October 14, 2014 > 2014 NYSCF-Robertson Stem Cell Investigators named
Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) of the Broad Institute and Massachusetts Institute of Technology, Cambridge, is one of six promising early career scientists named as 2014 NYSCF-Robertson Stem Cell Investigators. The award is designed to support scientists engaged in novel neuroscience and cutting-edge translational stem cell research. Each Investigator will receive a generous five-year award.
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September 28, 2014 > Early sign of pancreatic cancer discovered
Matthew G. Vander Heiden, MD, PhD (Damon Runyon-Rachleff Innovator ‘11-‘13, Damon Runyon Fellow ‘06-‘08) of MIT, Cambridge, and colleagues, reported the discovery of a sign of the early development of pancreatic cancer – an increase in certain amino acids due to changes in metabolism. This occurs before the disease is diagnosed and symptoms appear, and the researchers hope that eventually they may be able to use this information to detect the disease earlier. These findings were published in the journal Nature Medicine.
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September 25, 2014 > New mouse model for genome editing and cancer modeling
Sidi Chen, PhD (Damon Runyon Fellow ‘12-‘15) and Feng Zhang, PhD (Damon Runyon-Rachleff Innovator ‘12-‘14) of the Broad Institute and Massachusetts Institute of Technology, Cambridge, developed a new mouse model that allows scientists to use the CRISPR-Cas9 system for in vivo genome editing experiments. They demonstrated the utility of the new “Cas9 mouse” model to edit multiple genes in a variety of cell types, and to model lung adenocarcinoma. The mouse has already been made available to the entire scientific community. These findings were published in the journal Cell.
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September 24, 2014 > Recruiting anthrax for drug delivery
Bradley L. Pentelute, PhD (Damon Runyon-Rachleff Innovator ’13-’15), and colleagues at Massachusetts Institute of Technology, Cambridge, used a disarmed version of the anthrax toxin to deliver two proteins known as antibody mimics, which can kill cancer cells by disrupting specific proteins inside the cells. In this study, they successfully targeted Bcr-Abl and hRaf-1, which both have known functions in cancer. This is the first demonstration of effective delivery of antibody mimics into cells, which could be applied to develop new drugs for cancer and other diseases. These findings were published in the journal ChemBioChem.
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September 8, 2014 > Splicing factor important for cancer development and metastasis
Zefeng Wang (Damon Runyon Fellow ’03-’06) of UNC School of Medicine, Chapel Hill, discovered that a protein crucial to the process of gene splicing, called RBM4, is drastically decreased in multiple forms of human cancer, including lung and breast cancers. This reduction in RBM4 results in altered gene expression, giving rise to cancer development and metastasis. Components of the splicing pathway could be potential targets for new cancer therapies. The study was published in the journal Cancer Cell.
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September 3, 2014 > Handheld scanner for accurate detection and removal of brain tumor cells
Moritz F. Kircher, MD, PhD (Damon Runyon-Rachleff Innovator ‘14-‘16) and colleagues at Memorial Sloan Kettering Cancer Center, New York, developed a new handheld device (“Raman scanner”) that can accurately detect cancer cells during surgery. The device resembles a laser pointer and detects nanoprobes that mark tumor cells but not normal cells. In a mouse model of glioblastoma, the scanner enabled researchers to successfully identify and remove all malignant cells in the animals’ brains. The device has the potential to move rapidly into clinical trials, eventually allowing surgeons to remove all cancer cells while sparing healthy tissue. This study was published in the journal ACS Nano.
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August 19, 2014 > 2014 Technology Review’s “35 Innovators under 35”
Emily P. Balskus, PhD (Damon Runyon-Rachleff Innovator ‘14-‘16) of Harvard University, Cambridge, has been named to MIT Technology Review’s list of “35 Innovators under 35” for her research focused on how gut bacteria use chemical reactions to survive. The list is comprised of “exceptionally talented technologists whose work has great potential to transform the world.”
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August 17, 2014 > Imaging how tumor cells transition to invasion
Ian Y. Wong, PhD (Damon Runyon Fellow ‘10-‘13) of Brown University, Providence, and colleagues, developed a microchip that enabled cancer cells to be imaged as they migrated across a surface that mimics the tissue surrounding a tumor. They examined cells that had undergone epithelial-mesenchymal transition (EMT), a process in which epithelial cells that stick together within a tissue, change into mesenchymal cells that can disperse and migrate individually. EMT is thought to play a role in cancer metastasis, allowing cancer cells to escape from tumor masses and colonize distant organs. This new imaging technology allows researchers to precisely measure how these cells move. Ultimately, they hope the device can be used for preliminary testing of drugs aimed at inhibiting cancer metastasis. This study was published in the journal Nature Materials.
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Improving and Expanding Our ProgramsAUGUST 2014
The Damon Runyon Cancer Research Foundation is committed to identifying and supporting exceptional early career researchers to accelerate progress against cancer. We pride ourselves on being an agile organization, able to rapidly target funding to where it can be most effective.
A recent assessment of our programs conducted by leading experts in the field of cancer research allowed us to ask if we could make a greater difference in finding cures for cancer faster. Based on the results of this rigorous review, we will be increasing our support for the nation’s best cancer researchers by 33%.
In a time of declining federal funding of research, we are stepping up to protect and encourage innovative cancer research in three major ways.
Strengthening the Damon Runyon Fellowship Award
“At a time when the entire funding universe is stepping back, [Damon Runyon is] moving forward.” – Leo D. Wang, MD, PhD, Damon Runyon-Sohn Fellow
Training More Physicians as Researchers
Supporting Daring Ideas
All together, we will be increasing our investment in innovative cancer research by 33% over the next 12 months.
These changes demonstrate our belief that continual assessment and expansion of our programs will ensure that the most brilliant scientists remain committed to groundbreaking cancer research.
August 1, 2014 > 2014 William B. Coley Award for Distinguished Research in Tumor Immunology
Gordon J. Freeman, PhD (Damon Runyon Fellow ‘79-‘81), of Harvard Medical School and Dana-Farber Cancer Institute, Boston, was named one of four recipients of the 2014 William B. Coley Award for Distinguished Research in Tumor Immunology. He is recognized for his contributions to the discovery of the programmed cell death-1 (PD-1) receptor pathway, a new immune system checkpoint that has been shown in clinical studies to be a highly promising target in cancer immunotherapy. PD-1 inhibitor drugs are effective in treating several types of deadly cancer, including melanoma, non-small cell lung cancer, head and neck cancer, bladder cancer, and kidney cancer.
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July 30, 2014 > Single cell sequencing of breast cancer genome
Nicholas E. Navin, PhD (Nadia’s Gift Foundation Damon Runyon-Rachleff Innovator ’13-’15) and colleagues at MD Anderson Cancer Center, Houston, developed a single cell sequencing tool (NUC-SEQ) that can measure genome-wide mutations in individual cancer cells. This study revealed that different subtypes of breast cancer have varied tumor diversity, and that different tumor cells grow at dramatically different speeds. These findings may have important implications for the diagnosis and treatment of breast cancer. This work was published in the journal Nature.
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New Discoveries eNewsletter: May - July 2014
Damon Runyon Foundation Grants Prestigious Fellowship Awards to 16 Top Young Scientists
Grants totaling over $3.3M give early career investigators independence to pursue novel ideas
New York, NY (July 14, 2014) – The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting innovative early career researchers, named 16 new Damon Runyon Fellows at its spring Fellowship Award Committee review. The recipients of this prestigious, four-year award are outstanding postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators across the country. The Fellowship encourages the nation’s most promising young scientists to pursue careers in cancer research by providing them with independent funding ($208,000 each for basic scientists, $248,000 for physician-scientists) to work on innovative projects.
May 2014 Damon Runyon Fellows:
Caitlin A. Brennan, PhD [Dennis and Marsha Dammerman Fellow], with her sponsor Wendy S. Garrett, MD, PhD, at the Harvard School of Public Health, Boston, studies colorectal cancer and its connection to the human microbiota- the collection of bacteria and other microbes associated with the body in both healthy and disease states. Her research will investigate how specific bacteria signal to both the immune system and other microbes in the development of colorectal cancer.
Dennis L. Buckley, PhD [Merck Fellow], with his sponsor James E. Bradner, MD, at the Dana-Farber Cancer Institute, Boston, aims to develop improved inhibitors of BET-bromodomain proteins for treatment of multiple cancers, such as NUT-midline carcinoma, acute leukemia, hematological malignancies and solid tumors. In addition, he will evaluate both novel and existing BET inhibitors in neuroblastoma. His goal is to chemically generate drugs with improved efficacy or lower side effects.
Casey A. Gifford, PhD [HHMI Fellow], with her sponsor Deepak Srivastava, MD, at the Gladstone Institutes, San Francisco, aims to define the roles for DNA-binding proteins that can manipulate DNA conformation in the nucleus. DNA is maintained in an ordered conformation that contributes to control of gene expression and cellular identity. She will employ next-generation sequencing approaches and human stem cells to better understand why the loss or aberrant expression of these DNA-binding proteins leads to cancer.
Keren I. Hilgendorf, PhD [Layton Family Fellow], with her sponsor Peter K. Jackson, PhD, at the Stanford University School of Medicine, Stanford, is exploring the role of primary cilia in regulating cell proliferation and differentiation. The primary cilium is an antenna-like cellular protrusion that is localized on the surface of most vertebrate cells and functions in chemo- and mechanosensation. In many cancers, primary cilia are lost, so cilia-mediated signaling pathways are deregulated.
Fuguo Jiang, PhD [Merck Fellow], with his sponsor Jennifer A. Doudna, PhD, at the University of California, Berkeley, is studying the CRISPR-Cas system, which has been adopted as a robust and versatile platform for genome engineering in human cells as well as other experimental systems. He aims to use a combination of biochemical and biophysical approaches to investigate the detailed molecular mechanism of RNA-guided DNA targeting and recognition by CRISPR-Cas9. The results of this research will provide a fundamental understanding of the Cas9 enzyme family and will support its use for gene therapies against cancers.
Avinash Khanna, PhD [Rebecca Ridley Kry Fellow], with his sponsor Matthew D. Shair, PhD, at Harvard University, Cambridge, studies a type of leukemia called mixed lineage leukemia (MLL), which often results in early relapse and a poor prognosis for the patient. Recently, it was found that inhibition of a protein called Mediator diminishes the ability of AML cancer cells to grow and proliferate. This research will use small molecules to elucidate the chemical biology of Mediator proteins.
Yin Liu, PhD [Layton Family Fellow], with her sponsor Mark A. Krasnow, MD, PhD, at Stanford University, Stanford, studies lung biology. The lung is innervated by diverse types of sensory neurons, collectively called pulmonary sensory neurons. These neurons detect a variety of physiological stimuli from the lung and inform the central nervous system about the state of the lung. Lung cancer, one of the most common cancers with a high rate of lethality, is associated with symptoms such as chronic cough, shortness of breath, and referred cranial facial pain. Her research will examine how pulmonary sensory neurons recognize and respond to lung tumors and mediate lung cancer-associated clinical symptoms.
Chao Lu, PhD [Kandarian Family Fellow], with his sponsor C. David Allis, PhD, at The Rockefeller University, New York, is studying histones, proteins that fold DNA into high-order structures, which is critical for proper gene expression. Mutations in histones are mutated in certain types of pediatric brain tumors and sarcomas, including a rare bone cancer called chondroblastoma. He aims to understand the biochemical and molecular mechanisms by which histone proteins function and how they are perturbed in tumor cells.
Timothy D. Martin, PhD [Marion Abbe Fellow], with his sponsor Stephen J. Elledge, PhD, at Brigham and Women’s Hospital, Boston, focuses on genomic instability, a hallmark of virtually all cancers that underlies the mutations and aneuploidy (incorrect chromosome number) changes that perturb oncogenes and tumor suppressor genes (TSGs). Patient tumor sequencing has unveiled common genomic alterations across different cancers. The goal of this project is to precisely recreate these genomic alterations and directly test how each contributes to oncogenesis.
Mandy M. Muller, PhD [HHMI Fellow], with her sponsor Britt Glaunsinger, PhD, at the University of California, Berkeley, is examining Kaposi’s sarcoma-associated herpesvirus (KSHV), a virus associated with lifelong infections. A healthy immune system keeps the virus in check; however, in immunocompromised individuals, KSHV is associated with a number of malignances, including Kaposi’s sarcoma (KS). KSHV dramatically manipulates the intracellular gene expression environment of its host cell. The defining characteristic is a near-global depletion of cytoplasmic mRNA called “host shutoff.” The goal of this research is to mechanistically delineate how the virus hijacks host factors to dampen gene expression in the cell.
Duy P. Nguyen, PhD [Connie and Bob Lurie Fellow], with his sponsor James A. Wells, PhD, at the University of California, San Francisco, is analyzing the bacterial enzyme Cas9, which has emerged to be a versatile tool to manipulate the genome. He aims to develop an efficient method for selective delivery to and activation of Cas9 in cancer cells. The developed methodology will hopefully set the foundation for rapidly creating genetic models to interrogate signaling pathways implicated in cancer and to investigate novel drug screening approaches that identify new drug targets for cancer treatment.
Neel H. Shah, PhD, with his sponsor John Kuriyan, PhD, at the University of California, Berkeley, aims to elucidate structural details of the signaling enzyme ZAP-70, found primarily in immune T cells. Expression of ZAP-70 in other immune cells, B cells, however, is associated with chronic lymphocytic leukemia. Furthermore, loss of ZAP-70 function causes severe combined immunodeficiency; an impaired immune system can increase a patient’s susceptibility to tumor development. His research on ZAP-70 structure and function will help lay the groundwork for the development of ZAP-70-specific therapeutics.
Hume Akahori Stroud, PhD [HHMI Fellow], with his sponsor Michael E. Greenberg, PhD, at Harvard Medical School, Boston, is examining the distinct role of MeCP2, a protein that binds methyl-CpG-DNA and regulates neuronal chromatin, which “packages” DNA. The proposed research has significant implications for causes and mechanisms of cancer, as dysregulation of DNA methylation and other chromatin modifications represent early oncogenic events in a wide range of human cancers.
Tony Yu-Chen Tsai, PhD, MD [Kenneth G. and Elaine A. Langone Fellow], with his sponsor Sean G. Megason, PhD, at Harvard Medical School, Boston, seeks to understand how the signaling pathway directed by the protein Sonic Hedgehog (Shh) regulates cell-cell adhesion molecules required for correct spatial organization of the neuro-epithelium. Abnormal Shh signaling is associated with several types of cancer, and aberrant regulation of cell-cell adhesion could lead to tumor metastasis. His findings may ultimately lead to understanding and prevention of metastasis in Shh-associated cancers.
Daniel E. Webster, PhD, with his sponsor Louis M. Staudt, MD, PhD, at the National Cancer Institute, Bethesda, studies Diffuse Large B Cell Lymphoma (DLBCL), an aggressive cancer that hijacks the normal molecular mechanisms acting in immune B cells to drive malignant growth. Many genes have been studied as oncogenes or tumor suppressors in DLBCL, but a class of long non-coding RNAs (lncRNAs) remains largely unexplored for its function in this cancer. LncRNAs, once thought to be non-functional products of junk DNA, are now known to play an essential role in many biological processes. This research will discover oncogenic or tumor suppressive lncRNAs in DLBCL to uncover potential targets for cancer diagnosis or therapy.
Sungwook Woo, PhD [HHMI Fellow], with his sponsor Peng Yin, PhD, at Harvard University, Cambridge, is using protein structures to illustrate the mechanisms of cancer-related processes. His research aims to overcome limitations of current techniques by using recent breakthroughs in “programmable DNA self-assembly” to develop protein framework structures. If successful, his efforts will provide a general tool for structural biology and in turn benefit the mechanistic studies and therapeutic development for cancer.
To accelerate breakthroughs, the Damon Runyon Cancer Research Foundation provides today’s best young scientists with funding to pursue innovative research. The Foundation has gained worldwide prominence in cancer research by identifying outstanding researchers and physician-scientists. Twelve scientists supported by the Foundation have received the Nobel Prize, and others are heads of cancer centers and leaders of renowned research programs. Each of its award programs is extremely competitive, with less than 10% of applications funded. Since its founding in 1946, Damon Runyon has invested nearly $275 million and funded more than 3,420 young scientists. This year, it will commit over $16 million in new awards to brilliant young investigators.
100% of all donations to the Foundation are used to support scientific research. Its administrative and fundraising costs are paid from its Damon Runyon Broadway Tickets Service and endowment.
For more information visit www.damonrunyon.org
July 9, 2014 > Comprehensive genomic analysis of lung cancer completed
Matthew L. Meyerson, MD, PhD (Damon Runyon Fellow ‘95-‘98) of Dana-Farber Cancer Institute and the Broad Institute, Cambridge, led a recent study by the NIH Cancer Genome Atlas project, which represents the most comprehensive genomic analysis of lung adenocarcinoma, a cancer that forms in the tissues near the outer parts of the lungs. Researchers identified 18 key mutations in an analysis of 230 patient lung tumors. This identified new potential drug targets and may also help physicians to determine which existing cancer treatments could be most effective in treating each individual patient. This study was published in the journal Nature.
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June 26, 2014 > New genetic tests recommended in patients with ALCL non-Hodgkin lymphoma
Andrew L. Feldman, MD (Damon Runyon Clinical Investigator ‘09-‘14), and colleagues at the Mayo Clinic, Rochester, reported that novel genetic tests can be used to determine the best treatment options for patients with anaplastic large-cell lymphoma (ALCL), a rare type of non-Hodgkin lymphoma. There are three subgroups of ALCL that have very different survival rates. These subgroups could not be differentiated by routine pathology but only with the aid of the genetic tests, which the researchers recommend giving to all patients with ALK-negative ALCL. Each patient’s treatment should then be tailored based on the subgroup of his/her disease. The study was published in the journal Blood.
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Damon Runyon Cancer Research Foundation Awards over $4M to 10 Top Young Clinical Investigators
Public release date: 23-June-2014
New York, NY (June 23, 2014) - The Damon Runyon Cancer Research Foundation named seven new Damon Runyon Clinical Investigators at its spring 2014 Clinical Investigator Award Committee review. 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.
The Foundation also awarded Continuation Grants to three Damon Runyon Clinical Investigators. Each award will provide an additional two years of funding totaling $300,000. The Continuation Grant is designed to support Clinical Investigators who are approaching the end of their original awards and need extra time and funding to complete a promising avenue of research or initiate/continue a clinical trial. This program is possible through the generous support of the William K. Bowes, Jr. Foundation, and Connie and Robert Lurie.
The Clinical Investigator Award program is specifically intended to help address the shortage of physicians capable of translating scientific discovery into new breakthroughs for cancer patients. In partnerships with industry sponsors and through its new Accelerating Cancer Cures initiative, the Damon Runyon Cancer Research Foundation has committed nearly $49 million to support the careers of 77 physician-scientists across the United States since 2000.
2014 Clinical Investigator Awardees
Arash Ash Alizadeh, MD, PhD
Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive lymphoma in adults. Unfortunately, current therapies typically fail in nearly half of these patients. Dr. Alizadeh proposes a novel treatment strategy for this disease: to characterize and isolate premalignant stem cells before they transform into cancer cells. He has found that expression of a single oncogene called BCL6 is capable of reprogramming these cells from normal cells to aggressive malignant cells. He aims to define the specific genetic alterations that can give rise to this cell reprogramming. This research will be important both for understanding cancer biology, as well as for developing more effective means for treatment of lymphoma patients.
Dr. Alizadeh works under the mentorship of Ronald Levy, MD, at the Stanford University School of Medicine, Stanford, California.
Joshua Brody, MD
Dr. Brody aims to develop a novel treatment approach for patients with advanced-stage lymphoma, by which the patient’s immune system is trained to recognize and eliminate his/her own cancer. This approach, an “in situ vaccine,” recruits and activates specific immune cells, dendritic cells (DC), at the location of the treated tumor—where they can then educate the rest of the immune system to recognize and eliminate tumors throughout the body. The first patients enrolled on this clinical trial have already shown the recruitment and activation of DC within the treated tumor as well as regressions of lymphoma at sites distant from the treated site. The in situ vaccine will initially be tested in patients with low-grade lymphoma, with the goal of quickly expanding to other tumor types including melanoma and head and neck cancer.
Dr. Brody works under the mentorship of Nina Bhardwaj, MD, PhD, and Miriam Merad, MD, PhD, at The Icahn School of Medicine at Mount Sinai Hospital, New York, New York.
Lihua Elizabeth Budde, MD, PhD [The Jake Wetchler Foundation for Innovative Pediatric Cancer Research Clinical Investigator]
Hematopoietic stem cell transplant is the preferred and only curative treatment for most patients with acute myeloid leukemia (AML); however, a significant percentage of patients will eventually relapse. A novel effective therapy option is therefore urgently needed. Dr. Budde is testing a new strategy that uses patients’ own immune T cells, which have been modified to specifically target and kill leukemia cells. She will direct a Phase 1 clinical trial using these modified immune T cells as therapeutics for patients with AML. She is also developing ways to enhance the potency of these modified immune cells in killing leukemia cells. This therapeutic approach has the potential to change the treatment paradigm and may significantly improve the cure rate for patients with leukemia.
Dr. Budde works under the mentorship of Stephen J. Forman, MD, FACP, at City of Hope, Duarte, California.
Alejandro Gutierrez, MD
It remains unclear why some patients’ tumors can be cured with chemotherapy, whereas other tumors that appear to be nearly identical are completely chemoresistant. Dr. Gutierrez focuses on this issue in a particularly high-risk subset of T-cell acute lymphoblastic leukemia, a disease that most commonly affects older children and young adults. His goals are to define the molecular basis of resistance to conventional chemotherapy in patients with this disease, and to leverage this knowledge to develop a therapeutic strategy to restore chemosensitivity. Ultimately, this could lead to significant improvements in clinical outcome for these patients.
Dr. Gutierrez works under the mentorship of Stuart H. Orkin, MD, and Anthony Letai, MD, PhD, at Boston Children’s Hospital, Boston, Massachusetts.
Peter S. Hammerman, MD, PhD
Despite the initial success of targeted therapies for cancer, these treatments have limited efficacy in most diseases. Recent studies have shown that the immune cells that infiltrate a tumor play an active role in dictating the response to therapy; specific new therapies can augment the ability of the immune system to fight a cancer in combination with conventional therapies. Dr. Hammerman is using lung cancer as a model to explore genome-scale approaches to dissect this complex relationship between the tumor and its immune microenvironment. The goal of this research is to better define the optimal types of therapy for lung cancer by combining drugs that target the genetic alterations found in the tumor with those aimed at enhancing the immune response to the cancer, and to translate these findings into clinical practice.
Dr. Hammerman works under the mentorship of Glenn Dranoff, MD, Stephen F. Hodi, MD, and Kwok-Kin Wong, MD, PhD, at Dana-Farber Cancer Institute, Boston, Massachusetts.
Luc G. Morris, MD
Head and neck cancer is a lethal malignancy that can arise in the mouth, throat, voice box, and related areas. These tumors are squamous cell cancers that are, in many cases, caused by tobacco use or human papillomavirus (HPV) infection. Head and neck cancers have many molecular similarities with squamous cell cancers of the lung and esophagus. Dr. Morris is studying several poorly-understood genes that have been recently observed to be frequently altered in head and neck cancer (as well as lung and esophageal cancer). He has found that several of these genes act as tumor suppressor genes and in their normal state, prevent tumor development. In this project, he will determine the effects of these various gene alterations on tumor growth, cancer cell survival, and the clinical prognosis of patients. This work will help to develop new ways of therapeutically targeting the pathways that promote the development of head and neck and other tobacco and HPV-associated squamous cell cancers.
Dr. Morris works under the mentorship of Timothy Chan, MD, PhD, and James A. Fagin, MD, at Memorial Sloan Kettering Cancer Center, New York, New York.
Stephen T. Oh, MD, PhD [Doris Duke-Damon Runyon Clinical Investigator]
Myeloproliferative neoplasms (MPNs) are a group of blood cancers in which a malignant cell population proliferates out of control. Myelofibrosis (MF) is one type of MPN in which the bone marrow becomes replaced by scar tissue, leading to progressive failure of normal blood cell functions and ultimately death, on average five years after initial diagnosis. MPNs, including MF, can evolve to secondary acute myeloid leukemia (sAML), which is almost invariably fatal. There is no reliable curative treatment currently available for MPNs or MF. Targeted inhibitors of a protein called JAK2 provide significant symptomatic benefit for MF patients. However, these treatments do not cure the disease, nor has it been shown that they can prevent or delay progression to sAML. Dr. Oh aims to investigate the cellular abnormalities that underlie these blood cancers. These studies have the potential to lead to the development of improved treatments for MPNs.
Dr. Oh works under the mentorship of Daniel Link, MD, at Washington University, St. Louis, Missouri.
2014 Clinical Investigator Continuation Grants
Marie Bleakley, MD [Richard Lumsden Foundation Investigator]
Bone marrow transplantation, or allogeneic hematopoietic stem cell transplant (HCT), is the only curative therapy for many patients with leukemia. Certain immune cells, called T cells, contained in the donor HCT graft can cause a “graft versus leukemia” (GVL) effect which eliminates leukemic cells. Unfortunately, there are also donor T cells in the HCT graft that can cause a condition called “graft versus host disease” (GVHD). GVHD is a life-threatening immune response that remains the major barrier to the success of transplantation. Dr. Bleakley is developing new approaches to separate the beneficial GVL effect from detrimental GVHD after bone marrow transplantation. She has identified specific subsets of immune cells that promote GVHD; these cells can then be eliminated to reduce the frequency or severity of GVHD, while at the same time maintaining and improving the GVL effect. The Continuation Grant will be used to move this study to the clinical trial phase.
Dr. Bleakley works under the mentorship of Stanley R. Riddell, MD, at the Fred Hutchinson Cancer Research Center, Seattle, Washington.
Zsofia K. Stadler, MD
Dr. Stadler is a clinical geneticist whose research goal is to determine the genetic basis of “sporadic” cancers in young adults. She is testing the hypothesis that de novo (spontaneous) chromosomal changes in the genome are associated with testicular germline cancer. The Continuation Grant will be used to apply high-resolution sequencing technology to compare the whole genomes of patients to those of their parents, with the goal of identifying rare genetic variants associated with cancer susceptibility and risk. This approach represents a new paradigm in cancer genetics, which could have broad applications in terms of cancer risk stratification and cancer prevention.
Dr. Stadler works under the mentorship of Kenneth Offit, MD, MPH, and Michael H. Wigler, PhD, at Memorial Sloan Kettering Cancer Center, New York, New York.
Jean Y. Tang, MD, PhD
Basal cell carcinoma (BCC) is the most common type of skin cancer. Mutations in the Hedgehog (HH) signaling pathway are frequently found in these cancers. Early-stage clinical studies of a HH pathway inhibitor drug have been successful, with 55% of patients reported to respond. However, most tumors develop drug resistance during the course of therapy. Dr. Tang has characterized mechanisms of drug resistance and is working to identify new drug combinations that are effective in treatment of BCC. The Continuation Grant will enable her to move her findings on resistance to clinical trials in patients. Her studies have the potential to benefit patients with BCC as well as those with other HH-dependent cancers, such as medulloblastoma.
Dr. Tang works under the mentorship of Philip A. Beachy, PhD, and Ervin H. Epstein, MD, at Stanford University, Stanford, California.
To accelerate breakthroughs, the Damon Runyon Cancer Research Foundation provides today’s best young scientists with funding to pursue innovative research. The Foundation has gained worldwide prominence in cancer research by identifying outstanding researchers and physician-scientists. Twelve scientists supported by the Foundation have received the Nobel Prize, seven others have received National Medals of Science, and 65 have been elected to the National Academy of Sciences. Since its founding in 1946, Damon Runyon has invested nearly $275 million and funded more than 3,420 young scientists.
100% of all donations to the Foundation are used to support cutting-edge scientific research. Its administrative and fundraising costs are paid from its Damon Runyon Broadway Tickets and endowment.
For more information visit www.damonrunyon.org.
Yung S. Lie, PhD
Chief Scientific Officer
Damon Runyon Cancer Research Foundation
Damon Runyon Cancer Research Foundation Awards $1.8 Million to 6 Innovative Early Career Scientists
Public release date: 14-January-2015
New York, NY (January 14, 2015) - The Damon Runyon Cancer Research Foundation announced that six scientists with novel approaches to fighting cancer have been named 2015 recipients of the Damon Runyon-Rachleff Innovation Award. The grant of $300,000 over two years is awarded each year to early career scientists whose projects have the potential to significantly impact the prevention, diagnosis and treatment of cancer. Each awardee will have the opportunity for up to two additional years of funding (up to four years total for $600,000). Continued support for years three and four will be granted to those awardees who demonstrate significant progress on their proposed research during the first two years of the award.
The Damon Runyon-Rachleff Innovation Award funds cancer research by exceptionally creative thinkers with “high-risk/high-reward” ideas who lack sufficient preliminary data to obtain traditional funding. The awardees are selected through a highly competitive and rigorous process by a scientific committee comprised of leading cancer researchers who are innovators themselves. Only those scientists with a clear vision and passion for curing cancer are selected to receive the prestigious award. This program was established thanks to the generosity of Andy and Debbie Rachleff.
2015 Damon Runyon-Rachleff Innovators:
Nicholas T. Ingolia, PhD, University of California, Berkeley
The uncontrolled growth and metastasis of cancer cells is driven by changes in the genes expressed by these cells, relative to cells in healthy tissue. Understanding these gene expression changes provides key insights into the behaviors of cancer cells and guides the design of anti-cancer therapies. Dr. Ingolia is studying a cellular process called translation, which generates protein from RNA. Important gene expression changes result from differences in the translation of mRNAs into functional proteins, rather than the abundance of these mRNAs in the cell. He has developed innovative techniques to comprehensively profile translation in cells and proposes to apply this approach to understand the gene expression differences between normal and cancerous cells. These gene expression changes will reveal distinctive features of cancer cells that explain their pathological behavior and potentially expose new vulnerabilities of these cells that could be targeted to treat cancer.
Christopher M. Jewell, PhD, University of Maryland, College Park
Tumors evade the immune system by suppressing the function of T cells otherwise capable of destroying cancer cells. These T cells develop in lymph nodes - specialized tissues that control responses against cancer, infection, and other disease. As T cells become activated against tumors, the cells differentiate and proliferate at much slower rates. This decreased proliferation dramatically reduces the effectiveness of anti-tumor immune responses. Dr. Jewell is uniquely trained in both immunology and materials science. He is harnessing bioengineering, immunology, and polymer design to create degradable vaccine “depots” in lymph nodes. The goal is to use these depots to control how T cells develop, promoting a cell fate specific for attacking tumors that also maintains the ability to proliferate at the extremely high rates needed to clear existing tumors and protect against regrowth. This is the first time these ideas have been explored, and the findings from his research will support development of a new class of cancer vaccines that could clear existing tumors and prevent relapse.
Ning Jenny Jiang, PhD, University of Texas, Austin
Many diseases could be cured if the power of our own immune systems could be harnessed. For cancer, the theory of “cancer immunoediting” provides a hypothesis for how tumors escape detection by the immune system. Dr. Jiang, a biomedical engineer, works at the interface of systems biology, genomics, and immunology. Her lab is developing a single cell-based integrated technological approach to challenge this theory. She will profile the immune system repertoire for antigen specificity, receptor gene sequences, and cellular function-related gene expression. Her approach may provide explanations for why and how the immune system tolerates tumors. Her proposed study may result in a paradigm shift that could improve cancer immunotherapies and also revolutionize health care with new personalized immune metrics for early disease detection and targeted therapy.
Guillem Pratx, PhD, Stanford University, Stanford
Many studies have shown that the cancer cells within a tumor form a remarkably diverse population. These cellular differences play a significant role in how the tumor develops and how it responds to therapy. A technology called flow cytometry (a high-throughput method for characterizing single cells) has been critical for these findings; however, the technology is inherently limited because it can only measure biochemical processes that can be interrogated using a fluorescent molecule. Dr. Pratx, an engineer by training, is developing a novel method that would enable flow cytometry to measure single cell uptake of any non-fluorescent molecule. This challenging feat will be accomplished by exploiting the fact that molecules can be labeled by radioisotopes. This new tool could transform the ability to study normal and abnormal molecular processes in single cancer cells by allowing flow cytometry to interrogate a much wider range of biomolecules, with high throughput and high temporal resolution.
Brian H. Shirts, MD, PhD, University of Washington, Seattle
Clinical testing for inherited cancer risk often leads to identification of rare genetic variants, but it is uncertain if these variants affect cancer risk. This uncertainty is difficult for cancer patients who want to know the best way to prevent future cancers in themselves and their families. Dr. Shirts is a clinical geneticist whose goal is to empower patients who have been diagnosed with rare genetic mutations (variants of uncertain significance, or VUS) to actively participate in family tree pedigree building to understand their own genetic risk for cancer and other diseases. He will develop an online toolkit to help cancer patients use publicly available genealogy and networking resources to determine if their own variants travel with cancer in their extended family. This project will pioneer an efficient way for patients and their families to work with genetics laboratories to classify VUS, giving cancer patients control over their own genetic information. This innovative strategy will also create a new source for the highest quality genotype-cancer correlation data, which will benefit cancer researchers and, eventually, everyone at risk for cancer.
Elçin Ünal, PhD, University of California, Berkeley
Aging is the primary risk factor for developing cancer. Despite the growing list of age-associated defects, we do not yet understand why aging is one of the most potent carcinogens. Dr. Ünal proposes to study a natural developmental process, called gametogenesis, which reverses cellular aging. She will use this as a platform to illuminate the molecular causes of aging and to develop new strategies to counteract age-induced cellular damage. Her approach will identify the genes that play a direct role in attenuating the aging process and could facilitate the development of novel strategies to improve human health by decreasing susceptibility to cancer.
To accelerate breakthroughs, the Damon Runyon Cancer Research Foundation provides today’s best young scientists with funding to pursue innovative research. The Foundation has gained worldwide prominence in cancer research by identifying outstanding researchers and physician-scientists. Twelve scientists supported by the Foundation have received the Nobel Prize, and others are heads of cancer centers and leaders of renowned research programs. Each of its award programs is extremely competitive, with less than 10% of applications funded. Since its founding in 1946, the Foundation has invested over $287 million and funded more than 3,460 young scientists. This year, it will commit approximately $15 million in new awards to brilliant young investigators.
100% of all donations to the Foundation are used to support scientific research. Its administrative and fundraising costs are paid from its Damon Runyon Broadway Tickets Service and endowment. For more information visit http://www.damonrunyon.org
For more information visit www.damonrunyon.org.
Yung S. Lie, PhD
Chief Scientific Officer
Damon Runyon Cancer Research Foundation
Damon Runyon, Sohn Conference Foundations Name 3 New Pediatric Cancer Research Fellows
New York, Memphis, Boston scientists receive prestigious awards to tackle cancers in children and young adults
New York, NY (June 20, 2014) – The Damon Runyon Cancer Research Foundation has named three outstanding young scientists as recipients of the prestigious Damon Runyon-Sohn Pediatric Cancer Research Fellowship Award, committing nearly $625,000 to help address a critical shortage of funding for pediatric cancer research.
The Fellowship Award provides funding to basic scientists and clinicians who conduct research with the potential to significantly impact the prevention, diagnosis or treatment of one or more pediatric cancers. Each recipient receives a four-year award ($248,000 for physician-scientists, $208,000 for basic scientists). Since 2012, this award has supported ten innovative pediatric cancer researchers.
The Sohn Conference Foundation, dedicated to curing pediatric cancers, announced in 2012 that it was granting $1.5 million to the Damon Runyon Cancer Research Foundation, the leading charity supporting innovative young cancer researchers, to establish the award. With the generous support of the Pershing Square Sohn Cancer Research Alliance, the Fellowship Award continues to receive funding and recognition within the philanthropic community.
2014 Damon Runyon-Sohn Fellows
Ly P. Vu, PhD, with her sponsors Michael Kharas, PhD, and Ross L. Levine, MD, at Memorial Sloan Kettering Cancer Center, New York, New York, is studying childhood acute myeloid leukemia (AML). Despite exciting advances in our understanding of AML and the availability of more aggressive treatment regimens, approximately 30% of children still eventually relapse from this disease. There are yet no approved targeted therapies for children with AML. Her project aims to uncover the role of Syncrip, a novel RNA binding protein, in maintaining the leukemia stem cell in AML. The study will provide insights into the mechanisms underlying the cause and development of AML and may lead to innovative therapeutic strategies and improved clinical outcomes for this deadly childhood disease.
David W. Woessner, PhD, with his sponsor Charles G. Mullighan, MBBS, MD, at St. Jude Children’s Research Hospital, Memphis, Tennessee, seeks to identify genetic changes that cause the most common type of childhood cancer, acute lymphoblastic leukemia (ALL). There are multiple subtypes of ALL, each with distinct genetic changes that drive disease development and influence success or failure of treatment. He has sequenced the genomes of over 1000 tumor cells from children with ALL and identified several hundred repeatedly mutated genes, for which the functions are currently unknown. He will test the role of these changes in ALL. A better understanding of which genetic changes significantly impact cancer behavior in ALL will provide new targets for existing therapy and/or avenues for development of new drug treatments for children with ALL.
Mark W. Zimmerman, PhD, with his sponsor A. Thomas Look, MD, at the Dana-Farber Cancer Institute, Boston, Massachusetts, studies neuroblastoma, a type of brain tumor that remains a challenging and often devastating condition despite many recent advances in its clinical management. In high-risk neuroblastoma tumors, which account for 15% of all childhood cancer deaths, the CHD5 gene is often deleted and its loss is associated with poor prognosis. CHD5 has emerged as a very attractive target for potential anti-cancer therapeutics. His research elucidating the CHD5 pathway will lead to significant advances in our understanding of how CHD5 functions as a tumor suppressor and the potential ways it could be targeted for anti-cancer therapy.
“These are some of the best young scientists working in pediatric research today, and they’re at a critical juncture in their careers,” says William Carroll, MD, chair of the Damon Runyon-Sohn Pediatric Cancer Fellowship Committee and Director of the New York University Cancer Institute. “They need our financial support, and we need their brilliant minds focused on curing childhood cancers. That is why this award is so important.”
Because cancer occurs less frequently in children and young adults than in the adult population, it does not receive significant funding from either the National Cancer Institute (only four percent of its budget) or the biopharmaceutical industry. As a result, there have been limited advances in recent years in treating these cancers, and fewer scientists are working in this field.
“I am inspired by Damon Runyon’s dedication to supporting excellent young scientists who are dedicating themselves to cancer research,” says Evan Sohn of the Sohn Conference Foundation. “Our Foundation is investing in this unique fellowship because it has the potential to change how cancer care is provided to children and young adults.”
The Foundation was established in memory of Ira Sohn, a Wall Street professional whose life was cut short when he passed away from cancer. For more than fifteen years, the Foundation has raised funds for pediatric cancer research through its highly respected annual investment conference, the Sohn Investment Conference, which features many of Wall Street’s best and most successful investors. Thanks to the dedication of the conference founders, esteemed speakers, volunteers, and generous donors, the Foundation has invested more than $20 million in innovative research and institutions at the forefront of cancer research and pediatric care.
The Pershing Square Sohn Cancer Research Alliance was formed in October 2013 by The Pershing Square Foundation and The Sohn Conference Foundation and is dedicated to playing a catalytic role in accelerating cures for cancer by enabling the pursuit of the most innovative and advanced cancer research and by facilitating partnerships between science and business.
To accelerate breakthroughs, the Damon Runyon Cancer Research Foundation provides today’s best young scientists with funding to pursue innovative research. Twelve scientists supported by the Foundation have received the Nobel Prize, seven have received National Medals of Science, and 65 have been elected to the National Academy of Sciences, the science “Hall of Fame.”
Since its founding in 1946, Damon Runyon has invested nearly $275 million and funded more than 3,420 young scientists. 100% of all donations to the Foundation are used to support cutting-edge scientific research. Its administrative and fundraising costs are paid from Damon Runyon Broadway Tickets and its endowment.
For more information, visit http://www.damonrunyon.org.
Yung S. Lie, PhD
Deputy Director and Chief Scientific Officer
Damon Runyon Cancer Research Foundation
The Sohn Conference Foundation
Pershing Square Sohn Cancer Research Alliance
2014 Annual Breakfast Honoring Steven Kandarian Raises $1.6 Million
New York, NY (June 5, 2014) The Damon Runyon Cancer Research Foundation honored Steven A. Kandarian, CEO of MetLife and Damon Runyon Board of Directors member, at its 2014 Annual Breakfast, held on Tuesday morning at Cipriani 42nd Street in New York City. The Breakfast raised more than $1.6 million to support the nation’s most brilliant young cancer researchers, pursuing work that promises to accelerate cures.
Alan M. Leventhal, Chairman of the Damon Runyon Board, welcomed guests to a program that included research updates from Himisha Beltran, MD, a Damon Runyon -Gordon Family Clinical Investigator at Weill Cornell Medical College pursuing personalized treatments for drug-resistant prostate cancer, and Adam de la Zerda, PhD, a Damon Runyon-Dale F. Frey Scientist at Stanford University working on improved imaging techniques to detect and destroy individual cancer cells.
The event’s keynote speaker was James E. Rothman, PhD, recipient of the 2013 Nobel Prize in Physiology or Medicine for work he began as a Damon Runyon Fellow from 1976 to 1978. Dr. Rothman reflected on how the early days of his career set a course for later success, noting “Damon Runyon was there for me when I wanted to take risks…I was trying to take on a major problem most people felt couldn’t be addressed.”
Dr. Rothman went on to praise the Foundation’s approach to cancer research, saying “By illuminating a broader swath of biology, researchers can have an unexpected impact. Some of the biggest discoveries are made this way.”
The morning’s honoree, Steven A. Kandarian, was introduced by Bruce E. Mosler, CEO of Cushman & Wakefield and Kandarian’s longtime friend. Damon Runyon Board of Directors member Sanford W. Morhouse, Esq. announced that Chao Lu, PhD, would be named the first Damon Runyon-Kandarian Family Fellow in recognition of Kandarian’s numerous contributions to Damon Runyon’s mission.
The Breakfast concluded with remarks from Kandarian, who spoke about cancer’s impact on his own family and his motivations for joining the Damon Runyon Board. “I was stunned by the swift and terrible power of cancer,” Kandarian said of the disease’s impact on his own family. “I can think of no better target for the intellectual energies of our most creative young researchers than this disease.”
DAMON RUNYON CANCER RESEARCH FOUNDATION
To accelerate breakthroughs, the Damon Runyon Cancer Research Foundation provides today’s best young scientists with funding to pursue innovative research. The Foundation has gained worldwide prominence in cancer research by identifying outstanding researchers and physician-scientists. Twelve scientists supported by the Foundation have received the Nobel Prize, seven others have received National Medals of Science, and 65 have been elected to the National Academy of Sciences.
Since its founding in 1946, Damon Runyon has invested nearly $275 million and funded more than 3,420 young scientists. One hundred percent of all donations to the Foundation are used to support cutting-edge scientific research. Its administrative and fundraising costs are paid from its Damon Runyon Broadway Tickets and endowment.
Damon Runyon Cancer Research Foundation
June 2, 2014 > Immunotherapy extends long-term survival of melanoma patients
Jedd D. Wolchok, MD, PhD (Damon Runyon-Lilly Clinical Investigator ‘03-‘08) at Memorial Sloan Kettering Cancer Center, New York, and colleagues, reported the results of an ongoing clinical trial evaluating the safety and activity of combined immunotherapies for treatment of advanced melanoma. Nivolumab (anti-PD-1), an investigational PD-1 immune checkpoint inhibitor, and ipilimumab (anti-CTLA-4; Yervoy), were given either concurrently or sequentially to these patients. The two-year overall survival rate was 88%. Only several years ago, the two-year survival rate for metastatic melanoma may have been less than 10 percent. These results were reported at the annual meeting of the American Society of Clinical Oncology and featured in The New York Times.