Grants totaling over $4.39M give early career investigators independence to pursue novel ideas

New York, NY (January 21, 2016) – The Damon Runyon Cancer Research Foundation, a non-profit organization focused on supporting innovative early career researchers, named 19 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 ($208,000 each for basic scientists, $248,000 for physician-scientists) to work on innovative projects.

The Committee also named four 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:

Gira Bhabha, PhD (Damon Runyon Fellow ‘12-‘15)

University of California, San Francisco

Dr. Bhabha is focusing on understanding the function of structures on the cell surface called cilia, which play important roles in signaling, sensing the cell’s environment, and regulating cell growth. One particular signaling pathway in cilia, Hedgehog, has been shown to be dysregulated in multiple cancers, including basal cell carcinoma, medulloblastoma, and pancreatic cancer. She aims to characterize the structure and dynamics of the large, multi-protein complexes that function within the cilia. These findings will give insight into the role of cilia in cancers.

Alistair N. Boettiger, PhD (Damon Runyon Fellow ‘12-‘16)

Harvard University, Cambridge

Dr. Boettiger uses new high-resolution imaging technology to visualize the spatial arrangement of the genome in individual cells. Alterations in the physical structure of the genome affect gene expression and cell behavior. He aims to explain how mutations and genome structure changes give rise to malignancy and treatment resistance in cancer cells.

Mingye Feng, PhD (Damon Runyon Fellow ‘12-‘15)

Stanford University, Stanford

Dr. Feng studies the mechanisms by which tumors evade immune surveillance (detection by cells of the immune system) during cancer progression and metastasis. He has identified a critical role for cells called macrophages in immune surveillance, and he will continue to characterize their function in tumor cell recognition and destruction. An understanding of these processes could give rise to novel therapeutic strategies to prevent cancer metastasis.

Ralph E. Kleiner, PhD (Damon Runyon Fellow ‘12-‘14)

The Rockefeller University, New York

Dr. Kleiner is pursing interdisciplinary research that combines chemical biology, cell biology, and proteomics approaches to study how cells handle damage to their DNA and RNA. His goal is to identify and develop new molecules that can inhibit these pathways. Several existing anti-cancer therapies damage DNA and RNA or block DNA repair pathways, and more effective inhibitors of these pathways may hold therapeutic promise. 

November 2015 Damon Runyon Fellows:

Philip B. Abitua, PhD, with his sponsor Alexander F. Schier, PhD, at Harvard University, Cambridge, focuses on cellular signaling pathways crucial for the growth, differentiation, and morphogenesis of all tissues during embryonic development. Interestingly, many of these pathways are dysregulated in cancer cells. The same signals involved in normal development have also been found to enhance malignancy. He aims to elucidate the molecular mechanisms driving cell motility initiated by the signaling molecule Toddler and to characterize the function of newly identified signal proteins that affect cancer progression.

Corina E. Antal, PhD, with her sponsor Ronald M. Evans, PhD, at the Salk Institute, La Jolla, aims to develop ways to increase the efficacy of pancreatic cancer chemotherapy. The reason for pancreatic cancer drug resistance is the presence of a dense, supportive tissue surrounding the cancer cells. She is using multiple high-throughput approaches to identify and target key genes within this tissue in order to reduce its supportive role. This work will aid in developing therapies to increase the delivery of the chemotherapeutic drugs to the tumor, allowing immune cells to infiltrate the tumor and kill cancer cells.

Harihar Basnet, PhD, with his sponsor Joan Massagué, PhD, at the Memorial Sloan Kettering Cancer Center, New York, is investigating the mechanisms responsible for cancer relapse. During cancer progression, cancer cells can spread to secondary sites where they can stay latent for months to decades before developing into metastases. His goal is to identify the genes that are important for regulating latency in metastatic cancer cells. This study will uncover potential therapeutic targets to eliminate latent metastatic cells and thus prevent cancer relapse.

Brian J. Beliveau, PhD [HHMI Fellow] with his sponsor Peng Yin, PhD, at Harvard University’s Wyss Institute for Biologically Inspired Engineering, Boston, is using newly developed “super-resolution” microscopy methods to look at DNA structure in cells. These new methods may provide a clearer picture of the difference between the structure of genes that are “on” and genes that are “off.” As many cancers are driven by the abnormal expression of genes such as oncogenes and tumor suppressors, information about how DNA structure can turn genes on and off may aid in the development of cancer therapies.

Justin A. Bosch, PhD, with his sponsor Norbert Perrimon, PhD, at Harvard Medical School, Boston, is studying the molecular language of cell-cell communication, an essential function of animal cells that coordinates normal tissue development and function that is frequently misregulated in many cancers. By developing novel methods to study the biological functions of an extraordinary class of intercellular messages—those that transfer directly into the interior of recipient cells—he will gain new insight into fundamental modes of cell-cell communication. His research will improve our understanding of the molecular events leading to cancer progression, leading to development of improved methods to deliver drugs into cells.

Christopher J. Cambier, PhD [HHMI Fellow] with his sponsor Carolyn R. Bertozzi, PhD, at Stanford University, Stanford, studies the role of cells called macrophages in mediating inflammation in immune responses to cancer. He is using the Mycobacterium marinum/zebrafish model of infection to examine misguided immune responses, many of which are shared with cancer. In particular, he proposes to study the distribution of a mycobacterial glycolipid molecule that is associated with driving macrophage activation and death, and will visualize the interactions of these glycolipids with macrophages in a living system. This new imaging approach along with the ability to manipulate host and pathogen genetics in a controlled setting will shed light on the inflammatory mechanisms driving disease.

Lindsay B. Case, PhD, with her sponsor Michael K. Rosen, PhD, at the University of Texas Southwestern Medical Center, Dallas, is establishing an in vitro experimental system to study the formation of integrin signaling complexes on model membranes. Integrins form multiprotein signaling complexes that are essential for the survival, growth, and migration of tumor cells; integrins and their associated proteins are commonly mutated or misregulated in diverse cancer types. She will elucidate the molecular interactions and physical mechanisms that regulate the assembly of  integrin complexes to potentially reveal novel strategies for disrupting integrin signaling in cancer.

John D. Leonard, PhD, with his sponsors Erin J. Adams, PhD, and Peter A. Savage, PhD, at The University of Chicago, Chicago, focuses on regulatory T cells—immune cells that normally prevent autoimmunity, but are co-opted by cancers in order to evade anti-tumor immune attack. He will use a combination of biochemistry, structural biology, and mouse models in order to understand how regulatory T cells recognize “self,” and how this process is exploited in prostate cancer. His results will inform efforts to develop therapies that disrupt the ability of cancer cells to recruit and activate regulatory T cells, thereby releasing the "brakes" and allowing the immune system to fight tumors more effectively.

Zhuobin Liang, PhD, with his sponsors Patrick Sung, DPhil, and Gary M. Kupfer, MD, at Yale University School of Medicine, New Haven, is investigating the novel involvement of the Fanconi anemia DNA repair pathway in coordinating DNA replication and RNA transcription to maintain genome stability. Fanconi anemia (FA) is a multigenic disorder marked by progressive bone marrow failure and a strong cancer predisposition. He is employing a combination of biochemical and in vivo approaches to study the mechanism by which FA proteins attenuate aberrant DNA and RNA lesions to prevent cancers. This research promises to shed light on critical processes of genomic surveillance as well as of oncogenesis and hematopoiesis.

Alesia N. McKeown, PhD [HHMI Fellow] with her sponsors Nels C. Elde, PhD, and Cedric Feschotte, PhD, at the University of Utah School of Medicine, Salt Lake City, studies the innate immune system and its key role in suppressing many types of cancers. It is unclear why some cancers respond well to immunity-based therapies while others escape treatment and continue to spread. Her research is aimed at characterizing a new layer of host immunity composed of retrogenes of essential host proteins. She believes that these retrogenes act to inhibit viral infection by acting as nonfunctional “decoys” of host proteins required for the viral life cycle. By investigating how these decoys exert their antiviral function, she hopes to better understand the landscape of host immunity and utilize these new genes as potential therapeutics to halt similar pathways involved in cancer progression.

Nikhil Sharma, PhD, with his sponsor Stephen Liberles, PhD, at Harvard Medical School, Boston, studies a specialized group of cells called neuroepitheal bodies (NEBs) from which lung tumors are often derived. NEBs are thought to serve as critical detectors of chemical and mechanical stimuli that enter the lung and are the main targets of nerve fibers entering the lung. He hopes to characterize the function and dysfunction of NEBs and NEB-innervating neurons in order to better understand and treat lung cancer.

Niranjan Srinivas, PhD, with his sponsors Hernan G. Garcia, PhD, and Adam P. Arkin, PhD, at the University of California, Berkeley, is combining new live imaging technologies, synthetic biology, and mathematical modeling to quantitatively analyze gene expression patterns in space and time during development. Predictive understanding of such patterns and how they go awry during mutations could help us uncover the molecular mechanisms underlying diseases such as cancer. Combining such knowledge with the ability to synthetically alter gene expression patterns could also lead to novel therapeutic approaches.

Benjamin M. Stinson, PhD, with his sponsors Johannes Walter, PhD, and Joseph J. Loparo, PhD, at Harvard Medical School, Boston, studies the mechanism of non-homologous end joining (NHEJ), the primary method used by our cells to repair DNA double strand breaks (DSBs), a particularly toxic form of DNA damage in which a single piece of DNA is completely broken into two pieces. He is examining how the NHEJ machinery modifies DNA at DSBs to allow re-joining of the DNA molecule. This work will contribute to our knowledge of cancer development and treatment, as defects in NHEJ result in predisposition to cancer, and a number of common cancer treatments introduce DSBs that are primarily repaired by NHEJ.

Seyed Fakhreddin Torabi, PhD, with his sponsor Joan A. Steitz, PhD, at Yale University, New Haven, is studying a highly abundant cellular long noncoding RNA (lncRNA) called MALAT1 (metastasis associated lung adenocarcinoma transcript 1), which serves as a prognostic factor in several human cancers.  MALAT1 is stabilized via formation of a complex triplex structure called expression and nuclear retention element (ENE). He aims to identify additional MALAT1-like ENEs in the genome through an in vitro evolutionary process in combination with bioinformatics studies. Novel ENEs may facilitate the discovery of novel cancer biomarkers and a better understanding of MALAT1 accumulation in cancer cells.

Albert G. Tsai, MD, PhD, with his sponsor Sean C. Bendall, PhD, at Stanford University, Stanford, is developing next-generation diagnostics for low abundance cellular cancer samples. By measuring 40 or more markers simultaneously on individual tumor cells deposited on glass slides, he hopes to enable definitive diagnoses of blood and lymph node cancers without the need for invasive surgery or a histopathology laboratory. These methods will also provide a unique way to study these cancers, by merging traditional light microscopy with automated antibody-based multi-marker analysis.

Peter M. Westcott, PhD, with his sponsor Tyler Jacks, PhD, at Massachusetts Institute of Technology, Cambridge, is developing improved in vivo models for studying the complex interactions between colorectal cancer and the immune system. The powerful genome editing technology CRISPR-Cas9 will be leveraged to rapidly generate a suite of novel mouse models of colorectal cancer harboring distinct mutational signatures seen in human cancer. He will use genome-wide sequencing and preclinical studies to dissect the role of these mutational signatures in promoting cancer cell detection by the immune system, and in modulating response to immunotherapies.

Jiaxi Wu, PhD, with his sponsor Jason G. Cyster, PhD, at University of California, San Francisco, is investigating the mechanism of dendritic cell (DC) missing-self recognition and migration. DCs recognize and present antigens to lymphocytes, a process that is essential for shaping host immune responses against infection and cancer. How DCs recognize altered self cells (such as cancer cells and pathogen-infected cells) remains poorly understood. These studies should significantly enhance our understanding of DC biology and eventually contribute to the development of new strategies to harness DC function for immunotherapy against cancer.

Yi Yin, PhD [William Raveis Charitable Fund Fellow] with her sponsor X. Sunney Xie, PhD, at Harvard University, Cambridge, is using newly developed state-of-the-art single cell sequencing technology to examine how DNA repair mechanisms go awry and contribute to cancer initiation and progression, as well as response to chemotherapy. Cancer cells usually have characteristic loss-of-heterozygosity, copy number variation and other types of genome rearrangements. A better understanding of the molecular mechanisms, genomic and cell contexts and effects from different allele variants in DNA repair genes of each individual may help guide treatment approaches for many cancer types, including breast, skin, and blood cancers.

Boris Zinshteyn, PhD [HHMI Fellow] with his sponsor Rachel Green, PhD, at the Johns Hopkins University School of Medicine, Baltimore, is using a combination of high-throughput genetic and biochemical techniques to identify the fundamental mechanisms underlying a process called nonsense-mediated decay (NMD). NMD enables cells to detect and destroy messages that are the result of potentially damaging genetic mutations. This process augments many genetic diseases and is important for cancer cells to adapt to the hostile tumor environment.