Dr. Otten [HHMI Fellow] is investigating the catalytic mechanism of protein kinases, an important family of proteins that are present in bacteria, plants and humans. These proteins play a central role in signal transduction pathways and orchestrating the cell cycle; aberrant activity, however, has been shown to cause certain human cancers. A firm grasp of their mechanism is thus of great interest, from a fundamental point of view and also because it holds promise for the development of new therapeutics.

Project Title: "Mechanism of kinases at atomic resolution"

Institution: Brandeis University

Sponsor(s) / Mentor(s): Dorothee Kern, PhD

Cancer Type: All cancers

Research Area: Biophysics

Dr. Sweeney [HHMI Fellow] is using the frog as a model to study how neurons diversify in the spinal cord as limbs develop and a swimming tadpole becomes a hopping frog. Many different types of nerve cells, each with their own unique characteristics, make up the healthy nervous system. Understanding how a cell’s fate is specified will provide the basis for understanding how cancer reprograms a cell.

Project Title: "Spinal circuit remodeling during developmental transitions in motor behavioral strategy"

Institution: The Salk Institute for Biological Studies

Sponsor(s) / Mentor(s): Christopher R. Kintner, PhD, and Thomas M. Jessell, PhD

Cancer Type: All cancers

Research Area: Developmental Neurobiology

Dr. Hall [Dale F. and Betty Ann Frey Fellow] is investigating the biochemical and metabolic pathways that regulate the activity of the protein RORγ/γt, which has crucial importance in metabolism and immune system homeostasis. It is also linked to the development of chronic inflammation, a known trigger and promoter of certain tumor types. Understanding the regulation of RORγ/γt will facilitate the development of new therapeutics to manage chronic inflammatory disease and prevent tumorigenesis.

Project Title: "Regulation of the ligand for retinoic acid receptor related orphan receptor gamma t"

Institution: New York University School of Medicine

Sponsor(s) / Mentor(s): Dan R. Littman, MD, PhD

Cancer Type: Colorectal

Research Area: Basic Immunology

Dr. Kleiner is studying proteins called microtubules, which play a crucial role in the maintenance and proliferation of cancer cells. Microtubules form the cytoskeleton (the cellular “scaffold”), and their function is regulated, in part, by chemical modifications or “flags” on the microtubule proteins. He aims to combine chemical, biochemical and biophysical approaches to better explain the role of these modifications on cell physiology and drug sensitivity. These studies will enable the identification of novel strategies for improving the efficacy of existing microtubule-targeted cancer drugs.

Project Title: "Investigating the importance of post-translational microtubule modification using recombinant acetylated tubulin"

Institution: The Rockefeller University

Sponsor(s) / Mentor(s): Tarun M. Kapoor, PhD

Cancer Type: All cancers

Research Area: Chemical Biology

Dr. McGinty is examining the structure and function of enzymes called methyltransferases. As these enzymes are commonly misregulated in human leukemias, an understanding of their normal function may provide insight into novel platforms for drug development.

Project Title: "Structural studies of the MLL1 core methyltransferase complex"

Institution: Pennsylvania State University

Sponsor(s) / Mentor(s): Song Tan, PhD

Cancer Type: Leukemias

Research Area: Chromatin Biology

Dr. Moravcevic [HHMI Fellow] is studying sleep deprivation, which leads to an increased risk of several diseases including cancer. Little is currently known about the function of sleep or about the molecular mechanisms that control the need to sleep. To begin to understand why sleep deprivation has such a negative impact on human health, she will address how and why the need to sleep builds up after prolonged wakefulness. She will use fruit flies as a model system to determine the genetic and molecular basis of sleep homeostasis.

Project Title: "Investigating the genetic and neurochemical basis of sleep homeostasis"

Institution: University of Pennsylvania School of Medicine

Sponsor(s) / Mentor(s): Amita Sehgal, PhD

Cancer Type: Breast, Colorectal

Research Area: Basic Genetics

Tumor-associated immune cells called macrophages are a key component of the tumor microenvironment and often portend a poor prognosis.  Macrophages are critical regulators of tumor angiogenesis and metastasis.  Interestingly, the function of macrophages is dependent on their surrounding microenvironment such that under certain conditions, macrophages can actually become tumor-suppressive.  The central hypothesis of Dr. Beatty’s work is that macrophages are an important yet pliable factor in tumor behavior, which can be therapeutically targeted and instructed to attack tumors and inhibit tumor growth.

Dr. Beatty [Nadia's Gift Foundation Innovator] will evaluate strategies to engineer macrophages to attack tumors and to resist signals produced within tumors that ordinarily prime macrophages with tumor-promoting properties.  He aims to combine these macrophage-directed approaches with standard chemotherapy.  The priority is to develop the necessary data to facilitate the rapid translation of this strategic approach to the clinic for treatment of patients with pancreatic cancer and other malignancies.

Project Title: "Targeting macrophages for cancer therapy"

Institution: University of Pennsylvania

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Immunotherapy

Dr. Chen aims to understand the relationship between small RNAs and cancer. Small RNAs are important regulators of genetic networks inside the cell; perturbation of these networks can lead to malignant cell growth. His goal is to develop anti-cancer drugs and therapies by targeting the process of small RNA production.

Project Title: "Investigation of Dicer as a novel therapeutic route towards the inhibition of tumorigenesis and neoplastic growth"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): Phillip A. Sharp, PhD

Cancer Type: Sarcomas

Research Area: Cancer Genetics

Dr. Yue is investigating the role of Leptin receptor signaling in blood stem cells (hematopoietic stem cells, HSCs). Leptin signals the nutritional status of the body and tightly controls energy metabolism and body weight. Interestingly, bone marrow stromal cells surrounding HSCs express very high levels of Leptin receptor; it is therefore possible that HSCs, which can initiate leukemia in pathological conditions, are regulated by nutritional changes in the microenvironment through Leptin signaling. These studies may enable successful HSC expansion and transplantation after chemotherapy in leukemia patients, and may also help prevent or treat other types of cancer.

Project Title: "Functional analysis of leptin receptor signaling in hematopoietic stem cells and perivascular niche"

Institution: University of Texas Southwestern Medical School

Sponsor(s) / Mentor(s): Sean J. Morrison, PhD

Cancer Type: Leukemias

Research Area: Stem Cell Biology

Dr. Wang [Robert Black Fellow] is studying Bacteroides fragilis, a common human gut bacterium that protects against inflammatory bowel diseases (IBD) in experimental models. This project will explore the mechanisms that contribute to bacterial colonization and long‐term maintenance in the gut. By combining bioinformatics, molecular genetics, protein biochemistry and innovative animal disease models, she hopes to better understand host‐microbe and microbe‐microbe interactions in the complex mammalian gut environment, and to potentially utilize B. fragilis as a preventative and therapeutic against IBD and/or colon cancer.

Project Title: "Diversity generating retroelement-mediated surface-protein display in Bacteroides fragilis and its roles in host-microbe interactions"

Institution: University of California, Los Angeles

Sponsor(s) / Mentor(s): Jeffery F. Miller, PhD

Cancer Type: Colorectal

Research Area: Microbiology

Dr. Skene is studying the mechanisms underlying how cells maintain a specific gene expression profile unique to that cell type. While current technologies allow the reprogramming of differentiated cells into stem cells, the therapeutic use of this technology is limited because not all cellular memory is erased. He aims to improve the reprogramming process by removing proteins responsible for cellular memory, thus generating stem cells with enhanced therapeutic properties. Stem cells have great potential in regenerative medicine, such as in renewing bone marrow following chemotherapy during cancer treatment.

Project Title: "Transcriptional memory in iPS cells: suppression of H3.3 deposition to increase therapeutic potential"

Institution: Fred Hutchinson Cancer Research Center

Sponsor(s) / Mentor(s): Mark T. Groudine, MD, PhD, and Steven Henikoff, PhD

Cancer Type: All cancers, Leukemias, Lymphomas, Myeloma

Research Area: Stem Cell Biology

Dr. Carroll aims to design small molecule inhibitor drugs with high affinity for the protein Vav1. This protein is an attractive target for treating pancreatic cancer because it is highly expressed in pancreatic adenocarcinomas and activates pro-cancer signaling. If she is successful, the resultant inhibitors of Vav1 will be useful as lead compounds to treat pancreatic cancer and also as chemical probes to examine the importance of Vav1 in signal transduction and human disease.

Project Title: "Validation of Vav1 as a druggable cancer target using small molecules"

Institution: Vanderbilt University Medical Center

Sponsor(s) / Mentor(s): Stephen W. Fesik, PhD

Cancer Type: Pancreatic

Research Area: Structural Biology

Dr. Sabin is studying the role of long noncoding RNAs (lncRNAs) in blood cell development. Although the precise function of most lncRNAs remains unclear, certain lncRNAs are involved in regulating gene expression and may therefore be important for proper blood cell maturation. Since several types of cancers arise from blood cell progenitors, understanding how lncRNAs function in these cells may provide novel diagnostic and therapeutic targets.

Project Title: "The role of long noncoding RNAs in normal hematopoiesis and malignant transformation"

Institution: Cold Spring Harbor Laboratory

Sponsor(s) / Mentor(s): Gregory J. Hannon, PhD

Cancer Type: Leukemias, Lymphomas

Research Area: Epigenetics

Dr. Matsuoka is investigating how the nervous and vascular systems cooperate to establish precise patterns of networks. Neuronal and vascular networks are fundamental for normal tissue function and homeostasis, and abnormalities in these networks lead to tissue dysfunction and diseases, including cancer. Understanding the molecular mechanisms that ensure accurate network formation is important to protect the body from various diseases.

Project Title: "Neurovascular interplay during the development and regeneration of the neuronal and vascular networks"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Didier Y.R. Stainier, PhD

Cancer Type: All cancers

Research Area: Developmental Biology

Dr. Phanstiel is studying transcription factors (TF), proteins that bind to DNA and regulate gene expression. Certain TFs have well-established roles in cancer and other diseases. He is using chromatin immunopreciptation combined with high-throughput sequencing (ChIP-Seq) to map TF-DNA binding sites in a variety of yeast strains. This research is expected to be important for understanding the mechanisms controlling gene expression in humans and their variation across populations, thus providing insights into cancer and other diseases.

Project Title: "Variation of transcription factor binding"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): Michael P. Snyder, PhD

Cancer Type: All cancers

Research Area: Genomics

Dr. Popp [HHMI Fellow] is focusing on the quality control mechanisms that cells utilize at the RNA level to ensure proper gene expression. Cells inspect and destroy aberrant mRNA messages using decay pathways; dysregulation of these RNA decay systems is implicated in various cancers. He will apply a new genetic screening method to identify components of RNA decay pathways and learn more about their role in cancer.

Project Title: "A haploid genetic approach towards defining RNA decay mechanisms in mammalian cells"

Institution: University of Rochester School of Medicine and Dentistry

Sponsor(s) / Mentor(s): Lynne E. Maquat, PhD

Cancer Type: All cancers

Research Area: RNA

Dr. Karijolich aims to define mechanisms involved in the regulation of gene expression, using a combination of biochemical and genetic approaches. An understanding of these mechanisms is key to understanding the development of cancer, and may potentially lead to novel cancer therapeutics.

Project Title: "Mechanistic and physiological analysis of transcription-dependent gene loops"

Institution: UMDNJ-Robert Wood Johnson Medical School

Sponsor(s) / Mentor(s): Michael Hampsey, PhD

Cancer Type: All cancers

Research Area: Biochemistry

Understanding proteins dysregulated in cancer is a vital step toward the discovery of effective targets for treatment.  Many cellular enzymes demonstrate aberrant activity in cancer, and a significant subset of them contain cysteine amino acid residues required for their function. 

Dr. Weerapana aims to use sophisticated chemical genetic approaches to develop novel small molecules that selectively target these cysteines, thus blocking protein function.  Her goal is to create a “chemical library” of these small molecules and use this library to identify compounds that affect cancer cell proliferation, migration and invasion in breast and ovarian cancer cell lines.  The cellular protein targets of these molecules will be identified, followed by analysis of their roles in cancer development and progression.  This multidisciplinary approach, encompassing aspects of synthetic chemistry, cell biology and proteomics, will identify new therapeutic targets and small molecule drug candidates for the diagnosis and treatment of cancer.

Project Title: "Targeting reactive cysteine residues for cancer therapy"

Institution: Boston College

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Chemical Biology

Recent genome sequencing studies have identified a large set of candidate genetic mutations implicated in a diverse range of cancer types.  However, in order to determine the causal role of each mutation in disease risk and pathology, researchers must be able to test each mutation individually in cellular or animal models.  This is severely limited by the difficulty of manipulating the genome of cells and organisms with precise control so that a specific disease can be definitively linked to single changes in the genome.

To address this challenge, Dr. Zhang proposes to engineer a comprehensive set of novel molecular tools to enable targeted modification of the mammalian genome.  He will demonstrate the power of these tools by testing genetic mutations associated with neuroblastoma and glioma brain tumors.  The development and application of these tools will establish a powerful new platform for investigating the underlying genetic and molecular mechanisms of cancer and will inform drug development.  To ensure maximal benefit and impact for the cancer community and beyond, he will also facilitate teaching and rapid open-source distribution of all tools developed.

Project Title: "Development and application of genome and epigenome engineering tools for cancer research"

Institution: The Broad Institute of MIT and Harvard

Sponsor(s) / Mentor(s): n/a

Cancer Type: Brain, Neuro-oncology

Research Area: Biomedical Engineering

Most early detection strategies for cancer focus on identifying protein biomarkers or “molecular signatures” of disease.  However, discovery of new biomarkers has lagged, due in large part to the inability to efficiently sift through complex cellular protein mixtures.  As a result, the number of new FDA-approved biomarker tests has declined over the last decade, and the current rate of biomarker validation is only one per year.

As proteins can be very large, they are typically cleaved into smaller units called peptides for identification and analysis.  The current technology for peptide identification is very slow and lacks the sensitivity and specificity required to quantify proteins in complex samples.  Dr. Hesselberth proposes that a massive acceleration in the rate of peptide sequencing would significantly impact biomarker research.  To accomplish this, he seeks to develop a highly parallel peptide sequencing platform with single molecule resolution that is orders of magnitude faster than existing technology.  This new approach would transform our capability to identify protein and peptide biomarkers for use in the early detection of cancer.

Project Title: "Peptide identification by massively-parallel sequencing"

Institution: University of Colorado Denver

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Proteomics

Cellular proteins are often modified with a “flag” that affects their function.  One such modification is the monosaccharide N-acetyl-glucosamine (O-GlcNAc), which is required for normal development and proper regulation of many biological pathways.  During metabolism, elevated glucose levels result in elevated O-GlcNAc modification of proteins. 

One common feature of all cancers is an altered metabolism that helps to protect cancer cells from the challenging environments they encounter during tumorigenesis and metastasis.  Dr. Pratt has uncovered a link between this change in metabolism and O-GlcNAc modification of proteins, which directly contributes to the proliferation and survival of cancer cells.  He seeks to understand the details of this link and exactly how it contributes to disease.  This approach will lead to a more complete understanding of how metabolism promotes cancer and may uncover new opportunities for treatment.

Project Title: "O-GIcNAc as a "sweet" link between metabolism and survival in cancer"

Institution: University of Southern California

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Chemical Biology

Dr. Valastyan [Harry Kriegel Fellow] seeks to uncover novel regulators of breast cancer metastasis. He has devised a novel experimental system that is capable of defining and exploiting the phenotypic heterogeneity and genetic diversity that exists within tumor cell populations. He anticipates that these studies will provide insights that further our comprehension of metastatic progression and suggest novel targets for the diagnosis and/or treatment of human breast cancer.

Project Title: "A novel system for the unbiased discovery of genes that regulate breast cancer metastasis"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Joan S. Brugge, PhD

Cancer Type: Breast

Research Area: Invasion and Metastasis

Dr. Trapnell studies the role of long noncoding RNAs (lncRNAs) in cancer. When tissue is damaged (e.g. by radiation or carcinogens), this class of genes may cause cancer or make it more difficult to treat. Using software and mathematics that he has developed for the analysis of massive-scale sequencing data, he aims to discover which genes are misregulated by lncRNA in tumor cells. This research may lead to the discovery of lncRNAs that could be targeted to halt cancer progression.

Project Title: "Globally characterizing lncRNA oncogenes with next-generation transcriptomics"

Institution: Harvard University

Sponsor(s) / Mentor(s): John L. Rinn, PhD

Cancer Type: All cancers

Research Area: RNA

Dr. Ward [HHMI Fellow] is studying key genetic pathways that may play a role in development of neurons in the Drosophila olfactory system. Many of the genes in these pathways are also involved in cancer. Correct neuronal wiring in this system requires precise targeting of neuronal outgrowths (axons and dendrites); this targeting depends largely on cell-cell interactions mediated by cell surface molecules. The ultimate goal of this research is to identify the upstream cell surface effectors of these pathways, thus providing further insight into cancer signaling.

Project Title: "Investigations of cancer signaling pathways in Drosophila olfactory system development"

Institution: Stanford University

Sponsor(s) / Mentor(s): Liqun Luo, PhD

Cancer Type: All cancers

Research Area: Developmental Neurobiology

Dr. Ewald [Dennis and Marsha Dammerman Fellow] studies the relationship between the parasite Toxoplasma gondii and the host cell. Nearly every cell in the body is equipped with sensors to survey itself for evidence of infection. Once triggered, these sensors often lead to cell suicide and the recruitment of immune cells to control the infection. She hopes to identify novel pathogen sensors that can be exploited to develop selective anti-tumor therapies.

Project Title: "Innate immune detection of Toxoplasma gondii in the host cell cytosol"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): John C. Boothroyd, PhD

Cancer Type: All cancers

Research Area: Infectious Disease

Dr. Youk [HHMI Fellow] aims to use quantitative models and experiments in yeast to unravel the central principles that enable cells to adhere to and communicate with each other in multicellular clusters. He is also investigating general strategies that these cells use to collectively process information and respond to biochemical signals that are present outside the cluster. These studies will lead to a better understanding of how multicellular clusters, such as tumors, develop and are maintained.

Project Title: "Synthetic development: Elucidating principles for genetically encoding simple multicellular architectures using Saccharomyces cerevisiae as a model system"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Wendell A. Lim, PhD

Cancer Type: All cancers

Research Area: Microbiology

Dr. de la Zerda is developing imaging technology to visualize and monitor changes in living cells. Cancer cells display unique sugar patterns on their surface, which contain tremendous diagnostic information about tumor aggressiveness and responsiveness to therapy. The initial goal is to use this imaging technology to monitor tumor sugar patterns, as a method to stratify patients with prostate cancer and determine which patients may benefit from treatment vs. “active surveillance.” In the future, this technology may be applied to other cancer types and may also shed light on the role of sugars in cancer development.

Project Title: "Imaging cancer glycomes with functionalized carbon nanotubes"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Carolyn R. Bertozzi, PhD

Cancer Type: Prostate

Research Area: Imaging

Dr. Huang is investigating the mechanism of how an ion channel protein promotes brain tumor growth. He hypothesizes that medulloblastoma, the most common pediatric brain cancer, utilizes a specific ion channel for its uncontrolled growth and metastasis. By exploring the functional roles of the ion channel in medulloblastoma, his goal is to identify new prognostic markers for tumor diagnosis and potentially develop novel cancer therapies.

Project Title: "Functional significance of potassium channel EAG2 in medulloblastoma"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Lily Y. Jan, PhD

Cancer Type: Neuro-oncology

Research Area: Animal Models/Mouse Models

Dr. Sarin [Marion Abbe Fellow] is studying how neurons use unique molecules on their cell surface to recognize one another during development. Such recognition is critical in ensuring appropriate spatial patterning and normal organ formation. A hallmark of cancerous cells is the inappropriate reactivation of cell migration, and the disruption of these patterns.

Project Title: "A molecular mechanism of spatial pattern formation in the vertebrate retina"

Institution: Harvard University

Sponsor(s) / Mentor(s): Joshua R. Sanes, PhD

Cancer Type: All cancers

Research Area: Neuroscience

Dr. Lu [Merck Fellow] is investigating the process of how cells interact with their surrounding microenvironment, specifically in the context of the regenerative response triggered by injury. She aims to better understand the underlying mechanisms of regeneration and how they influence the initiation and growth of malignant tumors.

Project Title: "The role of injury-inducible epithelial/stromal feedback signaling pathways in bladder cancer"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): Philip A. Beachy, PhD

Cancer Type: Bladder

Research Area: Signal Transduction

Dr. Jan [Rebecca Ridley Kry Fellow] is developing novel methods to examine the spatial control of gene expression within the cell. During gene expression, mRNAs are translated into proteins at different locations in the cell, which determines cell shape and behavior. Spatially localized mRNA translation influences cell adhesion and migration, both of which are disrupted in cancer—particularly during metastasis.

Project Title: "Studying translation with subcellular resolution"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Jonathan S. Weissman, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Righini [Merck Fellow] aims to characterize the dynamics of protein synthesis (translation). His research will permit a deeper understanding of this process and will provide insight on how it can be controlled. He will build a detailed model of translation, which may suggest new strategies for cancer therapy.

Project Title: "Single molecule translation control"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Carlos Bustamante, PhD

Cancer Type: All cancers

Research Area: Biophysics

Dr. Shibata [HHMI Fellow] focuses on specialized protein quality control (QC) mechanisms in the cell, which ensure the proper folding of new proteins and the disposal of mature ones that no longer perform their duties adequately. Protein QC in the cell nucleus likely plays a pivotal role in protecting the integrity of the genome, but very little is known about this pathway. She aims to identify the network of components that make up the nuclear protein QC system. Cancer cells rely on protein QC pathways to proliferate uncontrollably, and the identification of the QC components may provide new therapeutic targets against cancer.

Project Title: "Identifying protein quality control mechanisms in the nucleus"

Institution: Northwestern University

Sponsor(s) / Mentor(s): Richard I. Morimoto, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Simsek [Philip O’Bryan Montgomery, Jr., MD Fellow] is studying the role of ubiquitin protein signals in the maintenance of genome integrity. Since components of the ubiquitin system are often highly conserved from yeast to humans, yeast is ideally suited for the study of this complex process using a combination of functional genomics and biochemistry. The insights gained from the proposed studies may identify additional targets to combat cancer.

Project Title: "Understanding the physiological relevance of distinct polyubiquitin chains in the maintenance of genome integrity"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): David P. Toczyski, PhD

Cancer Type: All cancers

Research Area: Chromosome and Telomere Biology

Dr. Lu [Jake Wetchler Foundation Fellow for Pediatric Innovation] aims to develop antibody-drug conjugates (ADCs) that can specifically recognize and kill acute myeloid leukemia (AML) cancer cells. His goal is to generate highly specific ADCs that will attack tumor cells without having harmful effects on normal cells. This work may identify new clinical candidate drugs with optimized efficacy.

Project Title: "Homogeneous antibody-drug conjugates containing unnatural amino acid for targeted AML therapy"

Institution: The Scripps Research Institute

Sponsor(s) / Mentor(s): Peter G. Schultz, PhD

Cancer Type: Leukemias

Research Area: Biomedical Engineering

Dr. Chan [HHMI Fellow] is focusing on how cells slow their growth rate in response to stress. He aims to understand how stress signals are relayed to the cellular machinery that directs cell growth. Because tumor cells are constantly under stress yet display unregulated growth, it is critical to understand how stress signaling and growth control are coordinated. This research may lead to new understanding of how a broad range of cancers can be therapeutically targeted.

Project Title: "Determining the mechanism of stress-induced ribosomal protein mRNA degradation"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Karsten Weis, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Breslow [Connie and Bob Lurie Fellow] is studying the primary cilium, a cellular structure that enables cells to sense and respond to specific external cues. While disruptions to primary cilia are known to promote tumor formation and cause developmental defects, how cilia orchestrate these processes remains poorly understood. He is using a combination of genetic, biochemical and imaging approaches to investigate how lipid molecules contribute to the unique functions of cilia.

Project Title: "Dissecting the functions of phosphoinositide lipids in the primary cilium"

Institution: Stanford University

Sponsor(s) / Mentor(s): Maxence V. Nachury, PhD

Cancer Type: Brain, Neuro-oncology, Kidney, Pancreatic, Skin

Research Area: Cell Biology

Dr. Batista [Kenneth G. and Elaine A. Langone Fellow] is investigating the molecular mechanism by which long noncoding RNAs regulate gene expression. Long noncoding RNAs form a vital link between the information encoded in the genome and the instructions recorded at the structural chromatin level, thus maintaining cell identity. Understanding how long noncoding RNAs regulate gene expression will allow the development of powerful tools for diagnosis and treatment of cancer.

Project Title: "LincRNA dependent transcriptional memory in cancer stem cells"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): Howard Y. Chang, MD, PhD

Cancer Type: Breast, Leukemias

Research Area: Epigenetics

Dr. Schmidt [Norman B. Leventhal Fellow] focuses on the brain cancer glioblastoma multiforme, one of the most malignant, invasive and difficult-to-treat brain tumors. He aims to develop innovative research tools (bioengineered molecules) to investigate the role of critical proteins, ion channels, in glioblastoma growth and metastasis. These findings will lead to a better understanding of how ion channel disorders contribute to cancer development. Ion channels may represent new targets for cancer therapy.

Project Title: "Molecular-targeted reagents to probe the role of ion channels in glioblastoma oncogenesis, proliferation, and migration"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): Edward S. Boyden, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: Biomedical Engineering

Dr. Scott-Browne [Fraternal Order of Eagles Fellow] is studying a recently identified modification of DNA, called 5-hydroxymethylcytosine, to understand how it controls expression of different genes and influences the development of immune cells. As this DNA modification is mutated in certain leukemias, his research may lead to new understanding of these cancers.

Project Title: "Function and genomic stability of 5-hydroxymethylcytosine"

Institution: La Jolla Institute for Allergy and Immunology

Sponsor(s) / Mentor(s): Anjana Rao, PhD

Cancer Type: All cancers, Leukemias

Research Area: Epigenetics

Dr. Sims is using biochemistry and mathematical modeling to study the molecular mechanisms by which cells commit to programmed cell death. Tumor cells acquire changes that allow them to evade this fate, a property that is critical for disease progression and often underlies resistance to treatment.

Project Title: "Regulation of mitochondrial apoptosis"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Peter K. Sorger, PhD

Cancer Type: All cancers

Research Area: Cell Death

A great deal of cancer research focuses on investigating the methods by which tumors cope with damage to their DNA.  Less is known about the ways cancer cells deal with damage to any of the thousands of proteins necessary for cell survival.  Cancerous cells often occupy environments that subject them to numerous stresses, including oxygen and nutrient depletion, which can lead to protein damage or misfolding.  To survive and proliferate in these conditions, cancer cells use specific protective mechanisms to destroy or restore damaged proteins; in contrast, normal cells would die in such surroundings. 

Cancer cells may, for example, activate degradation pathways to do away with dysfunctional proteins.  Dr. Elias proposes that cancer cells may also promote long-term survival by dividing asymmetrically, thus producing one daughter cell free of damaged proteins.  To test these ideas, he will measure the lifetimes of damaged proteins, model the processes cancer cells use to dispose of proteins, and investigate the ways by which these methods contribute to tumor formation.  By understanding the mechanisms cancer cells depend on to escape death and promote growth, he hopes to discover new treatments and diagnostics, as well as ways to better target existing therapeutics to individual patients’ cancers.

Project Title: "How cancers cope with damage: a proteomics approach"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Proteomics

Despite decades of research, how cell growth and proliferation are coordinated with the metabolism in a cell has remained a critical unresolved question.  Understanding these specific mechanisms would address the long-standing question of how cells assess their metabolic and nutritional state to decide when to proliferate.

Dr. Tu has discovered a key mechanism by which carbon sources, such as glucose, signal cells to grow and divide; these studies were conducted in the model organism, baker's yeast.   His goal is to investigate these mechanisms in mammalian cells and determine whether such mechanisms can be exploited to selectively kill rapidly proliferating cancer cells.  He also aims to explore whether novel, unconventional metabolic strategies might be highly effective for the treatment of a variety of cancers.

Project Title: "A novel strategy for attacking tumors based on the identification of a fundamental carbon-source signal driving cell growth"

Institution: UT Southwestern Medical Center

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Biochemistry

Nutrient metabolism in cancer cells is different from that in most normal cells.  This metabolic difference has not yet been exploited for therapy. 

Dr. Vander Heiden aims to rigorously define how altered cell metabolism contributes to cancer cell proliferation; he seeks to elucidate exactly how nutrients are used by cancer cells.  This approach will lead to a better understanding of how specific metabolic pathways are used to help cancer cells grow, and holds the key to targeting metabolism for better cancer treatments.

Project Title: "Understanding the metabolic requirements of cancer cells"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Biochemistry

About one half of the human genome is occupied by sequences of DNA called transposable elements that can move within the genome, damaging normal genes and causing mutations or chromosomal rearrangements.  Often referred to as “junk DNA,” several lines of research highlight the importance of transposable elements in cancer development.

Dr. Aravin’s goal is to comprehensively investigate the role that transposable elements play in cancer.  He will study how transposable elements mobilize, their effect on gene regulation, and how they contribute to cancer initiation and growth.  His research will provide a better understanding of tumorigenesis and may form the basis for new diagnostic and therapeutic strategies for cancer.

Project Title: "Epigenetic regulation of transposable elements in cancer"

Institution: California Institute of Technology

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Epigenetics

The ability to undergo cell division is encoded in the genomes of all human cells. This process requires a symphony of growth genes to be turned on, and then silenced when cell division is no longer needed. The activation of the growth program in healthy cells is conducted by a small number of master regulatory genes called transcription factors. In contrast, abnormal unrestricted cell growth is encoded in the genomes of all cancer cells. This uncontrolled growth is attributable to acquired mutations in the genome, which result in hyperactivity of the master regulators. Many people in the field of cancer research regard these master regulators as the most desirable targets for drug discovery. Unfortunately, developing drugs against these proteins has proven to be technically difficult.

Dr. Bradner is using new chemical approaches to develop small molecule drugs directed at the master regulators of cancer cell growth. The primary focus of his efforts is a master regulator called Myc. Abnormal activation of Myc is one of the most common events in all human cancers. By targeting Myc in cancer cells, he hopes to discover new, prototype drugs that can be used as more effective targeted anti-cancer agents.

Project Title: "Targeting epigenetic readers as cancer therapy"

Institution: Dana-Farber Cancer Institute

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Chemical Biology

The well-established link between inflammation and cancer is exemplified by Crohn’s disease, a severe intestinal disorder that afflicts millions world-wide. The chronic inflammation and repetitive tissue injury associated with this disease increase the risk of developing small intestinal and colorectal cancer. Although several mutations in genes have been identified that are important for Crohn’s disease, it remains unclear why these mutations cause disease in some people and not others.

Dr. Cadwell generated mice with mutations in the Crohn’s disease gene ATG16L1 during his time as a Damon Runyon Fellow.  He found that ATG16L1 mutant mice develop intestinal inflammatory disease, but only after infection with a virus called MNV.  Common viral infections underlie many chronic diseases and are prominent in cancer.  In this respect, the ATG16L1 mutant mouse model provides a tremendous opportunity to investigate a viral triggering event that leads to inflammation and disease.  His goal is to examine how viral infections and genetic susceptibility combine to generate inflammation, and by doing so, better understand the early events in disease.

Project Title: "Characterization of mice deficient in autophagy protein Atg16L1"

Institution: New York University School of Medicine

Sponsor(s) / Mentor(s): n/a

Cancer Type: Colorectal, Gastric

Research Area: Infectious Disease

Dr. Lu is designing a novel technique to study cellular reactions called ubiquitination and deubiquitination, which are essential for normal biological processes and are often mutated in cancer. He will examine single molecules in cell extracts, with the goal of gaining insights into the role of these reactions in cancer development and growth.

Project Title: "Single-molecular study of ubiquitination/deubiquitination kinetics in cell extracts"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Marc W. Kirschner, PhD

Cancer Type: All cancers

Research Area: Biophysics

Dr. Moellering [HHMI Fellow] is investigating whether cancer cells use small molecule signaling, known as quorum-sensing, to communicate and thus control tumor initiation, growth and metastasis. Such mechanisms are well characterized in other complex cellular populations, such as bacteria, but none have been discovered yet in human cancer. Understanding this form of cancer cell communication will provide insights into many aspects of tumor progression and may identify new opportunities for therapeutic intervention.

Project Title: "Characterization of novel pathogenic pathways in cancer: do tumor cells use quorum-sensing molecules to support malignancy?"

Institution: The Scripps Research Institute

Sponsor(s) / Mentor(s): Benjamin F. Cravatt, PhD

Cancer Type: All cancers

Research Area: Chemical Biology

Dr. Yang [HHMI Fellow] is developing theoretical models and quantitative experiments to capture the fundamental principles that govern the robust oscillations in early embryonic cell cycles. These principles may reveal a better understanding of cancer development and new possibilities for therapeutic intervention.

Project Title: "Nonlinear coupling of positive and negative feedback loops in Xenopus early embryonic cycles"

Institution: Stanford University

Sponsor(s) / Mentor(s): James E. Ferrell, MD, PhD

Cancer Type: All cancers

Research Area: Proliferation/Cell Cycle

Dr. Thomsen [Suzanne and Bob Wright Fellow] is studying the mechanism by which a newly discovered class of small molecules can activate enzymes known as caspases and induce programmed cell death (apoptosis) in cancer cells. Disruption of apoptosis is a defining feature of many cancers. Understanding the mechanism of small molecule-induced caspase activation may thus directly contribute to the rational design of improved cancer therapies.

Project Title: "Molecular and cellular mechanism of caspase activation by small molecule proenzyme activators"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): James A. Wells, PhD

Cancer Type: All cancers

Research Area: Chemical Biology

Dr. Yun is studying metabolic pathways or enzymes that are regulated by cancer-causing genes in colorectal cancer. Her research will contribute to the development of cancer therapies that effectively target pathways involved in the unique aspects of cancer cell metabolism.

Project Title: "Discovering novel metabolic pathways and enzymes altered by oncogenes"

Institution: Beth Israel Deaconess Medical Center

Sponsor(s) / Mentor(s): Lewis C. Cantley, PhD

Cancer Type: Leukemias, Lymphomas

Research Area: Stem Cell Biology

Dr. Osborne [HHMI Fellow] is examining asymmetric cell division, a process that when disrupted has been linked to cancer occurrence and progression. By combining deep sequencing technology with single-cell dissection, she hopes to fully characterize unequal RNA transcript partitioning that occurs during asymmetric cell division and to identify cellular components important for cancer occurrence, prevention and therapy.

Project Title: "When paths diverge: patterns and mechanisms of asymmetric cell division"

Institution: University of North Carolina, Chapel Hill

Sponsor(s) / Mentor(s): Jason D. Lieb, PhD

Cancer Type: All cancers

Research Area: Genomics

Dr. Kim [HHMI Fellow] is investigating how sexually reproducing organisms faithfully transmit their genetic information from parent to progeny through a specialized cell division called meiosis. Understanding the mechanisms that ensure accurate chromosome segregation during a cell division is imperative to designing effective cancer therapeutics.

Project Title: "Identification of the signaling cascades regulating meiotic chromosome dynamics"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Abby F. Dernburg, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Yan [HHMI Fellow] is aiming to generate profiles of phosphorylation for each kinase and phosphatase enzyme in the genome, and to relate these profiles to their in vivo functions during development. Given the large number of kinase mutations associated with various cancers, understanding the phosphorylation network could prompt treatment tailored to aberrant signaling of specific pathways.

Project Title: "Building a kinase and phosphatase network using phosphorylation signatures"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Norbert Perrimon, PhD

Cancer Type: All cancers

Research Area: Signal Transduction

Dr. Heller is developing a method to direct gene therapies to cancerous tissues.  He is synthesizing polymer nanoparticles that can target tumors using specific receptors on their surface.

Project Title: "Molecularly imprinted polymeric antibodies for tumor-targeted siRNA delivery"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): Robert S. Langer, ScD

Cancer Type: All cancers

Research Area: Experimental Therapeutics

Dr. Reuter is characterizing the genomic landscape of primary human cancers using high-throughput sequencing technologies. In principle, whole genome sequencing can elucidate the entire suite of mutations responsible for cancer development in an individual. However, distinguishing cancer causing mutations from benign passenger mutations based on DNA sequence alone remains challenging. By integrating whole genome information from both the DNA and RNA, he hopes to identify novel somatic mutations in protein-coding genes, non-coding RNAs and regulatory elements in the genome. A more complete understanding of the mutations responsible for cancer development should enhance prognostic accuracy, inform treatment strategies and uncover novel therapeutic opportunities.

Project Title: "Integrative analysis of human cancers using high throughput sequencing"

Institution: Stanford University

Sponsor(s) / Mentor(s): Michael P. Snyder, PhD

Cancer Type: All cancers

Research Area: RNA

Dr. Lander [Merck Fellow] is using electron microscopy to provide a better understanding of the dynamic nature of microtubules - polymers that are crucial for cellular structure and function. These proteins are an important molecular target for cancer treatment.

Project Title: "Structural basis of GTP hydrolysis in microtubule dynamic instability"

Institution: Lawrence Berkeley National Laboratory

Sponsor(s) / Mentor(s): Eva Nogales, PhD

Cancer Type: All cancers

Research Area: Structural Biology

Dr. Evason [Robert Black Fellow] is studying liver development and liver tumor formation in zebrafish. Her focus is on hepatic stellate cells, support cells that surround both normal liver tissue and liver tumors.  She hopes to improve our understanding of how these cells influence liver cancer, including ways by which hepatic stellate cells might promote formation of liver tumors and/or lead to more aggressive tumor behavior.

Project Title: "Hepatic stellate cell development and role in carcinogenesis"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Didier Y.R. Stainier, PhD

Cancer Type: Liver

Research Area: Developmental Biology

Dr. Joshi is studying the response of the body’s immune system to tumors.  The goal of his research is to understand how cells of the immune system interact with growing tumors and why these cells are not able to effectively kill tumors.  One particular type of immune cell, the regulatory T cell, blocks anti-tumor immune cells from killing tumor cells.  Understanding how regulatory T cells function and how they promote tumor growth may be critical to developing future immune-based treatments and therapies for cancer patients. 

Project Title: "Understanding the development and function of regulatory T cells in an autochthonous mouse model of human non-small cell lung cancer"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): Tyler Jacks, PhD

Cancer Type: Lung

Research Area: Tumor Immunology

Dr. Schweikhard is investigating, at the single molecule level, how certain transcription factors assist an enzyme called RNA polymerase II in faithfully copying the genetic information stored in our DNA to messenger RNA—the blueprint for the proteins in our body. Aberrant gene expression lies at the heart of cancer, and thus, a detailed understanding of the activities of specific transcription factors may open up a potential route toward cancer therapy.

Project Title: "A single-molecule study of factors TFIIS and TFIIF during transcriptional elongation by RNA polymerase II"

Institution: Stanford University

Sponsor(s) / Mentor(s): Steven M. Block, PhD

Cancer Type: All cancers

Research Area: Biophysics

Dr. Hendrickson [Robert Black Fellow] aims to identify and describe RNA molecules called lincRNAs that may regulate how cancer cells read genetic information. Defining the roles of lincRNAs in cancer could open new avenues for more accurate diagnostics and effective therapeutics.

Project Title: "A guiding role for lincRNAs in the establishment of cancer-like epigenetic landscapes"

Institution: Harvard University

Sponsor(s) / Mentor(s): John L. Rinn, PhD

Cancer Type: All cancers

Research Area: Chromatin Biology

Dr. Skwarek [Robert Black Fellow] is examining epithelial-to-mesenchymal transitions (EMTs), cellular changes that are required for normal development.  EMTs are also crucial benchmarks in tumor progression towards metastasis.  She will be performing a genetic screen for new molecules involved in EMTs.  These studies will broaden our knowledge of the role of EMTs in cancer progression with the additional goal of identifying new targets for cancer therapeutics. 

Project Title: "In vivo identification of novel regulators of epithelial-mesenchymal transition"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): David Bilder, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Duncan [HHMI Fellow] is examining how DNA-sequence-independent (epigenetic) mechanisms regulate gene expression during regeneration in the planarian flatworm.  Such mechanisms are involved in the establishment and maintenance of cellular memory; understanding the normal function of epigenetics will lead to a better understanding of how their misregulation leads to cancer.

Project Title: "Epigenetic regulation of cellular memory during planarian regeneration"

Institution: Stowers Institute for Medical Research

Sponsor(s) / Mentor(s): Alejandro Sánchez Alvarado, PhD

Cancer Type: All cancers

Research Area: Developmental Biology

Dr. Lyssiotis [Amgen Fellow] is studying how oncogenes affect cellular metabolism in cancer. In particular, he is interested in understanding (i) how mutations in the oncogene Kras alter cellular metabolism in pancreatic ductal adenocarcinoma to facilitate cell growth and (ii) if distinct components of KRas-mediated metabolic reprogramming can be targeted for therapeutic gain. Ultimately, this work aims to translate our understanding of pancreatic cancer cell metabolism into therapies for this devastating disease.

Project Title: "Exploring the metabolic effects of oncogenic KRas in pancreatic ductal adenocarcinoma"

Institution: Beth Israel Deaconess Medical Center

Sponsor(s) / Mentor(s): Lewis C. Cantley, PhD

Cancer Type: Pancreatic

Research Area: Biochemistry

 Dr. Krukenberg [Fayez Sarofim Fellow] is studying the cellular regulation and function of the molecule poly(ADP-ribose). Poly(ADP-ribose) is a poorly understood molecule that is involved in many essential biological processes including cell division and cell death. By understanding the role of this molecule in both cancer and non-cancer cells, she will investigate new avenues for the design of more effective and selective cancer therapeutics.

Project Title: "Understanding the cell biological function of poly(ADP-ribose) and its role in cancer "

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Timothy J. Mitchison, PhD

Cancer Type: All cancers, Breast

Research Area: Cell Biology

Dr. Hua aims to complete a comprehensive, genome-wide assessment of regulatory networks governing self-renewal and fate-determination programs in normal and malignant neural stem cells.  Tumor progression of certain tumor types, including glioblastoma, depends on a subpopulation of cells within the tumor called tumor stem cells.  Understanding the shared and distinct features of normal and malignant stem cells is critical to develop novel therapies that selectively target tumor stem cells but spare their normal counterparts.

Project Title: "Genomic analysis of core transcriptional regulatory networks in normal and malignant neural stem cells"

Institution: MD Anderson Cancer Center

Sponsor(s) / Mentor(s): Ronald A. DePinho, MD

Cancer Type: Brain, Neuro-oncology

Research Area: Genomics

Dr. Lydeard is interested in studying how proteins are targeted for destruction. Defects in maintaining the balance between newly made proteins and those to be destroyed are often linked with cancer progression. Better understanding of how these processes are regulated will help to develop more effective anticancer therapeutics.

Project Title: "Defining CRL4 substrates and regulators through a systematic proteomic and functional analysis of DCAFs"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Jeffrey Wade Harper, PhD

Cancer Type: All cancers

Research Area: Proteomics

Dr. Bradshaw is studying the regulation of an enzyme called protein phosphatase that acts in specific cells to promote cellular differentiation.  Protein phosphatases are required for many processes, including cell growth, division, differentiation and stress adaptation.  He hopes that understanding phosphatase regulation will clarify the role of these enzymes in cancer and potentially aid in the development of anti-cancer therapies that target phosphatases.

Project Title: "Regulation of the SpoIIE phosphatase and activation of a cell-specific transcription factor"

Institution: Harvard University

Sponsor(s) / Mentor(s): Richard M. Losick, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Wong [Merck Fellow] is developing a new experimental platform for characterizing how cancer cells migrate in response to biochemical signals and 3D structural architectures. This approach may yield novel insights into how malignant cancer cells invade, which would aid the development of anti-metastatic therapies.

Project Title: "Suppressing cancer cell invasion and plasticity in 3D microenvironments"

Institution: Massachusetts General Hospital

Sponsor(s) / Mentor(s): Mehmet Toner, PhD, and Daniel Irimia, MD, PhD

Cancer Type: All cancers

Research Area: Biomedical Engineering

Dr. Muzzey [HHMI Fellow] is studying how both the sequence and structure of mRNAs affect the efficiency by which they are translated into protein in the yeast Candida albicans. Defects in mRNA translation have been linked to several cancers, and he hopes to reveal features of translational control that generalize to humans. Additionally, his project may highlight potential ways to combat Candida infections, which frequently afflict immune-compromised cancer patients undergoing therapy.

Project Title: "Resolving general principles of cis translational regulation in eukaryotes using high-throughput and mechanistic analyses of allelic expression in Candida albicans"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Jonathan S. Weissman, PhD

Cancer Type: All cancers

Research Area: Genomics

Dr. Hale [HHMI Fellow] is focusing on the basic biological processes that allow cells to coordinate the replication of their genes with the regulation of when those genes are turned on/off.  By studying the interplay of these two biological processes, he hopes to elucidate how tumor cells are able to bypass the strict controls that a cell uses to normally operate each process.

Project Title: "Understanding how a histone methyltransferase links DNA replication, repair and transcription"

Institution: University of California, Los Angeles

Sponsor(s) / Mentor(s): Steven E. Jacobsen, PhD

Cancer Type: All cancers

Research Area: Genomics

Basal cell carcinoma (BCC) is the most common type of skin cancer.  Mutations in the Hedgehog (HH) signaling pathway are frequently found in these cancers.  Early-stage clinical studies of a HH pathway inhibitor drug have been successful, with 55% of patients reported to respond.  However, most tumors change during the course of therapy and drug resistance eventually develops. 

Dr. Tang, a dermatologist, will characterize mechanisms of drug resistance and identify new drug combinations that are effective in treatment of BCC.  The ultimate goal of her research is to prevent or delay drug resistance.  Her studies have the potential to benefit patients with BCC as well as those with other HH-dependent cancers, such as medulloblastoma.

Project Title: "Mechanisms of acquired resistance to Hedgehog pathway inhibitors in basal cell carcinomas"

Institution: Stanford University

Sponsor(s) / Mentor(s): Philip A. Beachy, PhD, and Ervin H. Epstein, MD

Cancer Type: Skin

Research Area: Immunotherapy

Certain types of lymphoma, such as the indolent B cell lymphomas and mantle cell lymphoma, are incurable with standard therapies.  These diseases can, however, be cured using stem cell transplantation, in which immune T cells from the donor kill lymphoma cells.  This procedure unfortunately carries the serious risk of graft-versus-host disease, which can be life-threatening.

In order to provide safer therapy options, Dr. Till [Damon Runyon-Pfizer Clinical Investigator] aims to develop a new treatment for lymphoma using patients’ own T cells to fight their cancers: patient cells are collected, a gene is inserted into the cells that allows them to recognize and kill lymphoma cells, and then the cells are infused back into the patient.  He is leading a phase I clinical trial testing this treatment in lymphoma patients.  He is optimistic that this strategy will translate into a safe, curative treatment for patients with lymphoma; insights from this work may help to advance similar treatments for other types of cancer.

Project Title: "Optimization of adoptive immunotherapy for lymphoma using genetically modified CD20-specific T cells"

Institution: Fred Hutchinson Cancer Research Center

Sponsor(s) / Mentor(s): Oliver W. Press, MD, PhD

Cancer Type: Lymphomas

Research Area: Immunotherapy

Bone marrow transplantation, or allogeneic hematopoietic stem cell transplant (HCT), is the only curative therapy for many patients with leukemia.  Certain immune cells, called T cells, contained in the donor HCT graft can cause a “graft versus leukemia” (GVL) effect which eliminates leukemic cells.  Unfortunately, there are also donor T cells in the HCT graft that can cause a condition called “graft versus host disease” (GVHD).  GVHD is a life-threatening immune response that remains the major barrier to the success of transplantation. 

Dr. Bleakley [Richard Lumsden Foundation Investigator] focuses on developing new approaches to separate the beneficial GVL effect from detrimental GVHD after bone marrow transplantation.  Her goal is to identify specific subsets of immune cells that promote GVHD; these cells can then be eliminated to reduce the frequency or severity of GVHD, while at the same time maintaining and improving the GVL effect.  In addition, she aims to discover novel leukemia-associated proteins that could be potential targets for therapeutics.

Project Title: "Segregating the GVL effect from GVHD in humans"

Institution: Fred Hutchinson Cancer Research Center

Sponsor(s) / Mentor(s): Stanley R. Riddell, MD

Cancer Type: Leukemias

Research Area: Immunotherapy

Dr. Carling [Doris Duke-Damon Runyon Clinical Investigator] focuses on endocrine tumors, a type of cancer that affects hormone-producing tissues in the body (such as the thyroid, pituitary gland, adrenal gland and islet cells of the pancreas).  The underlying genetic basis for endocrine tumors is not yet known.  Dr. Carling’s goal is to complete a comprehensive genomic analysis of patients with endocrine tumor disease in order to identify individual genes involved in early cancer formation.  His research will provide important insights into the development of endocrine tumors as well as other cancer types, laying the basis for future individualized medical and surgical management of cancer. 

Project Title: "Molecular genetics of endocrine tumor disease"

Institution: Yale University School of Medicine

Sponsor(s) / Mentor(s): Richard P. Lifton, MD, PhD, and Robert Udelsman, MD

Cancer Type: Neuroendocrine, Thyroid

Research Area: Cancer Genetics

Heritable factors are an important determinant of cancer risk.  At present, a large portion of the genetic basis of cancer predisposition remains unexplained. 

Dr. Stadler is a clinical geneticist whose research goal is to determine the genetic basis of “sporadic” cancers in young adults.  She will be testing the hypothesis that de novo (spontaneous) chromosomal changes in the genome are associated with testicular germline cancer.  High-resolution sequencing technology will be used to compare the whole genomes of patients to those of their parents, with the goal of identifying rare genetic variants associated with cancer susceptibility.  This approach represents a new paradigm in cancer genetics, which could have broad applications in terms of cancer risk stratification and cancer prevention.

Project Title: "Characterization of de novo germline genetic alterations in cancer susceptibility"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Kenneth Offit, MD, MPH, and Michael H. Wigler, PhD

Cancer Type: Breast, Colorectal, Testicular

Research Area: Cancer Genetics

Novel therapeutic approaches are necessary to improve the outcome of patients with sarcomas and other solid tumors.  Dr. Matushansky [Damon Runyon-Gordon Family Clinical Investigator] aims to test his hypothesis that chromatin remodeling agents, which alter gene expression, can induce solid tumors to undergo biological and morphological changes that lead them to resemble their corresponding normal tissue, a process referred to as maturation or differentiation.  Maturation or differentiation therapy provides an opportunity to fundamentally change the biology of the underlying cancer (and thus its overall prognosis).  While a change of an undifferentiated/high-grade sarcoma (or carcinoma) into completely normal tissue remains an ideal, albeit likely unrealistic goal, a change from a ‘poorly differentiated/high-grade’ tumor to a ‘well-differentiated/low-grade’ tumor is attainable; this can improve an individual’s median time of survival from months to decades.  Dr. Matushansky hopes to implement this therapeutic approach for sarcomas and other solid tumors.

Project Title: "Implementing and imaging epigenetic based differentiation therapy for solid tumors"

Institution: Columbia University

Sponsor(s) / Mentor(s): Carlos Cordon-Cardo, MD, PhD

Cancer Type: Sarcomas

Research Area: Experimental Therapeutics

Tumors depend on new blood vessel formation for growth and spread.  This process, known as angiogenesis, is an attractive target for cancer therapy.  Unfortunately, antiangiogenic agents have proven less efficacious than anticipated.  Preclinical results suggest that combinations of antiangiogenic agents and radiation may have great therapeutic utility; however, it remains unclear how these treatment modalities interact and how best to integrate them.

Dr. Kozak [Damon Runyon-Genentech Clinical Investigator] will use biochemical, cellular and animal models to develop strategies to optimally integrate antiangiogenic therapies with radiation.  Positron emission tomography (PET) will be used for non-invasive monitoring of angiogenesis in mouse tumor models, and these results will be correlated to treatment responses.  Guided by results of these studies, he plans to initiate a pilot human trial of antiangiogenic therapy to determine if PET imaging can identify a therapeutic window during which radiation may be particularly effective.  The proposed project represents an integrated “bench-to-bedside” effort to optimize antiangiogenic therapy.

Project Title: "Radiosensitization with antiangiogenic therapy"

Institution: University of Wisconsin

Sponsor(s) / Mentor(s): Paul M. Harari, MD

Cancer Type: All cancers

Research Area: Experimental Therapeutics

Ewing’s sarcoma is the second most common bone tumor in children and adolescents.  Patients have a poor prognosis, yet the causes of the disease are not understood.  Certain genetic changes have been linked to Ewing’s sarcoma: a specific translocation (joining of two different chromosome parts) and microsatellites (series of repeating DNA sequences).  Another reported observation is increased development of hernias in patients with this disease. 

Dr. Schiffman, a pediatric oncologist, is interested in understanding the underlying molecular genetics of Ewing’s sarcoma.  He will take a genetic epidemiologic approach to studying the disease, by examining the genes of parent-child trios: patients with Ewing’s sarcoma and their parents.  He will examine inheritance of DNA microsatellites and genetic changes associated with hernia development.  This study will identify novel genetic risk factors for Ewing’s sarcoma, which can be used for future preventative and therapeutic strategies.

Project Title: "Microsatellite length and integrin signaling as risk factors for Ewing's Sarcoma"

Institution: University of Utah

Sponsor(s) / Mentor(s): Stephen L. Lessnick, MD, PhD

Cancer Type: Ewing’s Tumors

Research Area: Cancer Genetics

Due to advances in cancer screening and treatments, the majority of women diagnosed with breast cancer will be cured of their disease.  However, many will require at least five years of therapy with medications called aromatase inhibitors, which greatly reduce the amount of estrogen circulating in the body.  These drugs cause new or worsening aches and pains in about half of women taking them, resulting in decreased quality of life. 

One hypothesis is that medication-induced lowering of estrogen levels may affect pain perception, resulting in increased sensation of pain during therapy.  In order to evaluate this hypothesis, Dr. Henry [Damon Runyon-Lilly Clinical Investigator] will conduct a clinical trial to assess change in pain threshold and development of aches and pains in women who are being treated with an aromatase inhibitor.  In addition, she will determine if there is a link between pain symptoms during treatment and inherited mutations in genes involved in pain perception; this will address whether some women are predisposed to developing symptoms during aromatase inhibitor therapy. The overall goal is to gain a better understanding of why pain symptoms occur, so that these symptoms can be prevented or treated, thereby improving the quality of life of breast cancer survivors.

Project Title: "Pain processing pathway analysis in aromatase inhibitor-associated musculoskeletal syndrome"

Institution: University of Michigan

Sponsor(s) / Mentor(s): Daniel F. Hayes, MD

Cancer Type: Breast

Research Area: Pharmacogenomics and Biomarkers

Cancer cells use specific metabolic pathways to fuel their growth into tumors.  A great deal of work has already defined some of these pathways that allow cancer cells to grow in the laboratory, but very little is known about which pathways drive the growth of actual tumors in cancer patients. 

Dr. DeBerardinis aims to understand the role of metabolism in tumor growth and to use these findings to improve treatment of cancer.  He plans to use novel, highly sensitive methods to study metabolic activity in vivo in primary human glioma brain tumors, and to image these activities in growing tumors.  This approach should also be applicable to other cancer types and will be important for disease imaging and therapy.

Project Title: "Translational studies in cancer metabolism"

Institution: UT Southwestern Medical Center

Sponsor(s) / Mentor(s): Helen H. Hobbs, MD

Cancer Type: All cancers

Research Area: Cell Biology

Dr. Hartl [Robert Black Fellow] is studying the Hedgehog (Hh) signaling pathway, which is required for the proper growth, patterning and function of specialized cellular tissues. When the Hh pathway goes awry, increased cell growth signals can lead to tumorigenesis. Previous work has demonstrated that a specific lipid molecule can induce the Hh pathway to go awry. His research focuses on how this lipid alters the Hh pathway; he hopes that his findings will lead to better methods of cancer treatment.

Project Title: "The role of lipids in Hedgehog signal transduction"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): Matthew P. Scott, PhD

Cancer Type: All cancers

Research Area: Neuroscience

Dr. Guydosh [HHMI Fellow] is studying how proteins are manufactured in cells. Small changes in this process can lead to the production of defective proteins and result in many types of cancer.

Project Title: "Genome-wide regulation and dynamics of ribosome elongation"

Institution: The Johns Hopkins University

Sponsor(s) / Mentor(s): Rachel D. Green, PhD

Cancer Type: All cancers

Research Area: RNA

Dr. Mathew [HHMI Fellow] is studying how cell identity is maintained throughout the life of an organism. She is focusing on the role of chromosome modifications in this process. Failure to maintain cell identity has catastrophic consequences, often resulting in cancer or other diseases.

Project Title: "Revealing epigenetic changes that underlie cellular memory"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Danesh Moazed, PhD

Cancer Type: All cancers

Research Area: Epigenetics

Dr. Spencer is studying the cellular decision to proliferate or remain in a non-dividing state. Using fluorescence time-lapse microscopy and mathematical modeling, she is working to extend our current understanding of this cellular decision and its deregulation in cancer.

Project Title: "Protein expression dynamics and thresholds in cell cycle commitment"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): Tobias Meyer, PhD

Cancer Type: All cancers

Research Area: Proliferation/Cell Cycle

Dr. Dawlaty is studying DNA methylation, a type of modification that regulates gene expression during various biological processes including cancer and development. Recently, it has been shown that the Tet family of enzymes (Tet1/2/3) can convert 5mC to 5-hydroxymethylcytosine (5hmC). 5hmC is abundant in embryonic stem cells and adult tissues. His goal is to generate and utilize genetically modified mice lacking the Tet proteins in order to establish the biological relevance and in vivo requirements of Tet proteins and 5hmC in cancer and development.

Project Title: "Role of 5hmC and Tet proteins in cancer and development"

Institution: Whitehead Institute for Biomedical Research

Sponsor(s) / Mentor(s): Rudolf Jaenisch, MD

Cancer Type: Brain, Neuro-oncology

Research Area: Epigenetics

Dr. Kafsack [HHMI Fellow] is examining how cell behavior is dependent on cell density (the number of other cells nearby). He is using the parasite Plasmodium falciparum as an experimental model. His goal is to apply this knowledge to understanding how cancer cells respond to their surrounding environment, resulting in tumor growth and metastasis.

Project Title: "Density-dependent autocrine control of gametocytogenesis in the virulent malaria parasite Plasmodium falciparum"

Institution: Princeton University

Sponsor(s) / Mentor(s): Manuel Llinás, PhD

Cancer Type: All cancers

Research Area: Genomics

Dr. Stanley aims to understand how autophagy, the process of cellular "self-digestion," is regulated in the cell. She hopes that her research will help shed light on the role of autophagy in different types of cancer.

Project Title: "Structural and biochemical characterization of the autophagy specific class 3 phosphatidylinositol 3-phosphate complex"

Institution: National Institute of Diabetes and Digestive and Kidney Diseases

Sponsor(s) / Mentor(s): James H. Hurley, PhD

Cancer Type: All cancers

Research Area: Structural Biology

Dr. Smith [HHMI Fellow] is investigating how the higher-order structure of DNA is accurately transmitted when cells divide. Defects in this process are likely to play a role in the early stages of oncogenesis by giving rise to inappropriate gene expression.

Project Title: "Lagging strand synthesis and chromatin replication"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Iestyn Whitehouse, PhD

Cancer Type: All cancers

Research Area: Epigenetics

Dr. Gabel is investigating how dysfunction of ubiquitin ligase UBE3A, an enzyme that normally regulates amounts of specific proteins in the cell, leads to diseases such as the neurodevelopmental disorder Angelman Syndrome and common cervical cancers. These studies can provide important insights into the mechanism of disease.

Project Title: "Dissecting the mechanism and function of Arc regulation by the Angelman Syndrome-associated ubiquitin ligase Ube3a"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Michael E. Greenberg, PhD

Cancer Type: Gynecological

Research Area: Neuroscience

Dr. Zidovska is using novel physical approaches to measure the dynamics of chromatin (DNA and its associated proteins) in the cell nucleus. Her findings may lead to a new understanding of the role and origin of chromatin dynamics and their critical function in cancer.

Project Title: "Collective chromatin dynamics: exploring chromatin positional fluctuations in interphase"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Timothy J. Mitchison, PhD

Cancer Type: All cancers

Research Area: Biophysics

[Island Outreach Foundation Innovator of the Damon Runyon-Rachleff Innovation Award]
Defining new paradigms to understand drug resistance

New targeted therapies have been successful in treating certain cancers.  For example, for lung cancer, Iressa and Tarceva produce encouraging responses in Non-Small Cell Lung Carcinomas (NSCLC) with specific gene mutations.  However, clinical data shows that the tumors inevitably develop drug resistance, which results in relapse within a few years.  Currently it is not well understood how cancers develop resistance to drugs over time. 

Dr. Sordella aims to characterize drug-resistant lung cancer cells at the molecular and genetic levels, defining the requirements for their survival and ability to spread.  The ultimate goal of this research is to develop methods to therapeutically target these tumor cells in lung cancer as well as in other cancer types.   

Dr. Sordella said, “While risky, this project has the potential to provide life-changing benefits for a large number of cancer patients.  I am very grateful to the Damon Runyon and Island Outreach Foundations for this grant, which will allow us to fast-track this research.  Given the prestige associated with this Damon Runyon Award, I also hope that it will help us to gain additional funding from other sources."

Project Title: "Characterization of Erlotinib resistant, Mesenchymal and Metastatic (EMM) cells present in naïve lung tumors prior to treatments"

Institution: Cold Spring Harbor Laboratory

Sponsor(s) / Mentor(s): n/a

Cancer Type: Lung

Research Area: Invasion and Metastasis

Unraveling an old mystery using new technology

Scientists have known since the 1920s that one distinguishing characteristic of cancer cells is their altered glucose metabolism: compared to normal cells, cancer cells have a “sweet tooth” and use much more glucose from the environment.  This discovery has yet to be exploited for therapeutic benefit.

Dr. Christofk’s goal is to investigate mechanisms by which oncogenes and tumor suppressor genes establish this altered metabolism in cancer cells.  She aims to study conserved modification sites on metabolic proteins and their role in pathway flux regulation and tumor growth.  Her research may identify novel strategies for cancer drug design.

Project Title: "Regulation of cancer metabolism"

Institution: University of California, Los Angeles

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Cancer Genetics

Applying a "systems approach" to understand cancer cell metabolism

A virologist and biochemist by training, Dr. Munger is studying the metabolic activities that are altered in cancer cells.  Whereas previous studies often focused on individual metabolic activities, Dr. Munger is taking an expanded “global" approach by examining the rates of many metabolic processes simultaneously. 
 
The goal of his research is to identify novel, cancer-specific metabolic activities and define how they are genetically triggered.  Ultimately, he plans to explore new avenues to block these activities, thereby destroying cancerous cells.

Dr. Munger said, “Most funding agencies will not fund researchers whose proposals they deem ’too ambitious,’ instead preferring 'safer' projects.  The Damon Runyon Foundation is unique in supporting the ambitious ideas of young researchers, and in this respect, they fund research that otherwise would likely not occur.  I am extremely grateful for the Foundation’s support of my laboratory’s research."

Project Title: "Elucidating mechanisms of oncogenic metabolic manipulation"

Institution: University of Rochester

Sponsor(s) / Mentor(s): n/a

Cancer Type: All cancers

Research Area: Biochemistry

Dr. Bendall is using breakthrough single-cell analysis techniques to investigate how normal regulatory cell signaling networks are rewired, allowing cancer to grow unchecked.  By understanding these events, he aims to contribute to the development of more effective diagnostics and treatments to improve clinical outcomes.

Project Title: "Improved single-cell phospho-protein signaling analysis of oncogenic progression in leukemia"

Institution: Stanford University

Sponsor(s) / Mentor(s): Garry P. Nolan, PhD

Cancer Type: All cancers, Leukemias

Research Area: Proteomics

Dr. Nguyen's [August M. Watanabe, MD, Investigator] goal is to develop novel ways of controlling donor T immune cell activity to prevent acute graft-versus-host disease (GvHD) in cancer patients treated with bone marrow transplantation. His hypothesis is that regulatory T cells (Treg) can be used to suppress GvHD while preserving beneficial anti-tumor immunity.  This work could have significant translational implications by reducing GvHD-associated mortality, thus improving the success of bone marrow transplantation in treatment of hematologic cancers such as leukemia and lymphoma.

Project Title: "Organ-specific regulatory T cells as a targeted therapy for graft-versus-host disease"

Institution: The University of Chicago

Sponsor(s) / Mentor(s): Thomas F. Gajewski, MD, PhD

Cancer Type: Leukemias, Lymphomas

Research Area: Tumor Immunology

Bladder cancer is a prevalent and deadly disease, the fourth most common cancer in men. Dr. Kim [Damon Runyon-Merck Clinical Investigator] is conducting a clinical trial examining the efficacy of erlotinib/Tarceva, an EGFR (epidermal growth factor receptor) inhibitor drug, in bladder cancer. His goal is to define predictors of patient response to erlotinib and other EGFR inhibitors and determine how to best coordinate EGFR inhibition with chemotherapy. These studies should have direct clinical impact on this deadly disease, allowing the treatment of patients most likely to benefit while minimizing unnecessary toxicity in those unlikely to respond.

Project Title: "Molecular determinants of clinical response to EGFR inhibition in bladder cancer"

Institution: University of North Carolina

Sponsor(s) / Mentor(s): Charles M. Perou, PhD & Norman E. Sharpless, MD

Cancer Type: Bladder

Research Area: Cancer Genetics

Dr. Aye [Robert Black Fellow] is studying the mechanism and regulation of ribonucleotide reductases (RNRs), enzymes that play an essential role in making deoxynucleotides (the “building blocks” of DNA).  RNRs are overexpressed in cancer cells, making them an ideal target for cancer drugs.  Her work will focus on understanding the mechanism of a new drug called Triapine, which may prevent the replication of tumor cells and is currently being tested in Phase II and III clinical trials.

Project Title: "Investigations toward mechanistic understanding of human ribonucleotide reductase ß-subunit-specific inhibition by triapine"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): JoAnne Stubbe, PhD

Cancer Type: All cancers

Research Area: Chemical Biology

Dr. Chen [HHMI Fellow] is investigating cellular and molecular mechanisms that control neural development. The goals of his research are to delineate the genetic pathways underlying formation of the neural tube and cerebral cortex, and provide a rational basis for pharmacologic and genetic therapies for patients with neurological disorders or brain tumors.

Project Title: "Genetic control of neural development and diseases"

Institution: University of Colorado Denver

Sponsor(s) / Mentor(s): Lee A. Niswander, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: Developmental Biology