The Damon Runyon Cancer Research Foundation has named 16 new Damon Runyon Fellows, exceptional postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators. The prestigious, four-year Fellowship encourages the nation's most promising young scientists to pursue careers in cancer research by providing them with independent funding ($260,000 total) to investigate cancer causes, mechanisms, therapies, and prevention.

“We are thrilled to be funding these innovative, young scientists with the brilliance and passion to push boundaries and make breakthroughs. They are committed to understanding the fundamental processes driving cancer, which may ultimately lead to new therapeutic approaches for patients. Damon Runyon Fellows are the future leaders of their respective fields,” said Yung S. Lie, PhD, President and CEO of the Damon Runyon Cancer Research Foundation.

Spring 2022 Damon Runyon Fellows:

Xin Gu, PhD, with her sponsor Michael E. Greenberg, PhD, at Harvard Medical School, Boston

Regulation of gene transcription is a major mechanism cells use to modify the levels of certain proteins in response to their environment. A specific class of genes called immediate-early genes (IEGs) responds rapidly to external stimuli to adjust downstream gene transcription programs before any new proteins are synthesized. Abnormal expression of IEGs has been implicated in multiple types of cancers, as well as in neurological syndromes like addiction. Despite extensive study, the regulation of IEGs remains poorly understood. Dr. Gu’s work focuses on revealing the molecular mechanisms of IEG expression in cells and establishing model systems to study the physiological and disease-related outcomes caused by misregulation of this process. Dr. Gu received her PhD from MIT and her BSc from Peking University.

Cayla E. Jewett, PhD [Merck Fellow], with her sponsor Andrew J. Holland, PhD, at The Johns Hopkins University School of Medicine, Baltimore

Every cell contains specialized compartments called organelles that perform distinct functions, and cells employ counting mechanisms to finely tune organelle population. Centrioles are one type of organelle required for proper cell division and mammalian development. Cells normally contain two or four centrioles, depending on cell cycle state, and centriole gains or losses result in cancer. One exception to this rule are the cells that line our airways, brain ventricles, and reproductive tracts. These cells contain hundreds of centrioles—yet how these specialized cells break the rules of conventional cell cycle-regulated counting mechanisms remains a mystery. Dr. Jewett’s work utilizes primary cell culture and in vivo models to understand the molecular framework that allows increased numbers of centrioles in certain cell types. This work will advance our understanding of how defects in centriole growth cause human diseases such as cancer. Dr. Jewett received her PhD from the University of Colorado School of Medicine and her BS from the University of Denver.

Grace E. Johnson, PhD [HHMI Fellow], with her sponsor Bonnie L. Bassler, PhD, at Princeton University, Princeton

Dr. Johnson studies the role that a particular type of cell-cell communication, known as quorum sensing, plays in the development of spatially structured bacterial communities called biofilms. Biofilm formation promotes disease in many clinically relevant bacterial species, and infections caused by them pose severe risks for patients receiving chemotherapy. Dr. Johnson is currently investigating how quorum sensing within biofilms establishes patterns of gene expression, and in turn, how these patterns drive biofilm development and dictate biofilm architectural features. By defining mechanisms underlying biofilm formation and biofilm architecture, Dr. Johnson hopes to contribute to the generation of new approaches for disrupting quorum-sensing-controlled bacterial community interactions as a means of combating bacterial pathogens. Dr. Johnson received her PhD from MIT and her BS from Yale University.

Heidi E. Klumpe, PhD [Merck Fellow], with her sponsors Ahmad S. Khalil, PhD, and Mary Dunlop, PhD, at Boston University, Boston

Cells living in aggregates can perform more complex tasks than individual cells, but they also face key challenges as they have less access to space and nutrients. Tumors, like the healthy tissues they disrupt, must balance these physical forces and effectively distribute metabolites to continue to grow. Dr. Klumpe will use yeast as a simplified model of cell aggregation to engineer diverse aggregates and observe their growth and maintenance over many generations. Understanding how certain properties of an aggregate affect its long-term stability can shed light on “design principles” that underlie the persistence of tumors, as well as what stabilizes other multicellular structures, such as healthy tissue and biomaterials. Dr. Klumpe received her PhD from the California Institute of Technology and her BS/BA from North Carolina State University.

Ali Lashkaripour, PhD, with his sponsor Polly M. Fordyce, PhD, at Stanford University School of Medicine, Stanford

The astonishing diversity of T cells makes finding ones that specifically target tumor cells but not host cells a major challenge in developing T cell immunotherapies. For this reason, the adoption of T cell immunotherapies in clinical settings has been slow despite their remarkable potential. Dr. Lashkaripour is developing a microfluidic platform capable of screening millions of T cells against millions of tumor antigens per day to identify the stimulatory pairs that drive an efficient immune response. With this research, he hopes to establish the groundwork for deciphering the rules of sequence-dependent T cell recognition of antigens. This research may guide the development of more effective and safer cancer immunotherapies. Dr. Lashkaripour received his PhD from Boston University, his MSc from the University of Tehran, and his BSc from Ferdowsi University of Mashhad.

Tadashi Manabe, MD, PhD [Connie and Bob Lurie Fellow], with his sponsor Trever G. Bivona, MD, PhD, at University of California, San Francisco

Lung cancer remains the leading cause of cancer mortality. Substantial breakthrough discoveries, including the identification of lung cancer-specific genetic drivers (e.g., EGFR mutations, EML4-ALK fusion genes) and the development of molecular inhibitors of these pathogenic factors, have improved outcomes for patients with advanced-stage lung cancer. However, lung cancer cells eventually acquire resistance to these molecular inhibitors, resulting in progressive disease. Dr. Manabe’s research focuses on protein compounds formed by the self-assembly of oncogenic fusion proteins such as EML4-ALK. These compounds initiate a signaling pathway that causes abnormal cell proliferation in cancer. Dr. Manabe will explore the newly discovered structures of signaling proteins with the goal of developing molecular therapies that enhance precision medicine strategies and improve the control of lung cancer. Dr. Manabe received both his MD and PhD from Keio University School of Medicine.

J. Scott P. McCain, PhD, with his sponsor Gene-Wei Li, PhD, at Massachusetts Institute of Technology, Cambridge

Many organisms (including humans) have evolved circadian rhythms to adapt to the rising and setting of the sun, and recent discoveries point to circadian rhythms even in non-photosynthetic bacteria. Bacteria have a huge impact on human health, including cancer risk and treatment outcomes, and yet we may be missing a fundamental aspect of their nature. Dr. McCain is studying circadian rhythms in bacteria: how, why, and who? He is using modern genomics and classic genetics approaches to dissect how bacteria can “predict” their environment from day to day. He is also examining why bacteria do this—what are the costs and benefits of a circadian rhythm? Finally, he is looking broadly across bacteria to examine the prevalence of circadian rhythms. This project will provide fundamental insights into the biology of bacteria and circadian rhythms, both of which have direct implications for cancer biology. Dr. McCain received his MSc and PhD from Dalhousie University and his BSc from the University of Western Ontario.

Senén D. Mendoza, PhD [HHMI Fellow], with their sponsor Michael T. Laub, PhD, at Massachusetts Institute of Technology, Cambridge

In addition to acute illness, viruses can cause cancers. While our understanding of cellular immunity against viruses that have DNA-based genomes is robust, we know less about how cells protect themselves against RNA-based viruses such as hepatitis C, a leading cause of liver cancer. Because many cellular defenses against viruses are known to be shared between mammals and bacteria, Dr. Mendoza is looking for new cellular defenses against RNA viruses in bacteria and will investigate how these defenses work. The resulting discovery of anti-viral defenses will broaden our understanding of how cells protect themselves against RNA viruses, which will improve our capacity to support patients' immune systems when infected with cancer-causing RNA viruses. Dr. Mendoza received their PhD from the University of California, San Francisco, and their BS from the University of Miami.

Rebecca S. Moore, PhD [HHMI Fellow], with her sponsor Amita Sehgal, PhD, at the University of Pennsylvania, Philadelphia

Sleep problems may be a risk factor for developing certain types of cancer—lung, colon, pancreas, and breast—and may affect the progression of these cancers and the effectiveness of their treatment. Conversely, symptoms of cancer or side effects of treatment, including restless legs and obstructive sleep apnea, may cause sleeping problems, reducing quality of life. Understanding the complex relationship between cancer and sleep creates opportunities to improve health, treatment options, and quality of life. Specifically, understanding how the peripheral nervous system and the brain regulate both the timing and rhythmicity of sleep (i.e., circadian control), and the balance between time awake and growing sleep pressure (i.e., homeostatic control), could improve survival rates and the quality of cancer treatment. To this end, Dr. Moore aims to identify the role of circulating dietary cholesterol on sleep and to conduct a targeted genetic screen to identify peripherally secreted proteins that affect either the circadian or the homeostatic control of sleep. These results will provide a means for therapeutic interventions to ameliorate the effects of sleep disruption. Dr. Moore received her PhD from Princeton University and her MS and BS from the City College of New York.

Manuel Osorio Valeriano, PhD [Philip O'Bryan Montgomery, Jr., MD, Fellow], with his sponsors Lucas Farnung, PhD, and Danesh Moazed, PhD, at Harvard Medical School, Boston

Human cells compact their vast genomes into the small confines of the nucleus by wrapping their DNA into a highly complex structure called chromatin. Packaging DNA into chromatin, however, affects all nucleic acid-transacting machines (e.g., transcription factors) that need to access the genomic information stored in the DNA. NuRD is a large multi-subunit protein complex that plays a major role in making chromatin either accessible or inaccessible. Dysregulation of NuRD and aberrant targeting of the complex can result in the emergence of several types of cancers, including breast, liver, lung, blood, and prostate cancers. Dr. Osorio Valeriano’s work will reveal mechanistic aspects of NuRD-mediated chromatin regulation and pave the way for the development of novel therapeutic approaches that target cancers more effectively. Dr. Osorio Valeriano received his PhD from Philipps University and his MSc and BSc from the National Autonomous University of Mexico.

Dylan M. Parker, PhD [HHMI Fellow], with his sponsor Roy R. Parker, PhD, at University of Colorado Boulder

Dr. Parker studies the role of molecular assemblies known as stress granules that form when cells are exposed to stressful conditions. The assembly of stress granules upon cellular insult is thought to regulate gene expression and modulate cell survival. Notably, stress granules are present in various cancers and many chemotherapeutic treatments lead to the formation of stress granules. Dr. Parker aims to determine the mechanisms regulating stress granule assembly and disassembly to understand how stress granule formation supports the development of cancer and chemotherapy-resistant tumors. This research has the potential to discover novel targets to treat cancers as well as sensitize chemotherapy-resistant cancers to existing treatments. Dr. Parker received his PhD from Colorado State University and his BS from the University of Oregon.

Titas Sengupta, PhD [Rebecca Ridley Kry Fellow], with her sponsor Coleen T. Murphy, PhD, at Princeton University, Princeton

An organism’s life experiences, such as exposure to bacterial pathogens, can cause sustained changes in its physiology and behavior. How these experiences are encoded in heritable RNA and DNA-associated proteins (called chromatin), and how these in turn affect the physiology of the organism itself and its progeny, are not well understood. Previous research has shown that the roundworm C. elegans can “read” small non-coding RNAs from the pathogenic bacterium Pseudomonas aeruginosa and learn and teach its progeny to avoid this bacterium. Dr. Sengupta’s research investigates how bacterial small RNAs taken up in the intestine can result in lifelong, multigenerational, and organism-wide changes at the epigenetic (RNA and chromatin) level to regulate brain function and behavior. She will investigate which small RNA and chromatin-associated genes are required for the learned response, where these genes function, and what changes at the epigenetic and gene expression level underlie this response. This will inform principles of epigenetic regulation of gene expression following diverse environmental stimuli, and stimuli within tissue environments, including tumor microenvironments. Dr. Sengupta received her PhD from Yale University and her MS and BS from the Indian Institute of Science Education and Research.

Erron W. Titus, MD, PhD [Connie and Bob Lurie Fellow], with his sponsor Matthew F. Krummel, PhD, at University of California, San Francisco

Chimeric antigen receptor (CAR) T cells are immune cells that have been genetically engineered to bind specific proteins on cancer cells. CARs can display exquisite sensitivity and discrimination, and CAR T cells have been deployed with spectacular success to detect and kill blood cancers. Unfortunately, they are much less effective against “solid” tumors, such as breast or kidney cancers. To address this problem, Dr. Titus is designing T cells with membrane proteins that perform novel functions, including proteins that facilitate membrane fusion or alter the adhesion between T cells and their targets. By redesigning T cell membranes, Dr. Titus hopes to create useful cancer-fighting tools that can be deployed in conjunction with other emerging cellular therapies and immunotherapies. Dr. Titus received his MD and PhD from the University of California, San Francisco, and his AB from Harvard University.

Wen Mai Wong, PhD [Kenneth G. and Elaine A. Langone Fellow], with her sponsor Sreekanth H. Chalasani, PhD, at The Salk Institute for Biological Studies, La Jolla

Multiple cancers, including prostate, breast, and gastrointestinal cancers, are known to be heavily innervated. However, the role of neurons and their signaling within the tumor microenvironment remains unknown. Previous work has shown that transecting the vagus nerve can block the progression of gastric cancer, emphasizing a critical role for the vagal neurons in this disease. However, these transections produce side effects, making it a difficult strategy to translate to the clinic. Dr. Wong is proposing a new method to non-invasively silence neurons within the body. Specifically, she will use ultrasound to silence specific neurons in rodent models in order to determine the impact of these neurons on animal behavior and disease physiology, including the tumor microenvironment. Dr. Wong received her PhD from the University of Texas Southwestern Medical Center and her BS from St. Mary’s University.

Xiaowei Yan, PhD [Connie and Bob Lurie Fellow], with her sponsor Howard Y. Chang, MD, PhD, at Stanford University School of Medicine, Stanford

Extrachromosomal DNA (ecDNA), or DNA not attached to a chromosome, has been found in nearly half of human cancer types, especially in aggressive cancers such as glioblastoma, neuroblastoma, leukemia, lung, and ovarian cancer. Despite being a potent cancer driver, the mechanisms underlying ecDNA regulation remain largely unexplored. Combining both advanced imaging and cutting-edge sequencing technologies, Dr. Yan is investigating how ecDNA is spatially organized in cells and genetically inherited over generations. She hopes to reveal new mechanisms of DNA regulation and inheritance other than the canonical chromosome and help develop new ways to treat patients with ecDNA-driven cancers. Dr. Yan received her PhD from the University of California, San Francisco, and her BS from Peking University.

Xiphias Ge Zhu, PhD [HHMI Fellow], with his sponsor Stephen Elledge, PhD, at Brigham and Women's Hospital, Boston

Many immunotherapy strategies require patient T cells to recognize specific cancer-associated antigens. However, it is unclear what these antigens are and how they contribute to tumor shrinkage during treatment. Dr. Zhu will use large-scale antigen screening methods to identify cancer-associated antigens recognized by T cells that are activated in breast cancer patients during immunotherapy treatment. Mapping the antigen landscape of breast cancer will identify targetable antigens and improve future immunotherapies. Dr. Zhu received his PhD from The Rockefeller University and his BSc from the National University of Singapore.