The Damon Runyon Most cancers Analysis Basis has introduced its latest cohort of Damon Runyon Fellows, 13 excellent postdoctoral scientists conducting fundamental and translational most cancers analysis within the laboratories of main senior investigators. This prestigious, four-year Fellowship encourages the nation’s most promising younger scientists to pursue careers in most cancers analysis by offering them with impartial funding ($231,000 complete) to work on modern initiatives.
The Committee additionally chosen six new recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists. This award acknowledges Damon Runyon Fellows who’ve exceeded the Basis’s highest expectations and are most definitely to make paradigm-shifting breakthroughs that remodel the way in which we forestall, diagnose, and deal with most cancers. To catapult their analysis careers—and their impression—Damon Runyon makes an extra funding of $100,000 in these distinctive people.
“Being awarded the Dale F. Frey Breakthrough Scientist Award will permit me to take dangers that I in any other case wouldn’t have,” says Allison Didychuk, PhD. “That features increasing into new approaches for me, like single molecule biophysics and useful genomics—and buying important gear that has been held up by provide chain shortages!”
Be taught in regards to the new Fellows and Breakthrough Scientists beneath.
2022 Recipients of the Damon Runyon-Dale F. Frey Award for Breakthrough Scientists:
Robert S. Banh, PhD, New York College Grossman College of Medication, New York
“Codon- and nutrient-specific regulation of mRNA translation in pancreatic most cancers”
In response to nutrient modifications within the atmosphere, pancreatic most cancers cells can alter the speed of mRNA translation to selectively regulate the speed of protein manufacturing. Nonetheless, the precise codons—the trinucleotide sequences that correspond to particular amino acids—and regulatory mechanisms used should not identified. Dr. Banh’s analysis goals to decipher the legal guidelines governing how codons regulate mRNA translation in response to the nutrient atmosphere in pancreatic cancers. As most cancers cells have many codon-altering mutations and are consistently adapting to modifications within the nutrient atmosphere, these research will supply perception into tumor evolution and will uncover novel therapeutic methods for pancreatic and different most cancers sufferers.
Allison L. Didychuk, PhD, College of California, Berkeley
New place: Assistant Professor at Yale College (beginning 7/1/2022)
“Viral mimics of host transcription components in oncogenic herpesviruses”
Kaposi’s sarcoma herpesvirus (KSHV) is a human oncogenic virus and the causative agent of cancers together with Kaposi’s sarcoma, main effusion lymphoma, and Multicentric Castleman illness. The associated human herpesvirus Epstein-Barr Virus (EBV) is much more prevalent than KSHV, and is linked to cancers together with Burkitt’s lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma. Dr. Didychuk is investigating the mechanisms by which KSHV co-opts the mobile host equipment to provide its personal gene merchandise in a fashion distinct from different viruses and host cells. A molecular understanding of how herpesviruses hijack the late gene transcription equipment will reveal new therapeutic weaknesses within the viral lifecycle and permit for structure-guided design of novel anti-viral drug targets.
Christopher P. Lapointe, PhD, Stanford College, Stanford
“Basic mechanisms that underlie human translation initiation and its dysregulation in most cancers”
Dr. Lapointe research how the synthesis of proteins (translation) is managed, as dysregulated translation is a ubiquitous characteristic of most cancers. He’s targeted on a key query: how regulation that originates on the “tail” finish of a messenger RNA (mRNA) impacts the beginning of translation, which happens close to the start of the mRNA. His purpose is to disclose and analyze pathways that underlie this elementary mechanism to manage gene expression. Utilizing an built-in method of single-molecule fluorescence microscopy, structural, and biochemical methods, this analysis will yield essential insights into how translation is exactly regulated and the way it’s disrupted in a big selection of cancers.
Dian Yang, PhD, Whitehead Institute for Biomedical Analysis, Cambridge
“Dissecting intratumoral heterogeneity and hierarchy at single cell decision”
Dr. Yang is analyzing tumor heterogeneity in quest of new diagnostic markers and potential therapeutic targets. A tumor consists of not solely most cancers cells, but in addition immune cells, fibroblasts, and different stromal elements. The various cell varieties and cell states that type the tumor microenvironment (TME) could promote illness development and result in therapeutic resistance. Dr. Yang goals to uncover elementary rules of tumor evolution by producing a complete and quantitative “site visitors map” of most cancers cell state transitions and health modifications throughout tumor improvement. Understanding this elementary query has the potential to disclose key biomarkers that predict therapy response and actionable targets that drive resistance, thereby opening up new potentialities for long-lasting, multilayered tumor management.
Xiaoyu Zhang, PhD, Northwestern College, Evanston
“Discovery of chemical probes that assist focused protein degradation in human most cancers”
Dr. Zhang is creating small molecules that promote focused protein degradation in human cancers. Standard small molecule anticancer medication act by instantly inhibiting the capabilities of proteins. Though focused most cancers therapies have been profitable lately, many oncogenic proteins are nonetheless thought-about “undruggable” as a result of the standard drug design technique fails to intervene with these proteins. One option to goal “undruggable” oncogenic proteins could also be to create a brand new sort of small molecule that delivers these proteins to the mobile degradation system, thereby selling their destruction. By integrating chemical instruments, proteomic platforms, and molecular biology approaches, Dr. Zhang goals to develop protein degraders as a brand new drug modality to broaden therapy alternatives in human most cancers.
Xin Zhou, PhD, College of California, San Francisco
New place: Assistant Professor at Harvard Medical College/Dana-Farber Most cancers Institute (beginning 3/1/2022)
“Engineering next-generation strategies to check and perturb protein post-translational modifications”
Antibodies, vaccines, checkpoint inhibitors, and CAR-T cells have all been profitable in leveraging the immune system in opposition to illness, however these therapy methods nonetheless have limitations. Dr. Zhou is designing new macromolecules to direct the immune response to most cancers. She plans to engineer dynamic, useful proteins that reply to particular protein post-translational modifications, conformations, or complexes. She hypothesizes that these conditionally activated proteins will be capable to acknowledge cancer-specific antigens, drive protein-protein or protein-substrate interactions, or assist construct artificial cell signaling pathways, and due to this fact could be harnessed to enact particular anti-tumor responses.
November 2021 Damon Runyon Fellows:
Charles H. Adelmann, PhD, together with his sponsor David E. Fisher, MD, PhD, at Massachusetts Common Hospital, Boston
Pores and skin most cancers is the commonest sort of most cancers worldwide, and solar publicity is understood to be one of many important danger components for creating pores and skin cancers. Melanin pigment offers our hair, eyes, and pores and skin their shade, and it additionally shields pores and skin cells from the carcinogenic results of solar publicity. Combining only one enzyme (tyrosinase) and two substrates (oxygen and tyrosine) within the lab leads to the technology of melanin—but we all know that dozens of different proteins have an effect on pigmentation in people. How does a course of that requires so few elements in vitro make the most of these different components within the human physique? Dr. Adelmann’s work focuses on the mobile and biochemical contributors to human pigmentation, a clearer understanding of which can facilitate chemopreventative interventions for pores and skin most cancers that manipulate or mimic the anti-cancer properties of pigmentation. Dr. Adelmann obtained his PhD from Massachusetts Institute of Expertise and his BA from Rice College.
Rico C. Ardy, PhD [Robert Black Fellow], together with his sponsor Thomas Norman, PhD, at Memorial Sloan Kettering Most cancers Heart, New York
Dr. Ardy is investigating the genetic determinants that govern the conduct of fibroblasts, a kind of connective tissue cell that has been implicated in arthritis, coronary heart illness, and most cancers. Activated fibroblasts can exacerbate illness by varied mechanisms, together with transforming tissue structure and modulating the immune system. Dr. Ardy plans on utilizing state-of-the-art genetic instruments, together with CRISPR inhibition and activation coupled with single-cell RNA sequencing know-how, to uncover the proteins and pathways that regulate fibroblast conduct and thereby inform the event of recent focused most cancers therapies. Dr. Ardy obtained his PhD from the Medical College of Vienna and his BS from the College of California, Los Angeles.
Debadrita Bhattacharya, PhD [Robert Black Fellow], together with her sponsor Julien Sage, PhD, at Stanford College College of Medication, Stanford
Intra-tumoral heterogeneity (ITH), or the evolution of distinct cell varieties inside a tumor, underlies most deadly options of most cancers and presents an awesome therapeutic problem. Utilizing small cell lung most cancers (SCLC), a extremely heterogeneous and deadly type of lung most cancers, as a mannequin, Dr. Bhattacharya will research how ITH arises throughout most cancers development. She is going to make use of rising genomics methods to characterize the mobile subtypes that comprise SCLC tumors and determine “druggable” transcription components which, if focused, may scale back tumor heterogeneity on this most cancers. By profiling hundreds of cells from treatment-naïve and therapy-resistant tumors, Dr. Bhattacharya goals to determine the “master-regulators” of the mobile subtypes that broaden upon therapy in SCLC. She is going to then consider the position of those components in human patient-derived cell strains, with the purpose of uncovering novel mechanisms underlying ITH in human cancers. Dr. Bhattacharya obtained her PhD from Cornell College and her BS from the College of Calcutta.
Felix C. Boos, PhD, together with his sponsor Anne Brunet, PhD, at Stanford College, Stanford
Proof that growing old is pushed by outlined, regulated processes (quite than easy “put on and tear”) has sparked hope that we’d goal these processes to struggle age-related ailments. A very thrilling instance is the regulation of protein homeostasis, or the stability between protein synthesis, folding, and degradation. Protein homeostasis is deregulated in each most cancers and regular growing old, however the underlying mechanisms stay elusive. Dr. Boos will use the short-lived African turquoise killifish as a brand new mannequin organism to check how completely different cells and tissues reply to protein misfolding, how they coordinate their responses, and the way growing old influences these pathways. This analysis is not going to solely unravel elementary mechanisms of growing old, but in addition inform new methods to struggle a number of kinds of most cancers. Dr. Boos obtained his PhD and his B.Ed. from the College of Kaiserslautern.
Fangtao Chi, PhD, together with his sponsor Ömer H. Yilmaz, MD, PhD, at Massachusetts Institute of Expertise, Cambridge
Dietary interventions reminiscent of caloric restriction (CR) and ketogenic food regimen (KD) are reported to restrict tumor progress partially by modulating stem cell operate. The gut capabilities as the primary organ of nutrient absorption and, because of fast tissue renewal through intestinal stem cells (ISCs), is delicate to shifts within the physique’s metabolic state earlier than and after consuming. Each CR and KD circumstances dramatically improve the exercise of an enzyme in ISCs often known as HMGCS2. This enzyme controls ketogenesis, the conversion of fatty acids into ketone our bodies as a method of manufacturing vitality when glucose is unavailable. Dr. Chi goals to dissect the position of ketone physique metabolites in modulating intestinal stem cell operate and tumor progress. With a greater understanding of how intestinal stem cells adapt to numerous diets, he hopes to determine new methods or dietary interventions that forestall and scale back the expansion of cancers within the intestinal tract. Dr. Chi obtained his PhD from the College of California, Los Angeles and his BS from Zhejiang College.
Edward M. C. Courvan, PhD [HHMI Fellow], together with his sponsor Roy R. Parker, PhD, at College of Colorado, Boulder
Macrophages are specialised immune cells accountable for “consuming” dangerous cells, presenting antigens to T cells, and initiating irritation by releasing signaling molecules known as cytokines. Macrophages may doubtlessly be activated to assault tumor cells, however for causes which might be presently unclear, they as a substitute sign for the tumor to develop sooner and turn into extra invasive. Dr. Courvan is investigating how macrophages reply to the low-oxygen atmosphere inside tumors, and particularly how they regulate gene expression by post-transcriptional mechanisms in low-oxygen circumstances. With this analysis, he hopes to uncover new methods to leverage the physique’s immune system in opposition to cancerous cells. Dr. Courvan obtained his PhD from Yale College and his BS from the College of Connecticut.
Elizabeth R. Hughes, PhD [Robert Black Fellow], together with her sponsor Raphael H. Valdivia, PhD, at Duke College College of Medication, Durham
Immune checkpoint inhibitors, a kind of most cancers therapy that helps immune cells determine and kill tumor cells, have been a serious breakthrough within the therapy of many most cancers varieties. Sadly, not all sufferers reply to this immunotherapy. Dr. Hughes is finding out how intestine microbes enhance response to immune checkpoint inhibitors. The bacterium Akkermansia muciniphila lives within the gastrointestinal tract and has been proven to enhance response to immune checkpoint inhibitors through poorly understood mechanisms. Dr. Hughes goals to find how A. muciniphila improves response to most cancers immunotherapies and to design microbe-based therapeutic methods that may additional improve most cancers immunotherapy responses. Dr Hughes obtained her PhD from UT Southwestern Medical Heart and her BS from Baylor College.
Henry R. Kilgore, PhD, together with his sponsor Richard A. Younger, PhD, at Whitehead Institute for Biomedical Analysis, Cambridge
Cells are compartmentalized into membrane-bound and membrane-less organelles, offering spatial construction to the cell’s focus of proteins and nucleic acids. Dr. Kilgore’s analysis goals to grasp the atmosphere inside completely different organelles and apply this information to the event of focused most cancers therapies, as higher focusing on throughout the cell will enhance drug efficacy, enhance efficiency, and reduce negative effects. Utilizing each reside cells and reductionist fashions, he’ll examine how molecules distribute themselves throughout the cell as a operate of their chemical properties. Studying and making use of the chemical grammar of this spatial partitioning will allow the design and preparation of molecular probes and medicines that synergize with the chemistry of the cell as a mechanism of treating all cancers. Dr. Kilgore obtained his PhD from Massachusetts Institute of Expertise and his BS from the College of California, Berkeley.
Siqi Li, PhD [The Mark Foundation for Cancer Research Fellow], together with her sponsor Slobodan Beronja, PhD, at Fred Hutchinson Most cancers Analysis Heart, Seattle
Dr. Li research signaling occasions regulating the competitors between cells carrying cancer-causing mutations and regular cells throughout most cancers initiation. Earlier research have proven that intercellular signaling between mutant and regular cells may regulate the proliferation of those cells and form the result of most cancers initiation. Dr. Li is adapting novel instruments to determine what molecular cues are mediating this crosstalk and the way they contribute to most cancers progress in mouse pores and skin. Understanding these occasions could information the event of most cancers prevention methods that prohibit the early growth of mutant cell strains in pores and skin and different tissues. Dr. Li obtained her PhD from Duke College and her BS from Tsinghua College.
Ngoc-Han Tran, PhD, together with her sponsor Ruth Lehmann, PhD, at Whitehead Institute for Biomedical Analysis, Cambridge
Cell division is commonly described by way of the inheritance of DNA. An equally essential however much less understood process of cell division is the distribution of mobile machineries accountable for decoding the genome. Dr. Tran research how the cell’s main protein manufacturing manufacturing unit, the endoplasmic reticulum (ER), is handed down by the germ cells that give rise to sperm and eggs. She is investigating whether or not ER inheritance performs a job in endowing germ cells with their distinctive properties, reminiscent of immortality and the power to generate a brand new organism. Most cancers cells, extra so than their wholesome neighbors, are extremely depending on the ER to provide constructing blocks to gasoline their fast progress. In addition they steadily tweak ER high quality management mechanisms to keep away from programmed cell dying, sometimes triggered in cells experiencing persistent ER stress. As a result of the ER performs numerous roles in wholesome cells and is steadily dysregulated in most cancers, Dr. Tran’s efforts to grasp fundamental ER biology and its inheritance inside germ cells will contribute to the collective efforts to deal with this heterogeneous illness. Dr. Tran obtained her PhD from the College of California, San Francisco and her BS from San Jose State College.
Catherine Triandafillou, PhD, together with her sponsor Daniel F. Jarosz, PhD, at Stanford College College of Medication, Stanford
One of many instruments most cancers cells make use of to evade immune system detection is an elevated DNA mutation fee, with some cancers mutating 100-1000 instances sooner than wholesome tissue. Traditional research of the consequences of mutations predict that the majority genetic modifications are deleterious, but excessive mutation charges seem to assist most cancers cells adapt and invade. Dr. Triandafillou will handle this paradox by utilizing a single-cell mannequin of most cancers to measure the consequences of mutations with a lot larger accuracy and determination than is feasible in reside most cancers cells. This data will assist us perceive how most cancers cells stability deleterious mutations with the power to adapt, and the way the consequences of mutations work together. She can even carry out laboratory evolution experiments to trace the adaptive course of in several environmental circumstances, mimicking the method by which most cancers cells are in a position to colonize new micro-environments inside tumors and all through the physique. This work will present a clearer image of how most cancers cells use new mutations to proliferate. Dr. Triandafillou obtained her PhD from the College of Chicago and her BS from Temple College.
Patrick J. Woida, PhD, together with his sponsor Rebecca Lamason, PhD, at Massachusetts Institute of Expertise, Cambridge
Dr. Woida research the foodborne pathogens Listeria monocytogenes and Shigella flexneri that enter and replicate inside human cells. These micro organism additionally instantly infect neighboring cells by pushing in opposition to the host cell membrane to type lengthy membrane protrusions that stretch and ultimately launch the micro organism into the brand new cell. This means of cell-to-cell unfold requires the micro organism to hijack intercellular signaling pathways to reshape the host cell membrane. These signaling pathways usually regulate human cell adhesion and motility, and their dysregulation promotes tumor progress and metastasis. Dr. Woida’s purpose is to uncover the distinctive mechanisms by which these pathogens rework the host cell membrane to achieve perception into how the co-opted intercellular signaling pathways operate beneath each wholesome circumstances and tumor development. Dr. Woida obtained his PhD from Northwestern College and his BS from the College of Illinois at Urbana-Champaign.
Zeda Zhang, PhD [HHMI Fellow], together with his sponsor Scott W. Lowe, PhD, at Memorial Sloan Kettering Most cancers Heart, New York
On the mobile degree, growing old manifests as mobile senescence—when cells completely cease multiplying however don’t die. Aberrant accumulation of senescent cells is considered a serious contributor to age-dependent tissue degeneration and its related pathologies. Elimination of senescent cells has been proven to enhance age-associated tissue injury pathologies and lengthen wholesome lifespan in mice. Senescent cells endure in depth transforming on their floor, together with elevated manufacturing of many floor proteins. Dr. Zhang is utilizing a quantitative proteomics method to analyze the mechanisms and organic penalties of cell floor transforming in senescent cells. His purpose is to determine new therapeutic targets on the senescent cell floor and develop next-generation chimeric antigen receptor (CAR) T cells and antibodies to judge their impression on age-related ailments. Success with this method could have a transformative impression on treating life-threatening ailments like most cancers, fibrosis, and atherosclerosis. Dr. Zhang obtained his PhD from Gerstner Sloan Kettering Graduate College and his BS from Solar Yat-Sen College.
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Concerning the Damon Runyon Most cancers Analysis Basis
To speed up breakthroughs, the Damon Runyon Most cancers Analysis Basis supplies at present’s greatest younger scientists with funding to pursue modern analysis. The Basis has gained worldwide prominence in most cancers analysis by figuring out excellent researchers and physician-scientists. 13 scientists supported by the Basis have obtained the Nobel Prize, and others are heads of most cancers facilities and leaders of famend analysis packages. Every of its award packages is extraordinarily aggressive, with lower than 10% of functions funded. Since our founding in 1946, in partnership with donors throughout the nation, the Damon Runyon Most cancers Analysis Basis has invested almost $420 million and funded over 3,900 scientists. Final 12 months, it dedicated over $18 million in new awards to sensible younger investigators.
100% of all donations to the Basis are used to assist scientific analysis. Administrative and fundraising prices are paid with income from the Damon Runyon Broadway Tickets Service and our endowment.
For extra data go to damonrunyon.org.
