D, Cheng Y, Li L, Wei Q, Seehra K, Jiang H, Grierson PM, Wang-Gillam A, Lim KH
J Clin Invest 2020 Jun 23; [Epub ahead of print]
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Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer
Hegde S, Krisnawan VE, Herzog BH, Zuo C, Breden MA, Knolhoff BL, Hogg GD, Tang JP, Baer JM, Mpoy C, Lee KB, Alexander KA, Rogers BE, Murphy KM, Hawkins WG, Fields RC, DeSelm CJ, Schwarz JK, DeNardo DG
Cancer Cell 2020 Mar 16;37(3):289-307e9
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Potently Cytotoxic Natural Killer Cells Initially Emerge From Erythro-Myeloid Progenitors During Mammalian Development
Dege C, Fegan KH, Creamer JP, Berrien-Elliott MM, Luff SA, Kim D, Wagner JA, Kingsley PD, McGrath KE, Fehniger TA, Palis J, Sturgeon CM
Dev Cell 2020 Apr 20;53(2):229-239e7
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Exploring the "Minimal" Structure of a Functional ADAMTS13 by Mutagenesis and Small-Angle X-Ray Scattering
Zhu J, Muia J, Gupta G, Westfield LA, Vanhoorelbeke K, Tolia NH, Sadler JE
Blood 2019 Apr 25;133(17):1909-1918
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Posttranscriptional Modulation of TERC by PAPD5 Inhibition Rescues Hematopoietic Development in Dyskeratosis Congenita
Fok WC, Shukla S, Vessoni AT, Brenner KA, Parker R, Sturgeon CM, Batista LFZ
Blood 2019 Feb 6; [Epub ahead of print]
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Mutation Clearance After Transplantation for Myelodysplastic Syndrome
Duncavage EJ, Jacoby MA, Chang GS, Miller CA, Edwin N, Shao J, Elliott K, Robinson J, Abel H, Fulton RS, Fronick CC, O'Laughlin M, Heath SE, Brendel K, Saba R, Wartman LD, Christopher MJ, Pusic I, Welch JS, Uy GL, Link DC, DiPersio JF, Westervelt P, Ley TJ, Trinkaus K, Graubert TA, Walter MJ
N Engl J Med 2018 Sep 13;379(11):1028-1041
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An "Off-The-Shelf" Fratricide-Resistant CAR-T for the Treatment of T Cell Hematologic Malignancies
Cooper ML, Choi J, Staser K, Ritchey JK, Devenport JM, Eckardt K, Rettig MP, Wang B, Eissenberg LG, Ghobadi A, Gehrs LN, Prior JL, Achilefu S, Miller CA, Fronick CC, O'Neal J, Gao F, Weinstock DM, Gutierrez A, Fulton RS, DiPersio JF
Leukemia 2018 Sep;32(9):1970-1983
2022 Hematology Retreat:
Program and Photos
Faculty Profile:
Alessandro Vindigni
