Grants totaling nearly $4.16M give early career investigators independence to pursue novel ideas
New York, NY (July 15, 2017) – The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting innovative early career researchers, named 18 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 ($231,000 each) to work on innovative projects that have the potential to impact cancer prevention, diagnosis, and treatment.
May 2017 Damon Runyon Fellows:
Laura Blanton, PhD [Lallage Feazel Wall Fellow], with her sponsor David C. Page, MD, at Whitehead Institute for Biomedical Research, Cambridge, is focusing on the contributions of the X and Y chromosomes to immune cell gene expression and function. Since the immune system plays a crucial role in tumor biology and cancer treatment, this work will help illuminate differences between cancer susceptibility, progression, and treatments in men and women.
Andrew A. Bridges, PhD [HHMI Fellow] with his sponsor Bonnie L. Bassler, PhD, at Princeton University, Princeton, studies how bacterial cells form communities called biofilms that have particular three-dimensional architectures. He is investigating how the bacterial cell-cell communication process called quorum sensing drives the spatio-temporal gene expression patterns that govern biofilm formation. Biofilm bacteria are implicated as causal in various cancers and, furthermore, cancer patients receiving chemotherapy frequently suffer from infections caused by bacteria that rely fundamentally on biofilm formation for pathogenesis. By discovering the quorum-sensing program that bacteria execute to sculpt biofilm architectures, he hopes to contribute to the development of new strategies to interfere with formation of these bacterial communities.
J. Brooks Crickard, PhD, with his sponsor Eric C. Greene, PhD, at Columbia University, New York, is using high-throughput single molecule imaging to rebuild and visualize the process of homologous recombination (HR) in real time. DNA is subjected to many insults leading to damage. This DNA damage leads to a loss in genomic integrity, resulting in the formation and metastasis of many types of cancer. To guard against DNA damage, cells have developed several complex regulatory networks devoted to repair of damaged DNA, including HR. HR involves the search and pairing of one damaged piece of DNA to similar or identical DNA sequences to promote repair of the damaged piece, thus maintaining genome integrity. He seeks to understand, at the most basic biochemical level, how two of the key protein components in HR, Rad51 and Rad54, function to find and repair damaged DNA. His findings will give new insights into how cells fix damaged DNA, which may be key to the development of novel treatments and therapeutic options for all types of cancer.
Anne E. Dodson, PhD, with her sponsor Scott G. Kennedy, PhD, at Harvard Medical School, Boston, is investigating how defects that are not strictly based on DNA mutations can be passed from parent to progeny for multiple generations. Germ cells, the producers of eggs and sperm in animals, normally transmit the blueprint for life from parent to progeny. When germ cells acquire defects, however, these defects may also pass from parent to progeny. These underexplored defects may contribute to the onset and inheritance of familial cancer syndromes, and a better understanding of them could result in new cancer therapies.
Phillip A. Dumesic, MD, PhD, with his sponsor Bruce M. Spiegelman, PhD, at Dana-Farber Cancer Institute, Boston, seeks to understand how physical exercise promotes health. In addition to strengthening skeletal muscle, exercise also benefits distant organ systems, providing protection from metabolic disorders and chronic diseases including cancer. These widespread effects highlight muscle’s ability to communicate via secreted signals. However, the ability to pharmacologically modulate these signals for therapeutic gain is challenged by our limited understanding of their identities and mechanisms of action. By identifying muscle-derived signaling factors involved in muscle homeostasis and systemic metabolism, this research promises to suggest new avenues for therapy against cancer-associated cachexia, a condition of muscle wasting and perturbed metabolism.
Tikvah K. Hayes, PhD [David M. Livingston, MD, Fellow] with her sponsor Matthew L. Meyerson, MD, PhD, at Dana-Farber Cancer Institute, Boston, is focused on understanding and identifying mechanisms of resistance to cancer therapies. Why some cancers respond to some therapies at first, but later become unresponsive, is not well understood. Small cell lung cancer is an ideal cancer to investigate how and why chemotherapy, the oldest and most prescribed cancer regimen, initially causes tumor reduction but ultimately fails after some period of time. She will use a multifaceted approach to interrogate chemotherapeutic resistance with the goal of identifying new methods to enhance patient treatment.
Victoria Hung, PhD, with her sponsor Maria Barna, PhD, at Stanford University, Stanford, focuses on a central question in cell biology: how gene expression is spatially and temporally regulated to give rise to cell types and functions. Historically, the ribosome has been viewed as a molecular machine of invariant composition that passively and constitutively translates mRNA to protein. She is studying how phosphorylation of ribosomal components may endow ribosomes with specificity for certain transcripts and unique cellular functions. This work will also provide insight into how ribosome-mediated gene expression may play a role in cellular transformation for many different cancers, and in particular, lymphomagenesis.
Evan C. Lien, PhD, with his sponsor Matthew Vander Heiden, MD, PhD, at the Koch Institute for Integrative Cancer Research, Cambridge, is studying how diet and nutrition impact cancer cell metabolism and tumor progression. The way cancer cells utilize nutrients to support their growth and proliferation is determined not only by cancer-promoting genetic alterations, but also by the tumor’s interactions with its local environment. Diet-mediated changes in whole-body metabolism and nutrient availability are an important part of a tumor’s metabolic environment, and a better understanding of how diet modulates nutrient availability and utilization by cancer cells is needed. Moreover, the question of whether certain diets may improve prognosis is of great importance to cancer patients. He aims to provide insight into which cancer types respond to various diets, how diet impacts cancer cell metabolism to mediate these responses, and whether dietary interventions may open new therapeutic opportunities in combination with current cancer treatments.
Monica E. McCallum, PhD, with her sponsor Emily P. Balskus, PhD, at Harvard University, Cambridge, studies a compound, called alanosine, which exhibits anti-cancer activity against cells from sarcomas, mesothelioma, and pancreatic cancer. This compound is produced by a soil-dwelling bacterium. She seeks to elucidate how bacteria produce alanosine. Understanding the genes and enzymes that assemble this molecule will guide the discovery of additional novel chemotherapeutic agents that may be produced by bacteria.
Andrew C. Murley, PhD [HHMI Fellow] with his sponsor Andrew G. Dillin, PhD, at the University of California, Berkeley, is studying how the rapid growth of cancer cells exerts damaging stress on their subcellular compartments. In many cells, chronic stress of one of these compartments, called the endoplasmic reticulum, leads to cell death, but many types of cancer cells are able to avoid this fate. Recent findings point to the existence of secreted molecules released by cells when they are subjected to this stress. These molecules, whose identities are still unknown, can activate processes in neighboring cells, or in the secreting cells themselves, which protect them from this chronic stress. His goal is to identify these molecules and explore their role in cancer cell survival and other normal bodily functions.
Deepshika Ramanan, PhD, with her sponsor Christophe Benoist, MD, PhD, at Harvard Medical School, Boston, studies the interplay between commensal microbes and immune cells in the intestine, and how these interactions influence the progression of inflammation and colorectal cancer. Her research particularly focuses on a cell type that dampens inflammatory responses, known as regulatory T cells. In the intestine, these cells can be broadly categorized into two subsets that differ in origin and responsiveness to microbes, but their exact functions remain unclear. She aims to identify the specific functions of these different subsets in intestinal inflammation, tissue repair, and tumor pathogenesis. These studies could provide invaluable information that can be harnessed to improve current cancer immunotherapy options.
Jeremy I. Roop, PhD [Fayez Sarofim Fellow], with his sponsor Julie M. Overbaugh, PhD, at Fred Hutchinson Cancer Research Center, Seattle, seeks to advance HIV vaccine design efforts by studying the unique antibody response of infants infected with HIV. The 36 million people worldwide who are infected with HIV are at an increased risk for many forms of cancer. Infants who acquire HIV from their mothers rapidly develop broadly active antibodies that are capable of neutralizing a wide diversity of global HIV strains. An understanding of the developmental processes involved in eliciting this broad and potent response may reveal clues vital to vaccine design efforts. His research will develop a novel experimental protocol that will allow a detailed characterization of these infant antibodies, as well as reveal insights into the unique developmental processes by which they arise.
Benjamin R. Sabari, PhD, with his sponsor Richard A. Young, PhD, at Whitehead Institute for Biomedical Research, Cambridge, studies how the three-dimensional architecture of the genome plays a critical role in gene control and is altered in cancer through non-coding mutations. While many well-defined protein-coding mutations have been identified in T cell acute lymphoblastic leukemia (T-ALL), ongoing whole-genome sequencing efforts of patient T-ALL samples are revealing an unexpected level of non-coding mutations within regulatory elements critical for genome architecture. Dr. Sabari is studying how these patient mutations alter the architecture of the genome, lead to alterations in gene control and subsequent development of T-ALL. He will perform comparative analyses of three-dimensional interaction networks in normal, transformed, and genetically engineered cell populations. These studies promise to reveal novel mechanisms of T-ALL initiation and maintenance.
Shaogeng (Steven) Tang, PhD [Merck Fellow], with his sponsor Peter S. Kim, PhD, at Stanford University, Stanford, is interested in discovering small-molecule inhibitor drugs that target human immune-checkpoint proteins, including programmed cell death protein 1 (PD-1), using a combination of biochemistry, protein engineering, structural biology and immunology approaches. These small-molecule inhibitors would offer safety advantages resulting from their much shorter half-lives as compared to FDA-approved monoclonal antibody therapies, and possibly also offer efficacy advantages resulting from increased penetration and distribution within the tumor microenvironment. His work has broad implications for the development of a novel methodology for small-molecule drug discovery and the design of new cancer immunotherapies.
Lan Wang, PhD, with her sponsor Peter Walter, PhD, at the University of California, San Francisco, studies tailed-anchored proteins, a class of membrane proteins that perform important physiological functions. Cells possess machinery that ensures the correct distribution of tail-anchored proteins to their specific organelle. Her research aims to understand how cells accurately distribute the tail-anchored proteins amongst their multiple organelles and what happens when such mechanisms fail.
Darryl A. Wesener, PhD, with his sponsor Jeffrey I. Gordon, MD, at Washington University, St. Louis, is studying how food processing by the community of tens of trillions of microbes (microbiota) that resides in the human gut influences nutritional status. Obesity, and its associated metabolic abnormalities, is associated with higher incidence of certain cancers, notably those affecting the colon, uterus, and breast. Transplantation of intact gut microbiota from obese humans into germ-free mice leads to increased fat gain and obesity-associated metabolic abnormalities. He will employ synthetic food particles and mice colonized with human gut microbial communities to uncover biochemical functions and food ingredients that promote establishment of a beneficial microbiota that promotes leanness and metabolic health.
Evan J. Worden, PhD, with his sponsor Cynthia Wolberger, PhD, at Johns Hopkins University, Baltimore, examines how the decision to “turn on” or “turn off” genes is determined by a highly coordinated series of events that rely on the chemical modification of histone proteins. Misregulation of histone modification can cause a variety of human cancers. Dr. Worden is using structural biology and biophysical approaches to understand how the precise patterning of histone modifications – the “histone code” – is established. He plans to study the regulatory mechanisms that control histone methylation, which is important for the formation of leukemias.
Xin Zhou, PhD [Merck Fellow] with her sponsor James A. Wells, PhD, at the University of California, San Francisco, is using a creative protein engineering approach to break the “size barrier” of protein studies. Precise understanding of cancer protein structures can greatly facilitate the understanding of the molecular mechanisms of cancer biology and guide the design of new drugs. Recently, electron cryomicroscopy (cryo-EM) rapidly emerged as a powerful tool to deliver high-resolution protein structures. However, it remains extremely difficult to be used for proteins under a certain size (100 kDa), because most small proteins lack intrinsic structural features required for accurate structure determination. A vast number of proteins, including numerous cancer-related proteins, are smaller than 100 kDa. The successful completion of her project will result in experimental tools that are useful for the entire scientific community and will help cancer biologists to study the structures of any proteins of interest.