New York, NY (February 5, 2018) - The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting innovative early career researchers, named 15 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 six new recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists. This award provides additional funding to scientists completing a 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:
Ryan D. Baldridge, PhD (Damon Runyon-Fraternal Order of Eagles Fellow '14-'17)
University of Michigan, Ann Arbor
The goal of this research is to increase our understanding of the integral membrane protein quality control systems. These systems are involved in regulation of proteins in different cellular organelles. One of these systems, called endoplasmic reticulum associated degradation (ERAD), plays a central role in many cancer processes by regulating the levels of proteins involved in tumor growth and metastasis. A common feature of all types of cancer is survival during unfavorable conditions that would trigger apoptosis in normal cells. In many cases, the rapid growth rates of cancer cells can generate environments triggering cellular stress. The ERAD system is upregulated as a cellular response to mitigate stress by removing unnecessary proteins from cells. Dr. Baldridge aims to gain an improved understanding of ERAD mechanisms, which may lead to more effective cancer therapies in the future.
Liron Bar-Peled, PhD (Damon Runyon- Lallage Feazel Wall Fellow '14-'17)
The Scripps Research Institute, La Jolla
Dr. Bar-Peled studies how cancer cells adapt to stress environments, focusing on oxidative stress. His research focuses on understanding how cells sense and respond to specific changes in their environment by activating singling pathways that lead to uncontrolled growth. He recently studied a particular pathway in non-small cell lung cancer and identified a "druggable" protein that could be targeted with small molecules and disrupt this uncontrolled growth. He plans to pursue this specific target and use the same strategy for identifying druggable pathways in other cancers that currently lack effective therapies.
Chao Lu, PhD (Damon Runyon-Kandarian Family Fellow '14-'16)
Columbia University, New York
Eukaryotic cells develop sophisticated mechanisms to package and access our genetic information. Recent studies have shown that proteins involved in genome regulation are frequently altered in human cancers, which often display abnormal nuclear architecture, and raise the questions of whether, and how, aberrant chromatin organization facilitates tumor development. Collectively, Dr. Lu's previous work has identified the molecular mechanisms by which high-frequency mutations in chromatin regulators reprogram genome-wide chemical modifications of DNA and histones. He also demonstrated that chromatin mutations are pro-oncogenic through the blockade of cellular differentiation. These studies provide compelling evidence for a causal role of chromatin dysregulation in oncogenesis. He proposes a novel pathway of cancer initiation through accumulation of hyper-proliferative and differentiation-refractory tissue progenitor cells driven by epigenome abnormality. His goal is to apply these mechanistic insights to advance current molecular diagnosis, classification and treatment of human cancers.
Matthew P. Miller, PhD (Damon Runyon-HHMI Fellow '14-'18)
University of Washington, Seattle
Dr. Miller is investigating how cells ensure the correct partitioning of genetic material during cell division. Errors in this process occur in nearly all tumor cells and are the leading cause of miscarriages and congenital birth defects in humans. The vast majority of solid tumors have incorrectly positioned chromosomes, causing high levels of genomic instability and DNA damage. Very little is known about how chromosome segregation becomes so defective during tumorigenesis. His research is focused on elucidating the mechanisms of both accurate and defective chromosome segregation with the goal of determining whether there are opportunities for development of new cancer therapeutics.
Shruti Naik, PhD (Damon Runyon Fellow '14-'17)
The Rockefeller University, New York
Dr. Naik focuses on the fundamentally important interactions between the immune system, microbes, and adult skin tissue stem cells, and the consequences of such interactions for health and disease. She studies how stem cells in epithelial tissues such as the skin sense and cope with inflammatory stress. Her goal is to understand how inflammatory signals (either host-generated or microbial) provide adult stem cells with rapid, sensitive, and context-specific information, and how this process can go awry, potentially predisposing stem cells to diseases such as cancer. She hopes that her findings will facilitate the development of novel therapies.
Neel H. Shah, PhD (Damon Runyon Fellow '14-'18)
University of California, Berkeley
Tyrosine kinases are enzymes that act as "on" and "off" switches for signals in cells and are important in regulating cellular activity, such as cell division. They can become mutated, stuck in the "on" position, and cause unregulated growth of the cell, which is a necessary step for the development of cancer. Kinase inhibitors have been developed as cancer treatments, but they have not been sufficiently effective and are susceptible to drug resistance. Dr. Shah seeks to identify new activities and modes of regulation that distinguish oncogenic and non-oncogenic tyrosine kinases, with the goal of identifying more specific drug targets.
November 2017 Damon Runyon Fellows:
Aleksey (Alex) Chudnovskiy, PhD, with his sponsor Gabriel D. Victora, PhD, at The Rockefeller University, New York, studies "antigen presentation," an immune process by which dendritic cells capture antigens at the tumor site, migrate to the tumor-draining lymph nodes, and present tumor antigens to the effector CD4 and CD8 T cells that are responsible for anti-tumor responses. This is the first crucial step in successful cancer immunotherapy.
Yusong R. Guo, PhD [HHMI Fellow] with her sponsor Roderick MacKinnon, MD, at The Rockefeller University, New York, focuses on the Piezo channel, a molecular machine on the cell membrane that converts mechanical stimuli on the outside of the cell into electric signals inside the cell. Piezo channels are important in human cells to sense touch, maintain balance, and regulate blood pressure. High expression of Piezo channels can promote various types of cancer, including breast and gastric. By studying its atomic structure, she aims to determine the mechanism of how the Piezo channel is regulated, which may provide the framework for novel anti-cancer therapies.
John C. Janetzko, PhD, with his sponsor Brian K. Kobilka, MD, at Stanford University School of Medicine, Stanford, studies G protein-coupled receptors (GPCRs), a class of membrane-embedded proteins that relay signals about hormone and neurotransmitter binding to the inside of the cell. Several types of cancer cells hijack these proteins by keeping them in an active state (constitutively turned "on") in order to promote their growth and allow them to metastasize. His research will use structural and biophysical methods to understand how activated GPCRs are recognized by other proteins called GPCR kinases, and how these kinases might be exploited as new therapeutic targets in cancer.
Zhejian Ji, PhD [HHMI Fellow] with his sponsor Tom A. Rapoport, PhD, at Harvard Medical School, Boston, studies the function of a critical ATPase protein called p97 in an important cellular process called protein degradation, which regulates proteins and can promote cancer cell proliferation and survival. His goal is to understand the molecular mechanism of how p97 functions. A better understanding of p97 could ultimately benefit the development of anti-cancer drugs based on p97 inhibition.
Yunsik Kang, PhD, with his sponsor Marc R. Freeman, PhD, at Oregon Health and Science University, Portland, aims to identify mechanisms that eliminate unneeded cells in the brain. During animal development, extra neurons and neuronal connections are produced, but these unneeded neurons are selectively "eaten" by glia (another type of cell in the brain) in a process called phagocytosis. He will perform rapid genetic screens and cell type-specific manipulations, allowing him to quickly find new mechanisms that regulate phagocytosis. Understanding how cells are targeted for phagocytosis during development will help us learn how to harness these targeting mechanisms to eliminate cancer cells for therapeutic purposes.
Warakorn (Pete) Kulalert, PhD, with his sponsor Yasmine Belkaid, PhD, at the National Institutes of Health, Bethesda, focuses on how the skin is influenced by microbes. The skin is enriched with immune cells and highly innervated; nevertheless, the roles of neuroimmune crosstalk in cancer development and treatment remain largely unexplored. Sensory perception, especially pain sensation, is associated with cancer-related complications as well as chemotherapy. Because the microbiota plays a critical role in maintaining tissue homeostasis in the skin, he will explore whether sensory processing can also be modulated by the host-microbe interactions, particularly in the context of tumorigenesis and cancer treatment. These insights may provide novel tools to alleviate tumor progression and complications linked with cancer and chemotherapy, including pain sensation.
Christopher P. Lapointe, PhD, with his sponsor Joseph Puglisi, PhD, at Stanford University School of Medicine, Stanford, examines how the synthesis of proteins (translation) is controlled, as dysregulated translation is a ubiquitous feature of cancer. He is focused on a key challenge: how regulation that originates at the "tail" end of a messenger RNA (mRNA, a genetic molecule that encodes a protein) impacts the start of translation, which occurs near the beginning of the mRNA. His goal is to reveal and analyze dynamic pathways that underlie this fundamental mechanism to control gene expression. Using an integrated approach of single-molecule fluorescence microscopy, structural, and biochemical strategies, this research should yield important insights into how translation is precisely regulated and how it is disrupted in a wide array of cancers.
Lucy Liu, PhD, with her sponsor Norbert Perrimon, PhD, at Harvard Medical School, Boston, studies cachexia, a complex metabolic syndrome characterized by a rapid and irreversible loss of body mass, which significantly impedes disease treatment success. This body-wasting phenomenon is a common feature in many types of cancers, but the causes are unknown. She is investigating the tumor-derived signaling mechanisms that lead to systemic cachexia and muscle wasting. As no current therapies exist for the reversal or delay of cachexic symptoms, identifying the triggers that lead to systemic body mass loss is imperative to improve our understanding of all cancers and to identify putative drug targets.
Fangfei (Fin) Qu, PhD, with her sponsor Julien Sage, PhD, at Stanford University, Stanford, is using Small Cell Lung Cancer (SCLC), a highly metastatic and lethal subtype of lung cancer, as a model to gain a better understanding of brain metastasis. Brain metastases are the most common type of intracranial tumors; they cause morbidity and mortality in a large number of cancer patients worldwide. The lack of preclinical models for brain metastasis has hampered our ability to better understand how primary tumors spread to the brain and grow there. She will first develop novel models to study SCLC metastatic growth in the brain microenvironment. This research will suggest new targets for inhibiting growth of SCLC and other cancers at distal metastatic sites in the brain, paving the way for novel treatment approaches for cancer patients.
Romain L. Riscal, PhD, with his sponsor M. Celeste Simon, PhD, at the University of Pennsylvania, Philadelphia, aims to identify and characterize the molecular mechanisms by which a key enzyme involved in cellular metabolism, Fructose-1,6 bisphosphatase (FBP1), suppresses Hepatocellular Carcinoma (HCC) liver cancer initiation and progression. Recent findings comparing HCC tumors and adjacent normal tissues reveal that FBP1 is consistently underexpressed in HCC tumors, functioning as a tumor suppressor in this setting. Since liver cancer is the third most frequent cause of cancer deaths, his goal is to study more precisely how FBP1 opposes liver cancer progression and to help identify novel therapeutic targets for treating patients.
Esen Sefik, PhD [HHMI Fellow] with her sponsor Richard A. Flavell, PhD, at Yale University, New Haven, is examining the connection between obesity, cancer and the microbiome. An estimated 600 million people worldwide suffer from obesity, with 15-20% of deaths from cancer in the US alone linked to obesity. Recent studies in mice highlight the importance of intestinal bacteria and immune cells in obesity and colorectal cancer; however, these roles are not yet well characterized in humans. She will analyze how high fat diet and obesity-associated intestinal bacteria change intestinal immunity in mice that harbor the human immune system and the human microbiota. This will help engineer better-targeted, combined therapies to colorectal cancer, especially in cases where existing immunotherapy fails.
Christina M. Termini, PhD, with her sponsor John P. Chute, MD, at the University of California, Los Angeles, aims to improve the success of hematopoietic stem cell transplants, which are used in the curative treatment of the majority of patients with leukemia or lymphoma. Prior to transplant, patients must undergo radiation therapy to decrease the number of cancerous blood cells. In order for hematopoietic stem cells to effectively repopulate the blood and immune systems of the transplant recipient, the stem cells must reach the bone marrow where they can expand. Her research focuses on how radiation impacts stem cell repopulation following transplant. Using in vivo transplantation models and super-resolution microscopy techniques, she will visualize and quantify how molecules called proteoglycans regulate stem cell interactions with the bone marrow. Her aim is to identify molecular targets that can be used to accelerate patient recovery following transplantation.
Linda T. Vo, PhD, with her sponsor Jeff A. Bluestone, PhD, at the University of California, San Francisco, focuses on T cell-based cancer immunotherapy, such as chimeric antigen receptor "CAR" T cells, as a transformative therapeutic approach. While recent studies have demonstrated the efficacy of CAR-T cell therapy in treating certain leukemias and lymphomas, further advancements are required to broaden its therapeutic utility. Pluripotent stem cells (PSCs) have the capacity to generate any cell type of the body and represent a potentially inexhaustible source of clinically useful cells. Using a novel strategy to promote the continuous generation of T cell progenitors from PSCs, she will engineer "off-the-shelf" T cells with improved tumor-recognition capability from stem cells. The successful generation of potent, dual-antigen specific T cells from PSCs in large quantities as an off-the-shelf product would be invaluable to the widespread application of T cell-based immunotherapies.
Jing Lin (Lucy) Xie, PhD [The Mark Foundation for Cancer Research Fellow], with her sponsor Daniel F. Jarosz, PhD, at Stanford University, Stanford, focuses on uncovering mutation-independent mechanisms of drug resistance in cancer. The prevalence of drug resistance in tumors - and collateral damage to healthy tissues - have been major roadblocks to improving the efficacy of chemotherapy. While current research has been focused on identifying mutations that confer cancer drug resistance, an emerging paradigm is that mutation-independent changes in the chromatin or proteins could be a hidden force that promotes the development of drug resistance. Her goal is to identify and characterize the heritable "molecular memories" that can confer a fitness advantage during future exposure to chemotherapeutics and other stresses.
Chuchu Zhang, PhD, with her sponsor Stephen D. Liberles, PhD, at Harvard Medical School Dr. Zhang aims to understand how the sensory organ called Area Postrema (AP) detects and generates nausea. Intense and protracted nausea and vomiting are major side effects of cancer therapy, with current anti-emetic drugs demonstrating only limited efficacy. She plans to focus on a particular group of neurons in AP that are potentially involved in nausea responses and use techniques to map and manipulate this circuit to reveal the neuronal substrates for nausea sensation in the brain. This project will advance our basic understanding of how nausea-inducing stimuli are detected and processed, and may lay the foundation for developing new treatment strategies.
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 $340 million and funded over 3,650 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
Yung S. Lie, PhD
Deputy Director and Chief Scientific Officer
Damon Runyon Cancer Research Foundation