Damon Runyon Cancer Research Foundation announces newest cohort of Fellows and Breakthrough Scientists

The Damon Runyon Cancer Research Foundation has announced its newest cohort of Damon Runyon Fellows, 13 outstanding postdoctoral scientists conducting basic and translational cancer research in the laboratories of leading senior investigators. This prestigious, four-year 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 six new recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists. This award recognizes Damon Runyon Fellows who have 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. To catapult their research careers-;and their impact-;Damon Runyon makes an additional investment of $100,000 in these exceptional individuals.

Being awarded the Dale F. Frey Breakthrough Scientist Award will allow me to take risks that I otherwise wouldn't have. That includes expanding into new approaches for me, like single molecule biophysics and functional genomics-;and purchasing essential equipment that has been held up by supply chain shortages!"

Allison Didychuk, PhD

Learn about the new Fellows and Breakthrough Scientists below.

2022 recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists:

Robert S. Banh, PhD, New York University Grossman School of Medicine, New York
"Codon- and nutrient-specific regulation of mRNA translation in pancreatic cancer"

In response to nutrient changes in the environment, pancreatic cancer cells can adjust the rate of mRNA translation to selectively regulate the rate of protein production. However, the specific codons-;the trinucleotide sequences that correspond to specific amino acids-;and regulatory mechanisms used are not known. Dr. Banh's research aims to decipher the laws governing how codons regulate mRNA translation in response to the nutrient environment in pancreatic cancers. As cancer cells have many codon-altering mutations and are constantly adapting to changes in the nutrient environment, these studies will offer insight into tumor evolution and may uncover novel therapeutic strategies for pancreatic and other cancer patients.

Allison L. Didychuk, PhD, University of California, Berkeley
New position: Assistant Professor at Yale University (starting 7/1/2022)
"Viral mimics of host transcription factors in oncogenic herpesviruses"

Kaposi's sarcoma herpesvirus (KSHV) is a human oncogenic virus and the causative agent of cancers including Kaposi's sarcoma, primary effusion lymphoma, and Multicentric Castleman disease. The related human herpesvirus Epstein-Barr Virus (EBV) is even more prevalent than KSHV, and is linked to cancers including Burkitt's lymphoma, Hodgkin's lymphoma, and nasopharyngeal carcinoma. Dr. Didychuk is investigating the mechanisms by which KSHV co-opts the cellular host machinery to produce its own gene products in a manner distinct from other viruses and host cells. A molecular understanding of how herpesviruses hijack the late gene transcription machinery will reveal new therapeutic weaknesses in the viral lifecycle and allow for structure-guided design of novel anti-viral drug targets.

Christopher P. Lapointe, PhD, Stanford University, Stanford
"Fundamental mechanisms that underlie human translation initiation and its dysregulation in cancer"

Dr. Lapointe studies how the synthesis of proteins (translation) is controlled, as dysregulated translation is a ubiquitous feature of cancer. He is focused on a key question: how regulation that originates at the "tail" end of a messenger RNA (mRNA) impacts the start of translation, which occurs near the beginning of the mRNA. His goal is to reveal and analyze 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 will yield important insights into how translation is precisely regulated and how it is disrupted in a wide array of cancers.

Dian Yang, PhD, Whitehead Institute for Biomedical Research, Cambridge
"Dissecting intratumoral heterogeneity and hierarchy at single cell resolution"

Dr. Yang is examining tumor heterogeneity in search of new diagnostic markers and potential therapeutic targets. A tumor consists of not only cancer cells, but also immune cells, fibroblasts, and other stromal components. The diverse cell types and cell states that form the tumor microenvironment (TME) may promote disease progression and lead to therapeutic resistance. Dr. Yang aims to uncover fundamental principles of tumor evolution by generating a comprehensive and quantitative "traffic map" of cancer cell state transitions and fitness changes during tumor development. Understanding this fundamental question has the potential to reveal key biomarkers that predict treatment response and actionable targets that drive resistance, thereby opening up new possibilities for long-lasting, multilayered tumor control.

Xiaoyu Zhang, PhD, Northwestern University, Evanston
"Discovery of chemical probes that support targeted protein degradation in human cancer"

Dr. Zhang is developing small molecules that promote targeted protein degradation in human cancers. Conventional small molecule anticancer drugs act by directly inhibiting the functions of proteins. Although targeted cancer therapies have been successful in recent years, many oncogenic proteins are still considered "undruggable" because the conventional drug design strategy fails to interfere with these proteins. One way to target "undruggable" oncogenic proteins may be to create a new type of small molecule that delivers these proteins to the cellular degradation system, thereby promoting their destruction. By integrating chemical tools, proteomic platforms, and molecular biology approaches, Dr. Zhang aims to develop protein degraders as a new drug modality to expand treatment opportunities in human cancer.

Xin Zhou, PhD, University of California, San Francisco
New position: Assistant Professor at Harvard Medical School/Dana-Farber Cancer Institute (starting 3/1/2022)
"Engineering next-generation methods to study and perturb protein post-translational modifications"

Antibodies, vaccines, checkpoint inhibitors, and CAR-T cells have all been successful in leveraging the immune system against disease, but these treatment strategies still have limitations. Dr. Zhou is designing new macromolecules to direct the immune response to cancer. She plans to engineer dynamic, functional proteins that respond to specific protein post-translational modifications, conformations, or complexes. She hypothesizes that these conditionally activated proteins will be able to recognize cancer-specific antigens, drive protein-protein or protein-substrate interactions, or help build synthetic cell signaling pathways, and therefore can be harnessed to enact specific anti-tumor responses.

November 2021 Damon Runyon Fellows:

Charles H. Adelmann, PhD, with his sponsor David E. Fisher, MD, PhD, at Massachusetts General Hospital, Boston

Skin cancer is the most common type of cancer worldwide, and sun exposure is known to be one of the main risk factors for developing skin cancers. Melanin pigment gives our hair, eyes, and skin their color, and it also shields skin cells from the carcinogenic effects of sun exposure. Combining just one enzyme (tyrosinase) and two substrates (oxygen and tyrosine) in the lab results in the generation of melanin-;yet we know that dozens of other proteins affect pigmentation in humans. How does a process that requires so few components in vitro utilize these other factors in the human body? Dr. Adelmann's work focuses on the cellular and biochemical contributors to human pigmentation, a clearer understanding of which will facilitate chemopreventative interventions for skin cancer that manipulate or mimic the anti-cancer properties of pigmentation. Dr. Adelmann received his PhD from Massachusetts Institute of Technology and his BA from Rice University.

Rico C. Ardy, PhD [Robert Black Fellow], with his sponsor Thomas Norman, PhD, at Memorial Sloan Kettering Cancer Center, New York

Dr. Ardy is investigating the genetic determinants that govern the behavior of fibroblasts, a type of connective tissue cell that has been implicated in arthritis, heart disease, and cancer. Activated fibroblasts can exacerbate disease through various mechanisms, including remodeling tissue architecture and modulating the immune system. Dr. Ardy plans on using state-of-the-art genetic tools, including CRISPR inhibition and activation coupled with single-cell RNA sequencing technology, to uncover the proteins and pathways that regulate fibroblast behavior and thereby inform the development of new targeted cancer treatments. Dr. Ardy received his PhD from the Medical University of Vienna and his BS from the University of California, Los Angeles.

Debadrita Bhattacharya, PhD [Robert Black Fellow], with her sponsor Julien Sage, PhD, at Stanford University School of Medicine, Stanford

Intra-tumoral heterogeneity (ITH), or the evolution of distinct cell types within a tumor, underlies most fatal features of cancer and presents a great therapeutic challenge. Using small cell lung cancer (SCLC), a highly heterogeneous and lethal form of lung cancer, as a model, Dr. Bhattacharya will study how ITH arises during cancer progression. She will employ emerging genomics techniques to characterize the cellular subtypes that comprise SCLC tumors and identify "druggable" transcription factors which, if targeted, could reduce tumor heterogeneity in this cancer. By profiling thousands of cells from treatment-naïve and therapy-resistant tumors, Dr. Bhattacharya aims to identify the "master-regulators" of the cellular subtypes that expand upon treatment in SCLC. She will then evaluate the role of these factors in human patient-derived cell lines, with the goal of uncovering novel mechanisms underlying ITH in human cancers. Dr. Bhattacharya received her PhD from Cornell University and her BS from the University of Calcutta.

Felix C. Boos, PhD, with his sponsor Anne Brunet, PhD, at Stanford University, Stanford

Evidence that aging is driven by defined, regulated processes (rather than simple "wear and tear") has sparked hope that we might target these processes to fight age-related diseases. A particularly exciting example is the regulation of protein homeostasis, or the balance between protein synthesis, folding, and degradation. Protein homeostasis is deregulated in both cancer and normal aging, but the underlying mechanisms remain elusive. Dr. Boos will use the short-lived African turquoise killifish as a new model organism to study how different cells and tissues respond to protein misfolding, how they coordinate their responses, and how aging influences these pathways. This research will not only unravel fundamental mechanisms of aging, but also inform new strategies to fight multiple types of cancer. Dr. Boos received his PhD and his B.Ed. from the University of Kaiserslautern.

Fangtao Chi, PhD, with his sponsor Ömer H. Yilmaz, MD, PhD, at Massachusetts Institute of Technology, Cambridge

Dietary interventions such as caloric restriction (CR) and ketogenic diet (KD) are reported to limit tumor growth partially by modulating stem cell function. The intestine functions as the main organ of nutrient absorption and, due to rapid tissue renewal via intestinal stem cells (ISCs), is sensitive to shifts in the body's metabolic state before and after eating. Both CR and KD conditions dramatically enhance the activity of an enzyme in ISCs known as HMGCS2. This enzyme controls ketogenesis, the conversion of fatty acids into ketone bodies as a means of producing energy when glucose is unavailable. Dr. Chi aims to dissect the role of ketone body metabolites in modulating intestinal stem cell function and tumor growth. With a better understanding of how intestinal stem cells adapt to diverse diets, he hopes to identify new strategies or dietary interventions that prevent and reduce the growth of cancers in the intestinal tract. Dr. Chi received his PhD from the University of California, Los Angeles and his BS from Zhejiang University.

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

Macrophages are specialized immune cells responsible for "eating" harmful cells, presenting antigens to T cells, and initiating inflammation by releasing signaling molecules called cytokines. Macrophages could potentially be activated to attack tumor cells, but for reasons that are currently unclear, they instead signal for the tumor to grow faster and become more invasive. Dr. Courvan is investigating how macrophages respond to the low-oxygen environment inside tumors, and specifically how they regulate gene expression through post-transcriptional mechanisms in low-oxygen conditions. With this research, he hopes to uncover new ways to leverage the body's immune system against cancerous cells. Dr. Courvan received his PhD from Yale University and his BS from the University of Connecticut.

Elizabeth R. Hughes, PhD [Robert Black Fellow], with her sponsor Raphael H. Valdivia, PhD, at Duke University School of Medicine, Durham

Immune checkpoint inhibitors, a type of cancer treatment that helps immune cells identify and kill tumor cells, have been a major breakthrough in the treatment of many cancer types. Unfortunately, not all patients respond to this immunotherapy. Dr. Hughes is studying how gut microbes improve response to immune checkpoint inhibitors. The bacterium Akkermansia muciniphila lives in the gastrointestinal tract and has been shown to improve response to immune checkpoint inhibitors via poorly understood mechanisms. Dr. Hughes aims to discover how A. muciniphila improves response to cancer immunotherapies and to design microbe-based therapeutic strategies that will further enhance cancer immunotherapy responses. Dr Hughes received her PhD from UT Southwestern Medical Center and her BS from Baylor University.

Henry R. Kilgore, PhD, with his sponsor Richard A. Young, PhD, at Whitehead Institute for Biomedical Research, Cambridge

Cells are compartmentalized into membrane-bound and membrane-less organelles, providing spatial structure to the cell's concentration of proteins and nucleic acids. Dr. Kilgore's research aims to understand the environment inside different organelles and apply this knowledge to the development of targeted cancer therapies, as better targeting within the cell will improve drug efficacy, increase potency, and decrease side effects. Using both live cells and reductionist models, he will investigate how molecules distribute themselves within the cell as a function of their chemical properties. Learning and applying the chemical grammar of this spatial partitioning will enable the design and preparation of molecular probes and drugs that synergize with the chemistry of the cell as a mechanism of treating all cancers. Dr. Kilgore received his PhD from Massachusetts Institute of Technology and his BS from the University of California, Berkeley.

Siqi Li, PhD [The Mark Foundation for Cancer Research Fellow], with her sponsor Slobodan Beronja, PhD, at Fred Hutchinson Cancer Research Center, Seattle

Dr. Li studies signaling events regulating the competition between cells carrying cancer-causing mutations and normal cells during cancer initiation. Previous studies have shown that intercellular signaling between mutant and normal cells could regulate the proliferation of these cells and shape the outcome of cancer initiation. Dr. Li is adapting novel tools to identify what molecular cues are mediating this crosstalk and how they contribute to cancer growth in mouse skin. Understanding these events may guide the development of cancer prevention strategies that restrict the early expansion of mutant cell lines in skin and other tissues. Dr. Li received her PhD from Duke University and her BS from Tsinghua University.

Ngoc-Han Tran, PhD, with her sponsor Ruth Lehmann, PhD, at Whitehead Institute for Biomedical Research, Cambridge

Cell division is often described in terms of the inheritance of DNA. An equally important but less understood task of cell division is the distribution of cellular machineries responsible for decoding the genome. Dr. Tran studies how the cell's major protein manufacturing factory, the endoplasmic reticulum (ER), is passed down through the germ cells that give rise to sperm and eggs. She is investigating whether ER inheritance plays a role in endowing germ cells with their unique properties, such as immortality and the ability to generate a new organism. Cancer cells, more so than their healthy neighbors, are highly dependent on the ER to produce building blocks to fuel their rapid growth. They also frequently tweak ER quality control mechanisms to avoid programmed cell death, typically triggered in cells experiencing persistent ER stress. Because the ER plays diverse roles in healthy cells and is frequently dysregulated in cancer, Dr. Tran's efforts to understand basic ER biology and its inheritance within germ cells will contribute to the collective efforts to treat this heterogeneous disease. Dr. Tran received her PhD from the University of California, San Francisco and her BS from San Jose State University.

Catherine Triandafillou, PhD, with her sponsor Daniel F. Jarosz, PhD, at Stanford University School of Medicine, Stanford

One of the tools cancer cells employ to evade immune system detection is an increased DNA mutation rate, with some cancers mutating 100-1000 times faster than healthy tissue. Classic studies of the effects of mutations predict that most genetic changes are deleterious, yet high mutation rates appear to help cancer cells adapt and invade. Dr. Triandafillou will address this paradox by using a single-cell model of cancer to measure the effects of mutations with much greater accuracy and resolution than is possible in live cancer cells. This information will help us understand how cancer cells balance deleterious mutations with the ability to adapt, and how the effects of mutations interact. She will also perform laboratory evolution experiments to track the adaptive process in different environmental conditions, mimicking the process by which cancer cells are able to colonize new micro-environments within tumors and throughout the body. This work will provide a clearer picture of how cancer cells use new mutations to proliferate. Dr. Triandafillou received her PhD from the University of Chicago and her BS from Temple University.

Patrick J. Woida, PhD, with his sponsor Rebecca Lamason, PhD, at Massachusetts Institute of Technology, Cambridge

Dr. Woida studies the foodborne pathogens Listeria monocytogenes and Shigella flexneri that enter and replicate within human cells. These bacteria also directly infect neighboring cells by pushing against the host cell membrane to form long membrane protrusions that extend and eventually release the bacteria into the new cell. This process of cell-to-cell spread requires the bacteria to hijack intercellular signaling pathways to reshape the host cell membrane. These signaling pathways normally regulate human cell adhesion and motility, and their dysregulation promotes tumor growth and metastasis. Dr. Woida's goal is to uncover the unique mechanisms by which these pathogens remodel the host cell membrane to gain insight into how the co-opted intercellular signaling pathways function under both healthy conditions and tumor progression. Dr. Woida received his PhD from Northwestern University and his BS from the University of Illinois at Urbana-Champaign.

Zeda Zhang, PhD [HHMI Fellow], with his sponsor Scott W. Lowe, PhD, at Memorial Sloan Kettering Cancer Center, New York

On the cellular level, aging manifests as cellular senescence-;when cells permanently stop multiplying but do not die. Aberrant accumulation of senescent cells is thought to be a major contributor to age-dependent tissue degeneration and its associated pathologies. Elimination of senescent cells has been shown to improve age-associated tissue damage pathologies and extend healthy lifespan in mice. Senescent cells undergo extensive remodeling on their surface, including increased production of many surface proteins. Dr. Zhang is using a quantitative proteomics approach to investigate the mechanisms and biological consequences of cell surface remodeling in senescent cells. His goal is to identify new therapeutic targets on the senescent cell surface and develop next-generation chimeric antigen receptor (CAR) T cells and antibodies to evaluate their impact on age-related diseases. Success with this approach may have a transformative impact on treating life-threatening diseases like cancer, fibrosis, and atherosclerosis. Dr. Zhang received his PhD from Gerstner Sloan Kettering Graduate School and his BS from Sun Yat-Sen University.

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