New York, NY (Jan. 12, 2017) - 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 fall 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 ($231,000 total) to work on innovative projects.
The Committee also named three new recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists. This award provides additional funding to scientists completing a prestigious Damon Runyon Fellowship Award who have greatly exceeded the Foundation's highest expectations and are most likely to make paradigm-shifting breakthroughs that transform the way we prevent, diagnose and treat cancer. Each awardee will receive $100,000 to be used toward their research.
Recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists:
Lydia Finley, PhD (Damon Runyon Jack Sorrell Fellow '13-'17)
Memorial Sloan Kettering Cancer Center, New York
Cancer cells frequently rewire intracellular metabolic pathways in order to support rapid proliferation. In addition to serving as building blocks for cell growth, metabolites also serve as critical substrates for enzymes that control gene expression programs. Changes in intracellular metabolites can therefore have a profound effect on cellular functions including survival, growth and differentiation. Dr. Finley found that specific intracellular metabolites promote the self-renewal of embryonic stem cells and thus can influence gene expression programs and control cell identity. She will continue to investigate how metabolites regulate cell fate decisions in stem cells and cancer cells. She will interrogate how cells rewire metabolic pathways to support growth and how these metabolic changes influence cellular programs that control self-renewal and differentiation. These studies will shed light on how cancer cells fuel their growth and how tumor-associated metabolic alterations contribute to the establishment of the stem cell-like state that characterizes the most malignant tumors.
Jens C. Schmidt, PhD (Damon Runyon-Merck Fellow '13-'15)
University of Colorado, Boulder
The telomerase enzyme adds repetitive DNA sequences to the ends of human chromosomes, assuring genome integrity and providing unlimited proliferative potential to continuously dividing cells. Importantly, 90% of all cancers require telomerase activity for their survival. Mutations that activate the expression of telomerase reverse transcriptase (TERT), the major protein subunit of telomerase, are the most frequent mutations in a number cancers and are strongly correlated with poor clinical outcomes for patients carrying them. Telomerase is therefore an attractive target to potentially treat a wide range of aggressive cancers. Dr. Schmidt has developed techniques to study telomerase trafficking in vivo, as well as single-molecule assays to analyze telomerase catalysis and its modulation in vitro. He is able to visualize enzymatic action of telomerase in real-time at nucleotide resolution. He aims to understand the enzymatic mechanism of telomerase catalysis to identify potential weaknesses that can be targeted to inhibit telomerase action in cancer cells.
Jakob von Moltke, PhD (Damon Runyon HHMI Fellow '13-'16)
University of Washington, Seattle
Immunotherapies that take the brakes off the immune response and direct cytotoxic T lymphocytes (CTLs) to hunt down tumors have revolutionized cancer treatment in the last decade. Stories of patients who are cured by immunotherapy even after exhausting all other treatment options are increasingly common -- but unfortunately, only a minority of patients achieve such remarkable benefits. Now, two pressing challenges are to understand why immunotherapy fails in non-responders and to develop new or modified therapies that achieve durable remission for these patients as well. Successful immunotherapy is predicated on the infiltration of the tumor microenvironment by tumor-specific CTLs. The cells and signals that generate and sustain these cells are collectively known as type 1 immunity. Conversely, the immune cells and signals associated with the distinct processes of tissue remodeling and wound healing are known as type 2 immunity. There is also evidence that the type 2 response may actually promote tumor growth and survival, so the success of cancer immunotherapy may therefore rely in part on preventing type 2 responses. Dr. von Moltke aims to understand the regulation of type 2 immune responses, with a particular focus on the earliest events that lead to initiation of type 2 immunity. He hopes that insights gained from these studies will inform the development of improved cancer immunotherapies that guide immune responses away from type 2 towards type 1.
November 2016 Damon Runyon Fellows:
Richard W. Baker, PhD, with his sponsor Andres Leschziner, PhD, at the University of California, San Diego, seeks to understand the molecular mechanism of how large protein assemblies actively rearrange local areas of chromatin, acting as keystone regulators of gene expression. He focuses on the SWI/SNF family of proteins. Recent genomic studies have shown that nearly 20% of all tumors contain a mutation in SWI/SNF genes. Notably, these mutations frequently result in with aberrant or uncontrolled SWI/SNF activity, suggesting that they could be viable drug targets. He is utilizing novel microscopy techniques to probe the mechanism of SWI/SNF-mediated chromatin remodeling and determine the effects of oncogenic mutations on this reaction. Understanding their mechanism of action is a key step towards developing new therapeutics.
Vladislav Belyy, PhD, with his sponsor Peter Walter, PhD, at the University of California, San Francisco, studies how cancerous cells bypass normal signaling pathways and continue to grow uncontrollably, instead of either repairing themselves or dying in response to "unfolded protein stress." Under these conditions, normal cells have evolved to sense this type of stress and either fix the problem or, if the fix fails, die in a controlled manner to protect the rest of the organism. He plans to use recent advances in light-activated protein engineering to study unfolded protein-mediated cell death and hopefully understand how cancerous cells are able to escape their programmed fate. These studies will potentially inform the next generation of cancer therapies targeting molecules involved in responding to the buildup of unfolded proteins.
Daniel J. Blair, PhD, with his sponsor -Martin D. Burke, MD, PhD-, at the University of Illinois, Urbana-Champaign, aims to address a key bottleneck in drug discovery by developing a generalizable strategy for synthesis of complex natural products to be used as therapeutics. Small molecules created by nature (natural products) often possess extraordinary functional potential and have led to many transformative human medicines. Unfortunately, despite important progress in the field of natural product synthesis, the methods available for synthesizing such complex natural products are typically too slow for practical drug discovery and development. He proposes to break down complex natural products into simple building blocks, which can then be iteratively assembled through automation to generate natural products.
Antony J. Burton, PhD, with his sponsor Tom W. Muir, at Princeton University, Princeton, studies how chemical modification of histone proteins leads to changes in the structure of chromatin, the physiologically relevant form of DNA, and how misregulation of this higher-order assembly can lead to aberrant gene transcription patterns and cancer. He will use chemical biology tools to carry out precise chemistry in live cells, and determine direct causality in the downstream effects on DNA accessibility and transcription.
Jeeyun Chung, PhD, with her sponsors Tobias C. Walther, PhD, and Robert V. Farese Jr., MD, at Harvard T.H. Chan School of Public Health, Boston, is focusing on the biology of fat storage organelles called lipid droplets (LDs). Many cancer cells are characterized by an increased number of LDs, and this accumulation has been proposed to be pathogenic. Key questions of LD biology remain unanswered, limiting the potential for therapeutic intervention. She will combine various imaging technologies and biochemical approaches to elucidate the molecular architecture of initial LD formation and its regulation.
Xintong Dong, PhD [HHMI Fellow], with her sponsor Xinzhong Dong, PhD, at Johns Hopkins University, Baltimore, studies how injury and pathogen invasion trigger a chain of inflammatory and repair responses that restore the damaged tissue. Defects in wound repair result in painful, non-healing ulcers that frequently affect aged individuals and diabetes patients. Malignant tumors are particularly severe complications, which often occur at sites of repetitive irritation and chronic wounds. She is investigating the roles of anti-microbial peptides during inflammation and wound healing, and hopes that these studies will provide insights about the cause and prevention of various carcinomas.
Ryan A. Flynn, MD, PhD, with his sponsor Carolyn R. Bertozzi, PhD, at Stanford University, Stanford, aims to understand the interplay between cancer metabolism and RNA biology at the level of protein modifications, such as glycosylation. The use of metabolites to fuel cellular processes including cell division and protein synthesis are critical in both healthy tissue and cancer growth. This work will define glycosylation events that respond to and regulate the cancer state within RNA-based networks, thereby establishing new layers of regulation for future therapeutic targeting.
Leeat Y. Keren, PhD, with her sponsors Michael R. Angelo, MD, PhD, and Edgar G. Engleman, MD, at Stanford University, Stanford, studies cellular changes in breast cancer, the second leading cause of cancer death in women in the U.S. Recently, a new multiplexed ion beam imaging (MIBI) technology has been introduced, which enables simultaneous imaging of dozens of proteins at a single cell level within a tissue section with high sensitivity. She is applying MIBI to study expression patterns of human breast cancer samples in the spatial context of the microenvironment and the interactions with the immune system. She aims to discover novel phenotypic and histologic features that predict progression from contained lesions to invasive disease.
Nora Kory, PhD [HHMI Fellow], with her sponsor David M. Sabatini, MD, PhD, at the Whitehead Institute of Biomedical Research, Cambridge, focuses on cancer cell metabolism. Cancer cells are characterized by rapid and uncontrolled cell growth. To sustain their accelerated growth, cancer cells rely on a constant supply of building blocks produced by specific metabolic pathways. One metabolic pathway, the mitochondrial one-carbon pathway, has recently been found to be especially important for the growth and survival of tumors and correlates with the survival of cancer patients. Inhibiting this pathway is a promising new strategy to treat cancer; however, its key components are still unknown. She aims to identify these components using a genetic screen applying the gene-editing CRISPR-Cas9 system to identify all genes required for its function in human cancer cells. She hopes to elucidate how cancer cells alter their metabolism to meet their high demands for building blocks and energy, which may also lead to the development of new drugs to treat cancers.
Lindsay LaFave, PhD, with her sponsor Tyler Jacks, PhD, at Massachusetts Institute of Technology, Cambridge, is studying how mutations in the SWI/SNF chromatin remodeling complex affect the initiation and progression of non-small cell lung cancer (NSCLC). Mutations in several SWI/SNF components have been identified in a variety of solid tumors; however, it remains unclear how their disruption contributes to tumor progression. She aims to develop novel NSCLC cell line and murine models to study the impact of SWI/SNF alterations. She will map the chromatin landscape in these models in order to characterize epigenetic changes that contribute to altered gene expression. These studies will lead to a greater understanding of SWI/SNF biology, potentially identifying novel therapeutic approaches for NSCLC patients.
Kara L. McKinley, PhD, with her sponsor Ronald D. Vale, PhD, at the University of California, San Francisco, studies how cells change their shape and behavior to build the complex structures that comprise mammalian organs. Cellular behaviors that occur during embryonic development are frequently co-opted by cancer cells during tumorigenesis and metastasis. Her goal is to understand how the machinery within cells drives changes in tissue architecture in a developmental context, generating new insights into how these cellular processes are corrupted during cancer progression.
Sarah J. Pfau, PhD, with her sponsor Chenghua Gu, PhD, at Harvard Medical School, Boston, aims to identify the molecular regulators of blood-brain barrier heterogeneity. The blood-brain barrier (BBB) protects the brain from harmful substances to ensure proper brain function. Consequently, the BBB renders many cancer therapeutics ineffective for treatment of primary and metastatic brain tumors, as drugs that effectively treat cancer in the rest of the body cannot efficiently enter the brain. She seeks to better understand how the BBB functions by characterizing the "windows of the brain," regions where the barrier is naturally more open to allow communication between the brain and the rest of the body through the bloodstream. In determining how the BBB is altered in these regions, she anticipates that her work will identify key molecular regulators that the brain naturally uses to open the blood-brain barrier and thus provide insight into how it can be modulated to promote drug delivery to tumors in the brain.
Jianjin Shi, PhD, with his sponsors Marc Tessier-Lavigne, PhD, and Ben A. Barres, MD, PhD, at Stanford University, Stanford, is exploring how cells die in the nervous system in both healthy and disease states. He will focus on a novel and ill-defined form of cell death in the nerve cells and nerve fibers upon injury or stress. Resisting cell death is a hallmark of all cancers. Furthermore, many cancer chemotherapeutic drugs cause the death of nerve cells and nerve fibers, therefore inducing neurological diseases in cancer patients. Using multiple state-of-the-art approaches, he aims to find the unknown components and molecular mechanisms of this type of cell death which will not only identify new drug targets for cancer treatments, but also shed light on how to reduce some side effects of chemotherapy.
Kurt J. Warnhoff, PhD, with his sponsor Gary B. Ruvkun, PhD, at Massachusetts General Hospital, Boston, is studying how the timing of developmental events is regulated at the genetic level. Importantly, failures in normal developmental biology often give rise to cancer. microRNAs (miRNAs) are a class of key regulators of developmental timing. These small RNA molecules regulate gene expression, developmental transitions, metabolism, cell fate, and cell death. His research will examine new genes and pathways that modify miRNA biogenesis and activity to affect these critical developmental processes.
Yichen Xu, PhD, with his sponsor Davide Ruggero, PhD, at the University of California, San Francisco, focuses on the estrogen receptor α (ERα), a nuclear hormone receptor that is mutated and hyperactivated in over 70% of breast cancers. Hormone therapy drugs, such as tamoxifen, which target classic ERα signaling are highly potent; however, many patients eventually develop drug resistance. His proposed research will address a previously unknown role of ERα in breast cancer progression and therapy resistance, and may identify a potential second-line therapy to treat breast cancer.
Ziyang Zhang, PhD [HHMI Fellow], with his sponsor Kevan M. Shokat, PhD, at the University of California, San Francisco, is developing a new form of cancer immunotherapy with improved safety and controllability. Redirecting the immune system to launch attacks on tumor cells has emerged as an extremely promising approach to fight cancer. One such strategy, named bispecific T cell engager antibody (BiTE) has shown remarkable efficacy against blood cancers, but it is also associated with severe toxicity. Using tools of synthetic organic chemistry, he aims to build a "chemical switch" that can be used to rapidly tune the activity of BiTE, thus allowing the circumvention of toxic side effects without diminishing therapeutic potential. The ultimate goal of this project is develop a cancer immunotherapy that can be safely employed at doses effective for the treatment of solid tumors.
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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, 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 $320 million and funded over 3,550 young scientists. This year, it will commit approximately $17 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
CONTACT
Yung S. Lie, PhD
Deputy Director and Chief Scientific Officer
Damon Runyon Cancer Research Foundation
yung.lie@damonrunyon.org
212-455-0521