Twenty brilliant early-career investigators will receive funding to pursue cutting-edge cancer research.

The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting brilliant, early career researchers, named 15 new Damon Runyon Fellows. 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 selected five new recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists who will each receive $100,000 toward their research. This award provides additional funding to scientists completing a Damon Runyon Fellowship Award who have greatly exceeded Damon Runyon’s highest expectations and are most likely to make paradigm-shifting breakthroughs that transform the way we prevent, diagnose and treat cancer.

“Historically, Damon Runyon Fellows have gone on to become leaders in cancer research, making discoveries that are not only consequential in their field but also for the lives of patients. We are excited to welcome these brilliant scientists from across the country into their ranks and honored to continue to support the work of these Breakthrough Scientist awardees,” said Yung S. Lie, PhD, President and CEO of the Damon Runyon Cancer Research Foundation.

2021 Recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists:

Andrew A. Bridges, PhD, (HHMI Fellow ‘17-’21) Princeton University, Princeton

Dr. Bridges studies how bacterial cells form communities called biofilms, three-dimensional structures that are implicated in multiple forms of cancer and can provide a breeding ground for infection in patients undergoing chemotherapy. He is investigating how a communication process inside bacterial cells called “quorum sensing” drives the gene expression patterns that govern biofilm formation. By discovering the quorum-sensing mechanism bacteria use to sculpt biofilm architectures, he hopes to contribute to the development of new strategies to interfere with formation of these bacterial communities.

Leeat Keren, PhD (Damon Runyon Fellow ‘17-’20), Weizmann Institute of Science, Rehovot, Israel

Dr. Keren is combining novel imaging methods with advanced computational analysis, artificial intelligence, and clinical collaborations to investigate how cells within the tumor microenvironment act as a system. She will apply multiplexed imaging and state-of-the-art image analyses to comprehensively characterize cancerous lesions in situ and functionally relate these features to system-level mechanisms such as immune evasion, tumor progression, metastasis, and response to therapy. The ultimate goal is to achieve in-depth understanding of the cancer process to contribute to the development of personalized treatments and diagnostics.

Nora Kory, PhD (HHMI Fellow ‘17-’19), Harvard T.H. Chan School of Public Health, Boston

Dr. Kory studies the role of mitochondria in metabolic homeostasis and signaling, with a focus on mitochondrial transporters. Mitochondria are critical organelles in metabolic functions, generating the energy and compounds needed to construct the building blocks of the cell. However, they have been hard to identify and even harder to study mechanistically. She will approach the problem using innovative functional genomics and metabolomics tools. As cancer cells rely on an increased supply of energy to fuel their rapid proliferation and ensure survival in the harsh tumor microenvironment, these studies aim to lay the groundwork for future development of metabolic inhibitors with potential chemotherapeutic value.

Kara L. McKinley, PhD (Damon Runyon Fellow ‘17-’19), Harvard University, Cambridge

Dr. McKinley studies how epithelial tissues generate the right cells in the right places as they renew and regenerate during adulthood. These cellular behaviors are frequently co-opted by cancer cells during tumorigenesis and metastasis. She focuses on two of the most dynamic organ systems in mammals: the small intestine and the uterus. Together, these systems provide powerful complimentary models to reveal unifying principles of regeneration, as well as to identify key aspects of organ-specific physiology. She will use high-resolution live microscopy to watch regeneration in real time, and use a variety of genetic, molecular, and cell biological approaches to better understand these processes. Together, this work will reveal key mechanisms of epithelial remodeling and generate therapeutic insights.

Deepshika Ramanan, PhD (National Mah Jongg League Fellow ‘17-’21), Harvard Medical School, Boston

Dr. Ramanan studies the interplay between commensal microbes and immune cells in the intestine, and how these interactions influence the progression of inflammation and colorectal cancer. Immune fitness of an individual is thought to be the result of ongoing interactions between genetics and microbial exposure. A fundamental and often overlooked aspect of immunity, however, is the effect of maternal and environmental factors in early life. She uncovered a novel mode of non-genetic multigenerational transfer of immune traits (entero-mammary axis). She will utilize this tool to understand how maternal factors can modulate immune responses to infections, inflammation, and colorectal carcinoma.

November 2020 Damon Runyon Fellows:

Lauren E. Cote, PhD,with her sponsor Jessica L. Feldman, PhD, at Stanford University, Stanford, is exploring embryonic development to better understand how cells cooperate and build complex tissues. Since cancer cells often erroneously redeploy developmental programs and behaviors, her research into how neighboring cells align will yield insights into how cancerous cells metastasize and invade other tissues. Dr. Cote is combining tissue-specific genetic manipulations and laser cell ablations with live imaging during Caenorhabditis elegans digestive tract development to reveal how intracellular organization in one cell type can influence the alignment, polarity, and function of cells in the neighboring tissues.

Timothy J. Eisen, PhD [David Ryland Fellow], with his sponsor John Kuriyan, PhD, at the University of California, Berkeley, studies how a class of enzymes known as the Tec kinases help to activate the immune response. Two of these kinases, Itk and Btk, are remarkably similar in sequence composition and structure but play distinct roles in immune cells. Dr. Eisen is using high-throughput methods to understand the differences between these enzymes. This work will also aid in the overall molecular understanding of Btk, which is a therapeutic target of B-cell lymphoma and is inhibited by the chemotherapeutic ibrutinib.

Rongxin Fang, PhD [HHMI Fellow], with his sponsor Xiaowei Zhuang, PhD, at Harvard University, Cambridge, develops multiplexed imaging techniques to illuminate how enhancers control gene expression at a single cell level. Enhancer alterations are widely spread in cancer, but there is limited understanding of how these enhancers vary between single cells and relate to oncogene expression.  Dr. Fang will generate single-cell regulatory networks to investigate how enhancer activities are disrupted in IDH-mutant cancers. The proposed work may help identify enhancer-based therapeutic targets for cancer treatment in the future.

Yajing Gao, PhD [The Mark Foundation for Cancer Research Fellow], with her sponsor Peter Tontonoz, MD, PhD, at the University of California, Los Angeles, studies how the tumor microenvironment influences anti-tumor immune responses. Her research focuses on lipid metabolism in cytotoxic T lymphocytes (CTLs), a specialized population of white blood cells that kill malignant cells. To defend against this attack, tumors release lipid metabolites that can incapacitate infiltrating CTLs. Consequently, these metabolites create an immunosuppressive environment and promote tumor progression. Dr. Gao aims to unravel the pathways utilized by these harmful lipids. She is also investigating whether modifying lipid metabolism in immune cells can unleash CTL response and accelerate tumor shrinking. These studies have the potential to identify new therapeutic targets that will improve immunotherapy.

Gabriel Muhire Gihana, PhD [The Mark Foundation for Cancer Research Fellow], with his sponsor Gaudenz Danuser, PhD, at the University of Texas Southwestern Medical Center, Dallas, investigates the role of cellular morphology in mediating the oncogenic signaling of the gene RAS in pancreatic cancer. RAS is altered in more than 30% of human cancers, making it one of the genes most affected by cancer-causing alterations. Oncogenic RAS induces pronounced changes in cell morphology. Dr. Gihana aims to understand how the changes in cell morphology contribute to the potential of RAS to cause cancer. Because direct inhibition of oncogenic RAS has been difficult to achieve, these studies of other cellular parameters that mediate RAS impact on cancer is likely to contribute to novel and effective therapies.

Nir Hananya, PhD [Robert Black Fellow], with his sponsor Tom Muir, PhD, at Princeton University, Princeton, is investigating a component of the DNA repair machinery termed protein ADP-ribosylation. Our cells are constantly exposed to chemicals and electromagnetic radiation harmful to DNA. Since the integrity of our genetic material is critical, cells have evolved a variety of mechanisms to repair lesions in the DNA. But defects in these DNA repair pathways caused by genetic mutations can lead to genomic instability, which drives cancer development. Dr. Hananya is utilizing chemical biology to study ADP-ribosylation and to delineate its role in DNA repair. The research will provide vital information regarding cancer genesis and progression and will contribute to the development of new therapies.

Nicholas N. Jarjour, PhD, with his sponsor Stephen C. Jameson, PhD, at the University of Minnesota, Minneapolis, is searching for novel methods to overcome resistance to immunotherapy. While immunotherapies have had a transformative impact for some patients suffering from specific cancers, some tumors are highly resistant to these treatments. These resistant tumors often lack the majority of immune cell types that could potentially attack the tumor. Dr. Jarjour is addressing this problem by developing antigen-independent methods to stimulate the innate proliferative capacity of tissue-resident CD8+ T cells, based on signaling molecules called cytokines. His generalizable approach could increase the efficacy of existing checkpoint blockade therapies on resistant tumors. His work has implications for many types of cancer, as well as vaccine development.

Seungsoo Kim, PhD [HHMI Fellow], with his sponsor Joanna Wysocka, PhD, at Stanford University, Stanford, is studying the molecular links between cancer cells undergoing metastasis and formation of the face during development (known as craniofacial development). Both craniofacial and cancer cells must enter a migratory state triggered by certain key transcription factors including TWIST1. However, the exact role of TWIST1 appears to vary across cell types, which might explain some of the differences between cells found in various cancers and in normal craniofacial development. Dr. Kim is using genomic tools to dissect how transcription factor cooperation may toggle TWIST1 function across cell types, with potential implications for all cancers.

Aaron E. Lin, PhD,with his sponsors Alexander Ploss, PhD, and Brittany Adamson, PhD, at Princeton University, Princeton, is studying how hepatitis C virus (HCV) rewires cell biology and causes liver cancer. Modern HCV antiviral therapies are effective in curing hepatitis, but puzzlingly, recovered patients sometimes still develop cancer. This suggests that infection and subsequent inflammation permanently alter liver cells, but how this leads to cancer remains unclear. Dr. Lin is developing a CRISPR-based molecular “recorder” to determine whether cells that become more cancer-like have a history of infection and inflammation. This technology could identify genes that predispose healthy liver cells to infection, chronic immune stimulation, and transformation to cancer cells, which could point to potential therapeutic targets to interrupt the development of liver and other cancers.

Fangyu Liu, PhD, with her sponsor Brian Shoichet, PhD, at the University of California, San Francisco, is developing computational methods to screen compounds for pain-relieving effects. Pain is one of the common symptoms of cancer, but current effective analgesics (such as opioids) can come with significant side effects and pose a risk of misuse. These issues present a pressing need to develop novel analgesics with fewer drawbacks. Dr. Liu aims to develop methods to find molecules that target multiple nodes in the pain pathway to achieve analgesic synergy and reduce toxicity. This research has the potential to discover novel molecules for treatment of pain.

Conor J. McClune, PhD [HHMI Fellow], with his sponsors Elizabeth S. Sattely, PhD, and Polly M. Fordyce, PhD, at Stanford University, Stanford, investigates plant biosynthesis of therapeutic compounds. Approximately half of FDA-approved chemotherapeutics, including first line drugs like paclitaxel (Taxol) and vinblastine (Velban), derive from the arsenal of defensive chemicals that plants synthesize. Unfortunately, both the discovery of new plant-derived therapies and their scalable production are limited by intrinsic challenges of plant biology and genomics. Dr. McClune is developing systematic methods for identifying the biosynthetic pathways plants use to produce defensive molecules. Using single-cell technology, he will characterize rare cells responsible for synthesizing potentially beneficial chemicals and identify the enzymes they use to produce such molecules.

Stefan Niekamp, PhD [Dennis and Marsha Dammerman Fellow], with his sponsor Robert Kingston, PhD, at Massachusetts General Hospital, Boston, studies how gene expression programs are regulated in normal and cancer cells. The ability to switch specific genes “on” and “off” is partly encoded by multiprotein complexes competing for access to target DNA sequences in chromatin structures. The relative distribution of these activating or repressive complexes along chromatin regulates gene expression, and a shift in the balance of these complexes is a hallmark of many cancers. Dr. Niekamp aims to determine how chromatin accessibility is achieved by the competition between activating and repressive complexes, and to understand how well-known cancer mutations disrupt the fine-tuned balance.

Minhee Park, PhD, with her sponsors Alistair N. Boettiger, PhD, and Howard Y. Chang, MD, PhD, at Stanford University, Stanford, studies the interplay between the way chromatin is folded inside the nucleus and the role it plays in epigenetic regulation that creates cellular memory. Abnormal epigenetic regulation causes a broad range of diseases, including cancer. Using super-resolution imaging of chromatin structure, single-cell sequencing methods, and genetic approaches, Dr. Park aims to define the functional role of higher-order 3D chromatin organization in epigenetic memory regulations at single-nucleus resolution. This work has the potential to establish new layers of epigenetic regulation and may lead to new cancer therapies.

Parker L. Sulkowski, PhD [HHMI Fellow], with his sponsor William G. Kaelin, Jr., MD, at Dana-Farber Cancer Institute, Boston, investigates how solid tumors exist within dynamic microenvironments. Tumor cells hijack cell-to-cell communication mechanisms to interact with one another and their host to promote their growth. Dr. Sulkowski will study VHL deficient clear-cell renal cell carcinoma, the most common form of kidney cancer with more than 400,000 annual diagnoses worldwide. He will mechanistically investigate a novel phenomenon of active histone H3 secretion by cancer cells. By understanding the complex ways by which cancer cells interact with each other and their environment, this research could create new opportunities for cancer diagnosis and treatment.

Gokhan Unlu, PhD, with his sponsor Kivanc Birsoy, PhD, at The Rockefeller University, New York, studies how cancer cells adapt to nutrient limitations in their environment. High metabolic demands of proliferating cancer cells create metabolic bottlenecks for in vivo growth within solid tumors. Dietary and pharmacological interventions could provide unique opportunities to target such metabolic liabilities. However, studying tumor metabolism in vivo adds many layers of biological complexity, meaning these potential targets are currently poorly characterized. Dr. Unlu plans to combine metabolomics approaches and functional CRISPR screens to systematically identify metabolites limiting for in vivo tumor growth and metastasis.