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David W. Woessner, PhD

David W. Woessner, PhD

Dr. Woessner seeks to identify genetic changes that cause the most common type of childhood cancer, acute lymphoblastic leukemia (ALL). There are multiple subtypes of ALL, each with distinct genetic changes that drive disease development and influence success or failure of treatment. He has sequenced the genomes of over 1000 tumor cells from children with ALL and identified several hundred repeatedly mutated genes, for which the functions are currently unknown. He will use high throughput approaches to test the role of these changes in ALL. A better understanding of which genetic changes significantly impact cancer behavior in ALL will provide new targets for existing therapy and/or avenues for development of new drug treatments for children with ALL.

 




Project Title: "Discovery of new driver alterations in childhood ALL"

Institution: St. Jude Children's Research Hospital

Sponsor(s) / Mentor(s): Charles G. Mullighan, MBBS, MD

Cancer Type: Leukemias

Research Area: Cancer Genetics

Fuguo Jiang, PhD

Fuguo Jiang, PhD

Dr. Jiang [Merck Fellow] is studying the CRISPR-Cas system, which has been adopted as a robust and versatile platform for genome engineering in human cells as well as other experimental systems. He aims to use a combination of biochemical experiments, mutagenesis, and biophysical approaches to investigate the detailed molecular mechanism of RNA-guided DNA targeting and recognition by CRISPR-Cas9. The results of this research will provide a fundamental understanding of the Cas9 enzyme family and will support its use for site-specific genetic control, including gene therapies against cancers.




Project Title: "Molecular mechanisms of guide RNA: target dsDNA binding and PAM recognition by CRISPR-Cas9"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Jennifer A. Doudna, PhD

Cancer Type: All cancers

Research Area: RNA

Stephen Oh, MD, PhD

Stephen Oh, MD, PhD

Myeloproliferative neoplasms (MPNs) are a group of blood cancers in which a malignant cell population proliferates out of control. Myelofibrosis (MF) is one type of MPN in which the bone marrow becomes replaced by scar tissue, leading to progressive failure of normal blood cell functions and ultimately death, on average five years after initial diagnosis. MPNs, including MF, can evolve to secondary acute myeloid leukemia(sAML), which is almost invariably fatal. There is no reliable curative treatment currently available for MPNs or MF. Targeted inhibitors of a protein called JAK2 provide significant symptomatic benefit for MF patients. However, these treatments do not cure the disease, nor has it been shown that they can prevent or delay progression to sAML. Dr. Oh [Doris Duke-Damon Runyon Clinical Investigator] aims to investigate the cellular abnormalities that underlie these blood cancers. These studies have the potential to lead to the development of improved treatments for MPNs.




Project Title: "Targeting aberrant signaling pathways in myeloproliferative neoplasms"

Institution: Washington University

Sponsor(s) / Mentor(s): Daniel Link, MD

Cancer Type: Leukemias

Research Area: Signal Transduction

Luc G. Morris, MD

Luc G. Morris, MD

Head and neck cancer is a lethal malignancy that can arise in the mouth, throat, voice box, and related areas. These tumors are squamous cell cancers that are, in many cases, caused by tobacco use or human papillomavirus (HPV) infection. Head and neck cancers have many molecular similarities with squamous cell cancers of the lung and esophagus. Dr. Morris is studying several poorly-understood genes that have been recently observed to be frequently altered in head and neck cancer (as well as lung and esophageal cancer). He has found that several of these genes act as tumor suppressor genes and in their normal state, prevent tumor development. In this project, he will determine the effects of these various gene alterations on tumor growth, cancer cell survival, and the clinical prognosis of patients. This work will help to develop new ways of therapeutically targeting the pathways that promote the development of head and neck and other tobacco and HPV-associated squamous cell cancers.




Project Title: "Functionalizing tumor suppressor gene mutations and deletions in head and neck cancer"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Timothy Chan, MD, PhD and James A. Fagin, MD

Cancer Type: Head and Neck

Research Area: Genomics

Peter Hammerman, MD, PhD

Peter Hammerman, MD, PhD

The ability to define the genetic alterations that allow tumors to grow in an uncontrolled fashion has transformed our approach to cancer treatment, enabling the development of targeted therapies. Despite the initial success of targeted therapies, these treatments have limited efficacy in most diseases. Recent studies have shown that the immune cells that infiltrate a tumor play an active role in dictating the response to therapy; specific new therapies can augment the ability of the immune system to fight a cancer in combination with conventional therapies. Dr. Hammerman is using lung cancer as a model to explore genome-scale approaches to dissect this complex relationship between the tumor and its immune microenvironment. The goal of this research is to better define the optimal types of therapy for lung cancer by combining drugs that target the genetic alterations found in the tumor with those aimed at enhancing the immune response to the cancer, and to translate these observations into clinical practice.




Project Title: "Development of personalized cancer immunotherapy"

Institution: Dana-Farber Cancer Institute

Sponsor(s) / Mentor(s): Glenn Dranoff, MD, Stephen F. Hodi, MD and Kwok-Kin Wong, MD, PhD

Cancer Type: Head and Neck, Lung

Research Area: Cancer Genetics

Alejandro Gutierrez, MD

Alejandro Gutierrez, MD

It remains unclear why some patients’ tumors can be cured with chemotherapy, whereas other tumors that appear to be nearly identical are completely chemoresistant. Dr. Gutierrez focuses on this issue in a particularly high-risk subset of T-cell acute lymphoblastic leukemia, a disease that most commonly affects older children and young adults. His goals are to define the molecular basis of resistance to conventional chemotherapy in patients with this disease, and to leverage this knowledge to develop a therapeutic strategy to restore chemosensitivity. Ultimately, this could lead to significant improvements in clinical outcome for these patients.




Project Title: "Mechanisms and therapeutic targeting of EZH2-dependent chemoresistance in T-ALL"

Institution: Boston Children's Hospital

Sponsor(s) / Mentor(s): Stuart H. Orkin, MD and Anthony Letai, MD, PhD

Cancer Type: Leukemias

Research Area: Chemoresistance

Lihua Elizabeth Budde, MD, PhD

Lihua Elizabeth Budde, MD, PhD

Hematopoietic stem cell transplant is the preferred and only curative treatment for most patients with acute myeloid leukemia (AML); however, a significant percentage of patients will eventually relapse. A novel effective therapy option is therefore urgently needed. Dr. Budde [The Jake Wetchler Foundation for Innovative Pediatric Cancer Research Clinical Investigator] is testing a new strategy that uses patients’ own immune T cells, which have been modified to specifically target and kill leukemia cells. She will direct a Phase 1 clinical trial using these modified immune T cells as therapeutics for patients with AML. This trial is a first-in-human study building on her extensive preclinical research on these cells. She is also developing ways to enhance the potency of these modified immune cells in killing leukemia cells. This therapeutic approach has the potential to change the treatment paradigm and may significantly improve the cure rate for patients with leukemia.




Project Title: "Targeting CD123 using chimeric antigen receptor T cells for treatment of acute myeloid leukemia"

Institution: City of Hope

Sponsor(s) / Mentor(s): Stephen J. Forman, MD, FACP

Cancer Type: Leukemias

Research Area: Immunotherapy

Joshua Brody, MD

Joshua Brody, MD

Dr. Brody aims to develop a novel treatment approach for patients with advanced-stage lymphoma, by which the patient’s immune system is trained to recognize and eliminate his/her own cancer. This approach, an “in situ vaccine,” recruits and activates specific immune cells, dendritic cells (DC), at the location of the treated tumor—where they can then educate the rest of the immune system to recognize and eliminate tumors throughout the body. The first patients enrolled on this clinical trial have already shown the recruitment and activation of DC within the treated tumor as well as regressions of lymphoma at sites distant from the treated site. The in situ vaccine will initially be tested in patients with low-grade lymphoma, with the goal of quickly expanding to other tumor types including melanoma and head and neck cancer.




Project Title: "Flt3L-primed 'in situ' vaccination for low-grade lymphoma - Phase I/II study of intratumoral injection of rhuFlt3L and poly-ICLC with low-dose radiotherapy [NCT01976585]"

Institution: Icahn School of Medicine at Mt. Sinai

Sponsor(s) / Mentor(s): Nina Bhardwaj, MD, PhD and Miriam Merad, MD, PhD

Cancer Type: Lymphomas

Research Area: Immunotherapy

Arash Ash Alizadeh, MD, PhD

Arash Ash Alizadeh, MD, PhD

Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive lymphoma in adults.  Unfortunately, current therapies typically fail in nearly half of these patients. Dr. Alizadeh proposes a novel treatment strategy for this disease: to characterize and isolate premalignant stem cells before they transform into cancer cells. He has found that expression of a single oncogene called BCL6 is capable of reprogramming these cells from normal cells to aggressive malignant cells. He aims to define the specific genetic alterations that can give rise to this cell reprogramming. This research will be important both for understanding cancer biology, as well as for developing more effective means for treatment of lymphoma patients.




Project Title: "Targeting the malignant reprograming of early hematopoietic progenitors to mature aggressive human B-cell lymphomas"

Institution: Stanford University

Sponsor(s) / Mentor(s): Ronald Levy, MD

Cancer Type: Lymphomas

Research Area: Cancer Genetics

Mark W. Zimmerman, PhD

Mark W. Zimmerman, PhD

Dr. Zimmerman studies neuroblastoma, a tumor of the peripheral sympathetic nervous system. In high-risk neuroblastoma tumors, which account for 15% of all childhood cancer deaths, the chromatin remodeling gene CHD5 is often deleted and its loss is associated with poor prognosis. The gene expression program regulated by CHD5 has strong tumor suppressive effects and has thus emerged as a very attractive target for potential anti-cancer therapeutics. CHD5 expression is also altered in other cancer types, indicating a potential role in many different adult and pediatric malignancies. His research elucidating the CHD5 pathway in a zebrafish model of neuroblastoma will lead to significant advances in our understanding of how CHD5 functions as a tumor suppressor.




Project Title: "Elucidating the mechanism of CHD5-mediated tumor suppression in neuroblastoma"

Institution: Dana-Farber Cancer Institute

Sponsor(s) / Mentor(s): A. Thomas Look, MD

Cancer Type: Brain, Neuro-oncology

Research Area: Chromatin Biology

Ly P. Vu, PhD

Ly P. Vu, PhD

Dr. Vu is studying childhood acute myeloid leukemia (AML), a complex and heterogeneous disease. Despite exciting advances in our understanding of AML and the availability of more aggressive treatment regimens, ~30% of children still eventually relapse from this disease and there are yet no approved targeted therapies for children with AML. Her project aims to uncover the role of Syncrip, a novel RNA binding protein, in maintaining the leukemia stem cell in AML. The study will provide insights into the mechanism underlying the cause and development of AML and may lead to innovative therapeutic strategies and improved clinical outcomes for this deadly childhood disease.




Project Title: "Uncovering the role of RNA-binding protein Syncrip in acute myeloid leukemia (AML)"

Institution: Memorial Sloan Kettering Cancer Center

Sponsor(s) / Mentor(s): Michael Kharas, PhD, and Ross L. Levine, MD

Cancer Type: Leukemias

Research Area: Stem Cell Biology

Sungwook Woo, PhD

Sungwook Woo, PhD

Dr. Woo [HHMI Fellow] is using protein structures to illustrate the mechanisms of cancer-related processes. His research aims to overcome limitations of current techniques by using recent breakthroughs in "programmable DNA self-assembly" to develop protein framework structures that contain "pockets" with tunable size and shape for structural studies. If successful, his efforts will provide a general tool for structural biology and in turn benefit the mechanistic studies and therapeutic development for cancer.




Project Title: "Crystal-free crystallography using programmable 3D DNA crystal frameworks"

Institution: Harvard University

Sponsor(s) / Mentor(s): Peng Yin, PhD

Cancer Type: All cancers, Skin

Research Area: Nanotechnology

Daniel E. Webster, PhD

Daniel E. Webster, PhD

Dr. Webster studies Diffuse Large B Cell Lymphoma (DLBCL), an aggressive cancer that hijacks the normal molecular mechanisms acting in immune B cells to drive malignant growth. Many genes have been studied as oncogenes or tumor suppressors in DLBCL, but a class of long non-coding RNAs (lncRNAs) remains largely unexplored for its function in this cancer. LncRNAs, once thought to be non-functional products of junk DNA, are now known to play an essential role in many biological processes. This research will discover oncogenic or tumor suppressive lncRNAs in DLBCL to better understand the disease and uncover potential targets for cancer diagnosis or therapy.




Project Title: "Identification and analysis of LncRNAs regulating diffuse large B cell lymphoma"

Institution: National Cancer Institute

Sponsor(s) / Mentor(s): Louis M. Staudt, MD, PhD

Cancer Type: Lymphomas

Research Area: Genomics

Tony Yu-Chen Tsai, MD, PhD

Tony Yu-Chen Tsai, MD, PhD

Dr. Tsai [Kenneth G. and Elaine A. Langone Fellow] seeks to understand how the signaling pathway directed by the protein Sonic Hedgehog (Shh) regulates cell-cell adhesion molecules required for correct spatial organization of the neuro-epithelium. Abnormal Shh signaling is associated with several types of cancer, and aberrant regulation of cell-cell adhesion could lead to tumor metastasis. His findings may ultimately lead to understanding and prevention of metastasis in Shh-associated cancers.




Project Title: "Cell sorting in zebrafish neural tube development"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Sean G. Megason, PhD

Cancer Type: All cancers

Research Area: Developmental Biology

Duy P. Nguyen, PhD

Duy P. Nguyen, PhD

Dr. Nguyen [Connie and Bob Lurie Fellow] is analyzing the bacterial enzyme Cas9, which has emerged to be a versatile tool to manipulate the genome. He aims to develop an efficient method for selective delivery to and activation of Cas9 in cancer cells. In addition, the proposed research will explore the possibility of genome manipulation to create genetic models for understanding the mechanistic role of programmed cell death. The developed methodology will hopefully set the foundation for rapidly creating genetic models to interrogate signaling pathways implicated in cancer and to investigate novel drug screening approaches that aim to identify new drug targets for cancer treatment.




Project Title: "Genome editing via an engineered RNA-guided nuclease to create cancer genetic models"

Institution: University of California, San Francisco

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

Cancer Type: All cancers

Research Area: Chemical Biology

Mandy M. Muller, PhD

Mandy M. Muller, PhD

Dr. Muller [HHMI Fellow] is examining Kaposi's sarcoma-associated herpesvirus (KSHV), a virus associated with lifelong infections. A healthy immune system keeps the virus in check; however, in immunocompromised individuals, KSHV is associated with a number of malignances, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). KSHV dramatically manipulates the intracellular gene expression environment of its host cell. The defining characteristic is a near-global depletion of cytoplasmic mRNA called "host shutoff." This process is orchestrated by SOX, a viral enzyme. How SOX is directed to its target mRNAs remains unknown. The goal of this research is to mechanistically delineate how SOX hijacks host factors to dampen gene expression. Her results should reveal key principles governing RNA fate and shed light on how this process is pivotal during oncogenic viral infection.




Project Title: "Widespread RNA destruction and selective preservation during viral infection"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Britt Glaunsinger, PhD

Cancer Type: AIDS-related cancers

Research Area: Virology

Timothy D. Martin, PhD

Timothy D. Martin, PhD

Dr. Martin [Marion Abbe Fellow] focuses on genomic instability, a hallmark of virtually all cancers that underlies the mutations and aneuploidy (incorrect chromosome number) changes that perturb oncogenes and tumor suppressor genes (TSGs). Patient tumor sequencing has unveiled common genomic alterations across different cancers. Recent work described how the cancer genome is shaped by the loss of many genes and gene clusters. Despite the high frequency of TSG mutations and recurrent multi-gene focal deletions in cancer, the relative contribution of TSGs and focal deletions to tumor growth has not yet been compared. The goal of this project is to precisely recreate these genomic alterations and directly test how each contributes to oncogenesis.




Project Title: "Investigating the role of aneuploidy and haploinsufficiency in driving tumorigenesis"

Institution: Brigham and Women's Hospital

Sponsor(s) / Mentor(s): Stephen J. Elledge, PhD

Cancer Type: All cancers, Breast

Research Area: Cancer Genetics

Chao Lu, PhD

Chao Lu, PhD

Dr. Lu [Kandarian Family Fellow] is studying histones, proteins known to fold DNA into high-order structures, which is critical for proper gene expression. Mutations in histones are mutated in certain types of pediatric brain tumors and sarcomas, including a rare bone cancer called chondroblastoma. He aims to understand the biochemical and molecular mechanisms by which histone proteins function and how they are perturbed in tumor cells. This research will provide important insights into the etiology of brain and soft-tissue cancers and identify new approaches for therapeutic targeting.




Project Title: "Understanding the mechanism of histone H3 mutation in cancer initiation and maintenance"

Institution: The Rockefeller University

Sponsor(s) / Mentor(s): C. David Allis, PhD

Cancer Type: Brain, Neuro-oncology, Head and Neck, Sarcomas

Research Area: Chromatin Biology

Yin Liu, PhD

Yin Liu, PhD

Dr. Liu [Layton Family Fellow] studies lung biology. The lung is innervated by diverse types of sensory neurons, collectively called pulmonary sensory neurons. These neurons detect a variety of physiological stimuli from the lung and inform the central nervous system about the state of the lung. Lung cancer, one of the most common cancers with a high rate of lethality, is associated with symptoms such as chronic cough, shortness of breath, and referred cranial facial pain. Her research will examine how pulmonary sensory neurons recognize and respond to lung tumors, and how this tumor sensing influences tumor biology. She aims to understand which populations of pulmonary sensory neurons mediate lung cancer-associated clinical symptoms, how these neurons alter their behaviors in response to tumor growth, and how activating pulmonary sensory pathways affects cancer progression and metastases.




Project Title: "Sensing lung tumors by pulmonary sensory neurons"

Institution: Stanford University

Sponsor(s) / Mentor(s): Mark A. Krasnow, MD, PhD

Cancer Type: Lung

Research Area: Neuroscience

Avinash Khanna, PhD

Avinash Khanna, PhD

Dr. Khanna [Rebecca Ridley Kry Fellow] studies a type of leukemia called mixed lineage leukemia (MLL), which often results in early relapse and a poor prognosis for the patient. A common cause of MLL-mediated cancer development is through dysregulation of gene transcription; however, this process is not well-characterized at the molecular level. Mediator proteins are vital for transforming aberrant cells into malignant cancer. Recently, it was found that inhibition of Mediator proteins diminishes the ability of AML cancer cells to grow and proliferate. This research will use small molecules to elucidate the chemical biology of Mediator proteins, such as downstream changes in transcription, protein-protein binding interactions, and chromosomal localization.




Project Title: "Disrupting the protein-protein interactions of CDK8 to target cancer"

Institution: Harvard University

Sponsor(s) / Mentor(s): Matthew D. Shair, PhD

Cancer Type: Leukemias

Research Area: Medicinal Chemistry

Keren I. Hilgendorf, PhD

Keren I. Hilgendorf, PhD

Dr. Hilgendorf [Layton Family Fellow] is exploring the role of primary cilia in regulating cell proliferation and differentiation. The primary cilium is an antenna-like cellular protrusion that is localized on the apical surface of most vertebrate cells in diverse tissue; it functions in chemo- and mechanosensation. In many cancers, primary cilia are lost so cilia-mediated signaling pathways are deregulated. Understanding the molecular components and functions of ciliary signaling will further our understanding of mechanisms of tumorigenesis and evaluate the importance of primary cilia in cancer.




Project Title: "Role of ciliary IGF-1/AKT signaling in ciliogenesis, adipogenesis, and tissue regeneration"

Institution: Stanford University School of Medicine

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

Cancer Type: All cancers

Research Area: Signal Transduction

Casey A. Gifford, PhD

Casey A. Gifford, PhD

Dr. Gifford [HHMI Fellow] aims to identify and define the roles for DNA binding proteins that can manipulate DNA conformation in the nucleus. DNA is maintained in an ordered conformation that contributes to control of gene expression and cellular identity. She will employ next-generation sequencing approaches and human induced pluripotent stem cells to better understand the mechanisms of this process. Her goal is to understand why the loss of function or aberrant expression of these DNA binding proteins leads to cancer.




Project Title: "Dissecting the role of pioneer transcription factors in cancer progression"

Institution: Gladstone Institutes

Sponsor(s) / Mentor(s): Deepak Srivastava, MD

Cancer Type: All cancers, Lymphomas

Research Area: Chromatin Biology

Dennis L. Buckley, PhD

Dennis L. Buckley, PhD

Dr. Buckley [Merck Fellow] aims to develop improved inhibitors of BET-bromodomain proteins for treatment of multiple cancers, such as NUT-midline carcinoma, acute leukemia, hematological malignancies and solid tumors. His goal is to chemically generate drugs with improved efficacy or lower side effects. In addition, he will evaluate both novel and existing BET inhibitors in neuroblastoma, which preliminary data suggests is sensitive to BET inhibition.




Project Title: "Development of selective brodomain inhibitors from dual brodomain-kinase inhibitors for the treatment of neuroblastoma"

Institution: Dana-Farber Cancer Institute

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

Cancer Type: All cancers, Neuroendocrine

Research Area: Medicinal Chemistry

Neel H. Shah, PhD

Neel H. Shah, PhD

Dr. Shah aims to elucidate structural details of the signaling enzyme ZAP-70, found primarily in immune T cells. Expression of ZAP-70 in other immune cells, B cells, however, is associated with chronic lymphocytic leukemia. Furthermore, loss of ZAP-70 function causes severe combined immunodeficiency; an impaired immune system can increase a patient's susceptibility to tumor development. His research on ZAP-70 structure and function will help understand how this enzyme differs from related signaling enzymes, thereby laying the groundwork for the development of ZAP-70-specific therapeutics.




Project Title: "Interrogating ZAP-70 substrate recognition using high-throughput mutant screening"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): John Kuriyan, PhD

Cancer Type: Leukemias

Research Area: Structural Biology

Hume Akahori Stroud, PhD

Hume Akahori Stroud, PhD

Dr. Stroud [HHMI Fellow] is examining the distinct role of MeCP2, a protein that binds methyl-CpG-DNA and regulates neuronal chromatin, which "packages" DNA. The proposed research has significant implications for causes and mechanisms of cancer, as dysregulation of DNA methylation and other chromatin modifications represent early oncogenic events in a wide range of human cancers. His project may have particular relevance to cancers of the nervous system.




Project Title: "Understanding the mechanism and roles of changes in chromatin composition in the brain"

Institution: Harvard Medical School

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

Cancer Type: All cancers, Brain, Neuro-oncology

Research Area: Neuroscience

Eirini P. Papapetrou, MD, PhD

Eirini P. Papapetrou, MD, PhD

Dr. Papapetrou studies a disease called myelodysplastic syndrome (MDS), which often progresses to leukemia. She is using a novel approach to identify the specific genetic alterations involved in the development of MDS, which are not currently known.
She aims to understand how tumor suppressor genes can promote cancer through a type of genetic state called “haploinsufficiency.” By reprogramming human pluripotent stem cells to harbor specific deletions in their chromosomes, she seeks to characterize novel genetic causes of MDS. This approach could be a model for uncovering genetic mechanisms of other cancers as well.




Project Title: "Dissecting chromosome hemizygosity with human pluripotent stem cells"

Institution: Icahn School of Medicine at Mount Sinai

Sponsor(s) / Mentor(s):

Cancer Type: All cancers, Leukemias

Research Area: Cancer Genetics

Matthew P. Miller, PhD

Matthew P. Miller, PhD

Dr. Miller [HHMI Fellow] is investigating how cells ensure the correct partitioning of genetic material during cell division. Errors in this process occur in nearly all tumor cells and are the leading cause of miscarriages and congenital birth defects in humans. He is using novel techniques to isolate and examine the physical binding properties of the molecules that mediate this process. The goal of his work is to determine the molecular mechanisms that direct genome partitioning during cell division and understand how this process occurs with a high level of fidelity in normal cells, yet is error-prone during tumorigenesis.




Project Title: "Regulation of kinetochore assembly"

Institution: Fred Hutchinson Cancer Research Center

Sponsor(s) / Mentor(s): Susan Biggins, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Rohan K. Srivas, PhD

Rohan K. Srivas, PhD

Dr. Srivas is studying the changes in the composition and function of bacteria inhabiting the human gut (microbiome). The microbiome plays an extensive role in modulating host metabolism and inflammation, which when disrupted can lead to diseases such as cancer. There has been much interest in understanding this relationship between the microbiome and human cancers. By tracking changes in the gut microbiome of patients undergoing drastic weight loss, this research will map the dynamics of host-microbiome connections, potentially highlighting strategies for modifying the microbiome to treat metabolic disorders and reduce the risk of gastric and colon cancers.




Project Title: "Longitudinal profiling of host-microbiome interactions in obese patients during drastic weight loss"

Institution: Stanford University School of Medicine

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

Cancer Type: All cancers

Research Area: Systems Biology

Antoine Molaro, PhD

Antoine Molaro, PhD

Dr. Molaro studies how an ancient “evolutionary arms race” between Krab-Zinc-Finger genes (KZNFs) and DNA sequence elements called retrotransposons has shaped transcriptional networks of stem cells and pluripotency. Because many cancers dedifferentiate to a stem cell-like state, refined knowledge about how KZNFs act to finely modulate transcriptional control may prove essential for the development of new cancer drugs.




Project Title: "Evolutionary and functional consequences of genetic conflicts between KRAB-Zinc-Fingers and endogenous retroviruses in primate genomes"

Institution: Fred Hutchinson Cancer Research Center

Sponsor(s) / Mentor(s): Harmit S. Malik, PhD

Cancer Type: All cancers

Research Area: Evolution

Erin F. Simonds, PhD

Erin F. Simonds, PhD

Dr. Simonds is investigating tumor-initiating cells in pediatric glioblastoma, a type of brain tumor. This rare subpopulation of cells has the unique capacity to re-establish the tumor after therapy, and is therefore a critical therapeutic target. He is using a technique called mass cytometry to determine how these cells respond to communication signals from their environment. The goal of this work is to identify drugs that specifically kill tumor-initiating cells by blocking the signaling networks that sustain their survival.




Project Title: "Single-cell analysis and targeting of signaling networks in glioblastoma tumor-initiating cells"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): William A. Weiss, MD, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: Stem Cell Biology

Thomas S. Vierbuchen, PhD

Thomas S. Vierbuchen, PhD

Dr. Vierbuchen [HHMI Fellow] aims to understand how neurons adapt to experience by modifying the complement of genes they express. He is using high-throughput sequencing-based approaches to identify and characterize the function of genomic regulatory elements that control neuronal activity-regulated gene transcription.




Project Title: "Understanding the developmental programming and function of the enhancers that control activity-regulated transcription in the mammalian cortex"

Institution: Harvard Medical School

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

Cancer Type: All cancers

Research Area: Developmental Neurobiology

Costas A. Lyssiotis, PhD

Costas A. Lyssiotis, PhD

Dr. Lyssiotis is studying the effects of oncogenes on 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 signaling 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: Weill Medical College of Cornell University

Sponsor(s) / Mentor(s):

Cancer Type: Pancreatic

Research Area: Biochemistry

Sean C. Bendall, PhD

Sean C. Bendall, PhD

Dr. Bendall is using novel single-cell analysis techniques to investigate how normal regulatory cell signaling networks are rewired, allowing cancer to grow unchecked. He has applied this technology to examine healthy human blood cells, measuring multiple parameters simultaneously in single cells. Collectively, such single-cell analyses provide an unprecedented opportunity to identify novel regulators (such as drugs, genes, and protein modifications) of cell development and identity, as well as provide insight into how these regulators interact with genes and mutations that promote cancer cell transformation. His goal is to use these studies 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):

Cancer Type: Leukemias

Research Area: Proteomics

Moritz F. Kircher, MD, PhD

Moritz F. Kircher, MD, PhD

Dr. Kircher’s goal is to develop a new nanoparticle-based technology that will allow the detection and treatment of cancer based on in vivo tumor marker expression profiling. This would enable a single cancer cell to be both imaged and killed in a single process. To date this has not been achieved, in part due to inadequate sensitivity and inability to accurately visualize the expression of multiple tumor markers simultaneously. 
A radiologist by training, he has developed a new generation of Raman-MRI nanoparticles, resulting in unprecedented sensitivity and targeted signal specificity. He will work with prostate, pancreatic and breast cancer tumors to develop markers that can be targeted by these nanoparticles. If successful, this approach will have far-reaching implications for cancer detection and image-guided therapy.




Project Title: "Raman-MRI nanobeacons: towards a universal cancer theranostic agent"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Imaging

Xiaolin Nan, PhD

Xiaolin Nan, PhD

Understanding molecular function in biological settings is essential for successful development of targeted therapies for cancer. Advances in biochemical profiling techniques have generated lists of molecules involved in cancer development and progression, but the mechanisms by which these molecules work together within cells and tumors remain largely unclear. Molecularly targeted cancer therapeutics based on incomplete understanding of the tumorigenic mechanisms often demonstrate initial response followed by cancer resistance.
Drs. Nan and Gibbs, both biochemical engineers, will work as a team to address this problem using a revolutionary high-resolution microscopy technique to visualize—at the molecular level—the interactions of an array of proteins involved in the HER2 cell signaling pathway implicated in breast cancer within tumor cells, and their response to therapeutic agents such as Herceptin. They anticipate the findings of this work will significantly improve our understanding of the spatial and temporal organization of cancer cell signaling, enabling development of more effective targeted cancer therapeutics with lasting response.




Project Title: "Studying spatial regulation of HER2 tumorigenesis with multispectral super resolution microscopy (MSSRM)"

Institution: Oregon Health & Science University

Sponsor(s) / Mentor(s):

Cancer Type: Breast

Research Area: Imaging

Emily P. Balskus, PhD

Emily P. Balskus, PhD

Humans live in symbiosis with trillions of microbes, and there is growing evidence that these organisms can impact the development and progression of cancer.
Dr. Balskus’ research seeks to elucidate the mechanisms by which molecules produced by microbes inhabiting the human gut influence the development and progression of colorectal cancer. She will combine tools from synthetic chemistry, biochemistry, and microbiology to both characterize and block harmful microbial processes. This work will impact our understanding of how the gut environment influences carcinogenesis, ultimately leading to new strategies for cancer prevention and treatment.




Project Title: "Understanding and preventing carcinogenesis caused by the human microbiota”"

Institution: Harvard University

Sponsor(s) / Mentor(s):

Cancer Type: Colorectal

Research Area: Chemical Biology

Arvin C. Dar, PhD

Arvin C. Dar, PhD

Genes that are mutated, amplified, or altered in cancer contribute directly to tumor development, maintenance, and metastasis. The Ras-MAPK signaling pathway contains two of the most frequently altered genes across all cancers. Ras-MAPK has important roles in normal development but is also commonly dysregulated in a variety of human cancers. The biochemistry of this pathway is highly complex, thus hampering drug development efforts and resulting in the inability to develop any drug that directly targets Ras-MAPK to date.  
Dr. Dar is using two novel approaches to better understand the Ras-MAPK pathway. First, he is reconstructing the pathway from its individual parts, much like an engineer will construct a circuit from relatively simple components. Second, he is developing chemical tools that can perturb functional Ras-MAPK networks in the cell. Both approaches will allow him to investigate questions about how this network functions and how its dysregulation contributes to disease. Ultimately, his goal is to create new drugs that precisely disable the Ras-MAPK pathway in cancer.




Project Title: "Targeting allosteric control in the Ras-MAPK pathway for cancer therapy"

Institution: Icahn School of Medicine at Mount Sinai

Sponsor(s) / Mentor(s):

Cancer Type: Pancreatic

Research Area: Chemical Biology

Summer L. Gibbs, PhD

Summer L. Gibbs, PhD

Understanding molecular function in biological settings is essential for successful development of targeted therapies for cancer. Advances in biochemical profiling techniques have generated lists of molecules involved in cancer development and progression, but the mechanisms by which these molecules work together within cells and tumors remain largely unclear. Molecularly targeted cancer therapeutics based on incomplete understanding of the tumorigenic mechanisms often demonstrate initial response followed by cancer resistance.
Drs. Gibbs and Nan, both biochemical engineers, will work as a team to address this problem using a revolutionary high-resolution microscopy technique to visualize—at the molecular level—the interactions of an array of proteins involved in the HER2 cell signaling pathway implicated in breast cancer within tumor cells, and their response to therapeutic agents such as Herceptin. They anticipate the findings of this work will significantly improve our understanding of the spatial and temporal organization of cancer cell signaling, enabling development of more effective targeted cancer therapeutics with lasting response.




Project Title: "Studying spatial regulation of HER2 tumorigenesis with multispectral super resolution microscopy (MSSRM)"

Institution: Oregon Health & Science University

Sponsor(s) / Mentor(s):

Cancer Type: Breast

Research Area: Imaging

Raymond E. Moellering, PhD

Raymond E. Moellering, PhD

Dr. Moellering is interested in understanding the link between alteration of metabolic pathways and corresponding protein modifications that occur in cancer cells. In addition, he is investigating whether cancer cells use small molecule signaling, known as quorum-sensing, to communicate and thus control tumor initiation, growth and metastasis. His goal is to provide insights into many aspects of tumor progression and to potentially identify new opportunities for therapeutic intervention.

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

Institution: Scripps Research Institute

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Chemical Biology

Alexey A. Soshnev, MD, PhD

Alexey A. Soshnev, MD, PhD

Dr. Soshnev [HHMI Fellow] studies how genetic information is packaged in the nucleus and how such packaging is interpreted by the cellular machinery. Changes in nuclear architecture may simultaneously affect the function of thousands of genes and are a hallmark of cancer. This research focuses on a family of small nuclear proteins termed “linker histones,” which are thought to orchestrate higher-order folding of DNA in the nucleus. Understanding the molecular connection between the nuclear architecture and gene regulation will shed new light on the processes underlying oncogenic transformation.




Project Title: "The study of linker histone H1 in transcriptional regulation and genome organization"

Institution: The Rockefeller University

Sponsor(s) / Mentor(s): C. David Allis, PhD

Cancer Type: All cancers

Research Area: Chromatin Biology

Shruti Naik, PhD

Shruti Naik, PhD

Dr. Naik is studying the interactions between immune cells and adult skin tissue stem cells in an effort to understand the how this crosstalk drives epithelial disorders, including chronic inflammation and cancer. Because adult tissue stem cells are long-lived cells that continually replenish tissues throughout an organism’s lifetime, they represent ideal points of therapeutic intervention. Identification of inflammation-induced molecular changes in skin stem cells that drive epithelial dysfunction will facilitate the development of therapies for various epithelial inflammatory diseases and cancer.




Project Title: "Immune and epidermal stem cell cross talk in skin inflammation"

Institution: The Rockefeller University

Sponsor(s) / Mentor(s): Elaine V. Fuchs, PhD

Cancer Type: Skin

Research Area: Stem Cell Biology

Ankur Jain, PhD

Ankur Jain, PhD

Dr. Jain focuses on understanding how the level of mRNA species in the cell is regulated. Disruption of these regulatory processes can lead to cancer initiation and progression. These processes are carried out at discrete cytoplasmic non-membrane bound organelles called processing bodies (P-bodies). He aims to develop a molecular understanding of P-body architecture, assembly rules, and their role in gene regulation.




Project Title: "Formation and function of mRNA processing bodies"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Ronald D. Vale, PhD

Cancer Type: All cancers

Research Area: RNA

Gabriela C. Monsalve, PhD

Gabriela C. Monsalve, PhD

Dr. Monsalve [Robert Black Fellow] is studying glucocorticoids (GCs), naturally occurring steroid hormones that can be used therapeutically to kill certain tumor cells. Aggressive blood cancers like lymphomas and leukemias are commonly treated with chemotherapy drugs, including GCs. Unfortunately, some patients do not respond to GCs, which usually indicates a poor likelihood of survival. To improve the treatment of patients with GC-resistant cancers, and to better understand how GCs destroy cancerous cells, she aims to understand how and where they are absorbed in the body.  Examining how the absorption occurs will both illuminate how these hormones destroy tumor cells and support the future development of treatment options for patients with resistant cancers. 




Project Title: "Identification and characterization of plasma membrane transporters for glucocorticoids"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Keith R. Yamamoto, PhD

Cancer Type: Breast, Lymphomas, Prostate

Research Area: Endocrinology

Chenxi Tian, PhD

Chenxi Tian, PhD

Dr. Tian [Sherry and Alan Leventhal Family Fellow] studies pancreatic ductal adenocarcinoma (PDAC). PDAC is characterized by an extremely stiff texture, which is caused by accumulation of excessive extracellular matrix (ECM). The compositions of ECM, known to have major effects on tumor progression, are not well understood in PDAC disease. She aims to identify global ECM changes during PDAC progression by proteomic approaches, and to investigate how these changes impact cancer progression. The uncovered ECM of PDAC will provide novel insights into diagnosis, prognosis and treatments of this very difficult disease.




Project Title: "Understanding the roles of extracellular matrix proteins in pancreatic ductal adenocarcinoma progression"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s): Richard O. Hynes, PhD

Cancer Type: Pancreatic

Research Area: Invasion and Metastasis

Liron Bar-Peled, PhD

Liron Bar-Peled, PhD

Dr. Bar-Peled [Lallage Feazel Wall Fellow] is exploring how the protease Caspase-8 regulates T cell activation, which represents a critical step in the adaptive immune response to cancer. While Caspase-8 has long been appreciated to be essential for T cell activation, the molecular mechanisms underlying its role in this process remain poorly understood. His work will focus on identifying and characterizing the proteins cleaved by Caspase-8, which may provide additional therapeutic avenues to activate T cells to target malignant cells in cancer patients.




Project Title: "Proteolytic regulation of the adaptive immune response: identification of caspase-8 substrates required for T cell activation"

Institution: The Scripps Research Institute

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

Cancer Type: All cancers

Research Area: Chemical Biology

Eric M. Woerly, PhD

Eric M. Woerly, PhD

Dr. Woerly [Suzanne and Bob Wright Fellow] aims to develop new chemical synthetic methods for the preparation of cancer therapeutics. The introduction of fluorine into pharmaceutical targets is an important element of drug design. The controlled, selective synthesis of fluorinated compounds, however, can be a great synthetic challenge. He plans to enable access to such targets by developing a method for the asymmetric synthesis of fluorinated small molecules, potentially leading to improved cancer therapies.




Project Title: "Accessing new cancer therapeutics via an intermolecular fluorofunctionalization reaction"

Institution: Harvard University

Sponsor(s) / Mentor(s): Eric N. Jacobsen, PhD

Cancer Type: All cancers

Research Area: Organic Chemistry

Hanjing Peng, PhD

Hanjing Peng, PhD

Dr. Peng seeks to identify compounds that inhibit the proteasome, the protein degradation machinery in the cell that maintains the balance of cell growth and death. Inhibitors that regulate proteasome function are potential anticancer drugs. Inspired by the functional mechanism of a class of natural products that includes FK506 and rapamycin, she has designed and constructed a synthetic library of compounds (macrocyclic “rapafucin”) in search of potent proteasome inhibitors. She hopes to discover new anticancer drug candidates with lower toxicity or side effects than current drugs.




Project Title: "Targeting the proteasome using a hybrid, combinatorial rapafucin library"

Institution: The Johns Hopkins University

Sponsor(s) / Mentor(s): Jun O. Liu, PhD

Cancer Type: Leukemias, Myeloma

Research Area: Drug Discovery

Ryan D. Baldridge, PhD

Ryan D. Baldridge, PhD

Dr. Baldridge [Fraternal Order of Eagles Fellow] focuses on a cellular process called endoplasmic reticulum associated degradation (ERAD), a system involved in recognition, transport and degradation of regulated and misfolded proteins. ERAD plays a role in cancer processes, in some instances by regulating the levels of proteins involved in tumor growth and metastasis. In other cases ERAD is upregulated to relieve ER stress caused by tumor growth. His goal is to understand how the ERAD system recognizes target proteins at the ER, transports them across the ER membrane to the cytosol, and ubiquitinates them prior to proteasomal degradation.




Project Title: "Investigating the mechanism of retro-translocation by ERAD"

Institution: Harvard Medical School

Sponsor(s) / Mentor(s): Thomas A. Rapaport, PhD

Cancer Type: All cancers

Research Area: Biochemistry

Brittany Adamson, PhD

Brittany Adamson, PhD

Dr. Adamson [HHMI Fellow] is using large-scale genetic approaches to map the regulatory networks responsible for maintaining molecular equilibria inside human cells. An important question in cancer research is how cancer cells adapt to abnormal growth environments and proliferate under stress. Systematic characterization of the processes that maintain these equilibria will be critical for better understanding cancer formation and growth.




Project Title: "Comprehensive characterization of the integrated networks that regulate protein homeostasis within the mammalian endoplasmic reticulum"

Institution: University of California, San Francisco

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

Cancer Type: All cancers, Myeloma, Sarcomas

Research Area: Protein Processing

Nathan D. Thomsen, PhD

Nathan D. Thomsen, PhD

Dr. Thomsen is studying the molecular interactions that are required for specific signaling pathways in the cell. In cancer cells, these signaling pathways are often disrupted or misregulated. Using sophisticated new techniques he has developed, he will "capture and trap" proteins in real time, as they are signaling-similar to a video freeze-frame. He plans to then engineer antibodies that will specifically target and inhibit these pathways, which can be used to learn more about the molecular mechanisms underlying signaling and may eventually be developed into therapeutics for cancer and other diseases.




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

Institution: UC, San Francisco

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Chemical Biology

Jakob von Moltke, PhD

Jakob von Moltke, PhD

Dr. von Moltke [HHMI Fellow] studies how the immune system detects bacteria and parasitic worms. Emerging evidence suggests that these same immune cells also respond to tissue damage in the absence of infection, suggesting an evolutionary role in wound healing. He is examining how these cells are regulated during wound healing and how their activity contributes to tissue regeneration and repair. Since tumors regularly hijack the body’s natural wound healing processes, his findings should provide insight into tumorigenesis and could suggest novel therapeutic strategies.




Project Title: "Innate type II cells and wound healing"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Richard Locksley, MD

Cancer Type: All cancers, Skin

Research Area: Basic Immunology

Victoria E.H. Wang, MD, PhD

Victoria E.H. Wang, MD, PhD

Dr. Wang seeks to understand the mechanisms by which tumor cells become resistant to drug therapy and spread to distant organs. She is utilizing functional genomics tools to identify novel pathways modulating these processes in the hope of developing new therapies to augment treatment response in cancer patients. 




Project Title: "The role of the c-Met/Hepatocyte growth factor (HGF) pathway in drug resistance and tumor metastasis"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Frank McCormick, PhD

Cancer Type: All cancers, Gastric, Lung

Research Area: Chemoresistance

Steven Lin, PhD

Steven Lin, PhD

Dr. Lin [HHMI Fellow] investigates the molecular mechanism by which the bacterial enzyme Cas9 targets and cleaves double-stranded DNA. His goal is to provide a detailed understanding of Cas9 mechanism and structure, ultimately aiming to develop Cas9 into a versatile genome engineering tool for further studies of cancer-associated genes.




Project Title: "Molecular mechanism of Cas9, an RNA-guided DNA endonuclease"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Jennifer A. Doudna, PhD

Cancer Type: All cancers

Research Area: Biochemistry

Christine Iok In Chio, PhD

Christine Iok In  Chio, PhD

Dr. Chio [Shirley Stein Fellow] works on pancreatic cancer, which is a particularly devastating and difficult-to-treat disease because of its ability to grow in conditions of high oxidative stress—conditions in which normal cells would not survive. She is evaluating the biological role of oxidative stress in pancreatic cancer development and progression, using both mouse models of pancreatic cancer as well as human tumor samples. Her work may result in a novel therapeutic approach for this disease. 




Project Title: "Regulation of the global redox landscape: Investigating the role of Nrf2 in pancreatic cancer development"

Institution: Cold Spring Harbor Laboratory

Sponsor(s) / Mentor(s): David A. Tuveson, MD, PhD

Cancer Type: Pancreatic

Research Area: Cancer Genetics

Mary Williard Elting, PhD

Mary Williard Elting, PhD

Dr. Elting studies the mechanics of cell division, with the goal of understanding how cells accurately transmit one copy of their genetic information into each of two daughter cells. Mistakes in this process are implicated in cancer, as well as birth defects and miscarriage. She will mechanically disrupt dividing cells and then detect how these perturbations affect the forces generated during division.




Project Title: "Probing how kinetochore-fibers anchor to spindles to robustly and accurately segregate chromosomes"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Sophie Dumont, PhD

Cancer Type: All cancers, Breast

Research Area: Cell Biology

Kenneth Chen, MD

Kenneth Chen, MD

Dr. Chen studies Wilms tumor, a pediatric kidney cancer that is the fourth most common childhood cancer. Wilms tumor is treated with a combination of surgery, chemotherapy, and radiation; although outcomes have dramatically improved over the decades, they remain poor for children with high-risk disease. His preliminary research has identified a subset of Wilms tumors with dysregulated expression of microRNAs, a type of short noncoding RNA that regulates protein production. He will study how this dysregulation causes cancer in children and aims to use this information to develop a novel therapeutic strategy for these tumors.




Project Title: "Dysregulation of the N-myc/Lin28/let-7 axis in childhood Wilms tumors"

Institution: UT Southwestern Medical Center

Sponsor(s) / Mentor(s): James F. Amatruda, MD, PhD

Cancer Type: Wilm’s Tumor

Research Area: RNA

Michael A. Cianfrocco, PhD

Michael A. Cianfrocco, PhD

Dr. Cianfrocco [HHMI Fellow] studies proteins called dynactin and dynein that function to transport organelles within the cell, a process that is particularly important during cell division. He aims to elucidate the structural basis for dynactin's ability to regulate dynein activity. Since many viruses, including cancer-causing oncoviruses, require dynein to be transported from the cell membrane to the nucleus for genome replication, understanding the molecular details of dynein-dynactin function may provide novel targets for cancer therapies.




Project Title: "How does dynein achieve processivity?"

Institution: Harvard University

Sponsor(s) / Mentor(s): Andres Leschziner, PhD & Samara L. Reck-Peterson, PhD

Cancer Type: Gynecological, Liver

Research Area: Structural Biology

Omar Abdel-Wahab, MD

Omar Abdel-Wahab, MD

Dr. Abdel-Wahab [Edward P. Evans Foundation Clinical Investigator] specializes in specific blood cancers called myelodysplastic syndrome (MDS) and acute myelogenous  leukemia (AML). He recently identified mutations in the gene ASXL1 in patients with MDS and AML. ASXL1 is one of the most commonly mutated genes in MDS patients, and these mutations occur in up to 20% of AML patients. ASXL1 mutations result in a worsened overall survival in MDS and AML patients and contribute to chemotherapy resistance in AML. However, exactly how these mutations contribute to leukemia development remains unknown. He has demonstrated that loss of ASXL1 results in increased expression of genes that are known to promote development of AML. Preliminary data suggests that ASXL1 regulates expression of key genes by affecting proteins called histones. In a mouse model, loss of ASXL1 alone results in a phenotype remarkably similar to human MDS. Moreover, when ASXL1 loss is combined with other genes known to promote chronic leukemia in mice, an acute leukemia develops that hastens death of the mice. His overall goal is to gain a more thorough understanding of ASXL1 function and to ultimately test approved as well as novel targeted therapeutics for treatment of MDS and AML.

 




Project Title: "Understanding and targeting altered histone modifiers in the myeloid malignancies"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Ross L. Levine, MD

Cancer Type: Leukemias

Research Area: Cancer Genetics

Tracy T. Chow, PhD

Tracy T. Chow, PhD

Dr. Chow studies the molecular basis of how cancer cells maintain the ability to divide indefinitely. In most human cancers, an enzyme named telomerase is crucial in maintaining chromosomal ends (or telomeres) to achieve immortality. She is exploring a novel mechanism for telomere maintenance, which could advance the development of improved therapeutics for glioblastoma and other cancers.




Project Title: "Investigating and engineering non-canonical telomere maintenance mechanisms in human cells"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Elizabeth H. Blackburn, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Xiaoxiao Shawn Liu, PhD

Xiaoxiao Shawn Liu, PhD

The methylation status of DNA influences many biological processes during mammalian development, and is known to be highly aberrant in cancers including pancreatic cancer. DNA demethylation is mediated by a group of enzymes, TET (ten-eleven translocation) dioxygenases. Mutations of TET genes are frequently identifed in cancers. My project is to evaluate the significance of Tet proteins in pancreatic cancer, and will provide a basis for therapeutic modulation of TET enzymes to prevent and block malignant growth.




Project Title: "The role of Tet proteins in pancreatic cancer"

Institution: Whitehead Institute for Biomedical Research

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

Cancer Type: All cancers, Pancreatic

Research Area: Signal Transduction

Jessica P. Lao, PhD

Jessica P. Lao, PhD

Dr. Lao studies protein turnover, a process that is essential for cellular homeostasis. Ubiquitin ligases are enzymes that regulate protein turnover by facilitating the attachment of the small molecule ubiquitin to proteins, which targets them for destruction. Mutations in the CRL3 ligases are associated with many types of cancer. She aims to identify novel targets of CRL3 ligases to understand how they regulate cellular processes. This will shed light on the underlying causes of CRL3-associated cancer and provide avenues for developing new therapeutic interventions.




Project Title: "Identifying substrates of the mammalian Cullin3-RING E3 ligases"

Institution: University of California, San Francisco

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

Cancer Type: All cancers

Research Area: Biochemistry

Justin M. Crest, PhD

Justin M. Crest, PhD

Dr. Crest is studying the mechanical forces between cells and their underlying substrate, or extracellular matrix (ECM). The physical properties of cells and the ECM shape tissues during development and are critical for malignant tumor progression and metastasis. His research will determine which molecules generate and balance the mechanical forces involved in migration and tissue formation and thus identify novel mechanisms of malignancy.




Project Title: "Cells, ECM, and the mechanical forces that regulate organ shape"

Institution: University of California, Berkeley

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

Cancer Type: All cancers

Research Area: Cell Biology

Eric L. Van Nostrand, PhD

Eric L. Van Nostrand, PhD

Dr. Van Nostrand [Merck Fellow] aims to understand how alterations in RNA processing can lead to cancer development and progression. He will identify RNA processing factors that drive medulloblastoma brain tumor growth and proliferation, and use genomics techniques to profile their regulatory targets. This network will both serve as a tool for understanding basic mechanisms of neuronal and medulloblastoma development and progression, and a means to identify critical modulators of tumor development that can serve as targets for future therapeutics.




Project Title: "Identification and analysis of functionally relevant RNA binding protein regulatory networks in medulloblastoma"

Institution: University of California, San Diego

Sponsor(s) / Mentor(s): Eugene Yeo, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: RNA

Alex Pollen, PhD

Alex Pollen, PhD

Dr. Pollen is using comparative genomics, single cell gene expression, and stem cell biology approaches to study genes uniquely expressed in human neural stem cells. Because the development of the human brain involves many of the same processes – increased proliferation, migration, and angiogenesis – that become dysregulated in brain tumors, these genes with specific neural stem cell expression may serve as therapeutic targets and diagnostic markers of brain tumor stem cells that initiate glioblastoma and other cancers.




Project Title: "Regulation of proliferation, migration and angiogenesis by genes uniquely expressed in human neural stem cells"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Arnold R. Kriegstein, MD, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: Developmental Neurobiology

Shuibin Lin, PhD

Shuibin Lin, PhD

Dr. Lin studies neuroblastoma cancers. Genetic amplification and aberrant expression of the oncogenes LIN28B and MYCN are associated with high-risk neuroblastoma and poor survival. Interestingly, these genes positively regulate each other and form a self-reinforcing feedback loop to drive neuroblastoma oncogenesis. His research aims to identify novel factors that interact with LIN28B/MYCN in tumor formation. He is characterizing a LIN28B-interacting long intergenic non-coding RNA (lincRNA) and will determine how the lincRNA functions to regulate neuroblastoma progression.




Project Title: "Molecular and cellular characterization of a novel LincRNA in neuroblastoma"

Institution: Boston Children's Hospital

Sponsor(s) / Mentor(s): Richard Gregory, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: Carcinogenesis

Shreeram Akilesh, MD, PhD

Shreeram Akilesh, MD, PhD

Dr. Akilesh focuses on regions of the genome previously thought to be “junk DNA.” Recent studies demonstrate that they in fact contain motifs that serve a vital function in regulation of many genes. Using next-generation sequencing strategies and advanced bioinformatics analyses, he will study the reprogramming of regulatory DNA regions as normal kidney tissues transform into cancers. This research will provide insights into the genomic regulation of kidney cancer that could be used to develop more effective treatments.




Project Title: "Regulatory genomics of kidney cancers"

Institution: University of Washington

Sponsor(s) / Mentor(s): John A. Stamatoyannopoulos, MD

Cancer Type: Kidney, Wilm’s Tumor

Research Area: Epigenetics

Beverly J. Piggott, PhD

Beverly J. Piggott, PhD

Dr. Piggott [Lefkofsky Family Fellow] is exploring the role of ion channels in brain cancer. Ion channels function as a “gate” to regulate the movement of ions (such as sodium and potassium) into and out of the cell.  They are essential for proper cell growth and signaling in normal cells, and misregulation or mutations in ion channels have been linked to cancer cell proliferation and metastasis. Her goal is to obtain mechanistic insight into the function of ion channels in brain tumors, which may provide new targets for diagnosis and therapeutic intervention.




Project Title: "Brain tumor suppression by mutation(s) of the voltage-gated sodium channel Para"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Yuh Nung-Jan, PhD

Cancer Type: Brain, Neuro-oncology

Research Area: Developmental Neurobiology

Amit J. Sabnis, MD

Amit J. Sabnis, MD

Dr. Sabnis is exploring novel treatment options for rhabdomyosarcomas, the most common pediatric soft tissue sarcomas. These sarcomas uniquely depend on the activity of “protein chaperones” that prevent newly made proteins from forming toxic clumps. His research focuses on small molecules that inhibit one class of chaperones called HSP70s. The goal of these studies is to identify a new target for drug development to help cure this disease.




Project Title: "Exploiting chaperone dependence as a novel therapeutic strategy in alveolar rhabdomyosarcoma"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Trever G. Bivona, MD, PhD

Cancer Type: Sarcomas

Research Area: Experimental Therapeutics

Scott Haihua Chu, PhD

Scott Haihua Chu, PhD

Dr. Chu focuses on a promising new class of therapy that inhibits epigenetic regulators, proteins that control the expression and activity of genes through DNA sequence-independent chemical modifications. Much remains unknown about how these new drugs induce specific changes in tumors upon treatment or what their efficacy is in sustaining long-term, durable responses in patients. He plans to characterize the changes induced with the use of such inhibitors in animal and human models of leukemia. These studies may serve as a proof of principle for the broader use of epigenetic inhibitors as a part of cancer therapy.




Project Title: "The role of DOT1L in pediatric leukemias"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Scott A. Armstrong, MD, PhD

Cancer Type: Leukemias

Research Area: Epigenetics

Jens C. Schmidt, PhD

Jens C. Schmidt, PhD

Dr. Schmidt [Merck Fellow] focuses on understanding how the enzyme telomerase maintains the length of the ends of human chromosomes. This process is crucial to prevent chromosome fusion events, a strong driving force of cancer. In addition, 90% of all cancers require telomerase activity for survival, making it a potential target for cancer therapy. He will use a combination of biophysical, biochemical and cell biological approaches to elucidate how telomerase is recruited to chromosome ends and to identify potential inhibitors of this process.




Project Title: "Single-molecule analysis of telomerase recruitment to telomeres"

Institution: University of Colorado

Sponsor(s) / Mentor(s): Thomas R. Cech, PhD

Cancer Type: All cancers

Research Area: Biochemistry

Wenwen Fang, PhD

Wenwen Fang, PhD

Dr. Fang [HHMI Fellow] aims to understand the mechanism and regulation of microRNA biogenesis. MicroRNAs function to regulate gene expression and their disruption contributes to the initiation and progression of cancer. She will combine high-throughput sequencing techniques and biochemistry to examine the recognition and processing of microRNA precursors, which may ultimately contribute to more effective cancer diagnosis and therapy.




Project Title: "Mechanism and regulation of primary-microRNA processing"

Institution: Whitehead Institute for Biomedical Research

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

Cancer Type: All cancers

Research Area: RNA

Andrew R. Nager, PhD

Andrew R. Nager, PhD

Dr. Nager [Fayez Sarofim Fellow] is studying the primary cilium, an organelle that cells use to sense the environment and communicate with other cells. To do so, the primary cilium selectively exchanges signaling molecules with the cell body. He is using cell biology, biochemistry, and biophysics to understand the gate between the primary cilium and the cell body. Because dysfunctions of the primary cilium promote cancer and cause developmental disease, this research is an important new avenue of exploration.




Project Title: "Dissecting the mechanism of selective diffusion into the primary cilium"

Institution: Stanford University School of Medicine

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

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

Research Area: Cell Biology

Cameron J. Turtle, MD, PhD

Cameron J. Turtle, MD, PhD

Hematopoietic stem cell transplantation (HCT) is a potentially curative procedure for patients with hematologic malignancies who are otherwise incurable with conventional therapies. Despite advances in post-transplant care, the morbidity and mortality of complications such as graft versus host disease (GVHD) and infections remain significant limitations, and hinder the application of this life-saving procedure. Infection and GVHD are influenced by the immune system, which in turn is regulated by the bacterial contents of the human gastrointestinal tract.
Dr. Turtle will test the hypotheses that alterations in the bacterial composition of the human gastrointestinal tract regulate the reconstitution of a specialized bacteria-responsive subset of immune cells after HCT, and that impaired regulation of this immune cell subset is associated with an increased risk of infection or GVHD.




Project Title: "The impact of the colonic microbiota on reconstitution of CD161hi cells and clinical outcomes after allogeneic hematopoietic stem cell transplantation"

Institution: Fred Hutchinson Cancer Research Center

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

Cancer Type: Leukemias, Lymphomas, Myeloma

Research Area: Basic Immunology

Christine M. Lovly, MD, PhD

Christine M. Lovly, MD, PhD

Lung cancer is responsible for more cancer-related deaths in the U.S. and worldwide each year than any other cancer. Historically, patients with advanced metastatic disease have been treated with conventional chemotherapy. Recently, however, subsets of lung cancer patients have been identified with specific molecular alterations that allow for treatment with rationally chosen targeted therapies. One molecular subset of lung cancer is characterized by the presence of alterations in a protein called ALK tyrosine kinase. Patients with lung cancers that harbor ALK fusions derive significant clinical benefit from a newly approved drug that blocks the action of the mutant ALK. Unfortunately, the degree and duration of tumor response to ALK inhibitor drugs varies, and patients inevitably develop progressive disease, or “acquired resistance.” Additional strategies are needed to improve the treatment of these lung cancer patients.
Dr. Lovly’s goal is to develop novel treatment strategies for ALK positive lung cancer. She plans to improve our understanding of how ALK fusions transmit signals to promote cancer and of how these signals become altered in the context of acquired resistance to ALK inhibitors. Her work will identify novel targets that can be blocked in combination with ALK inhibitors, to promote enhanced anti-tumor responses. Since ALK mutations have been described in a growing number of hematologic and solid organ tumors, an improved understanding of ALK signaling—as well as mechanisms of resistance to ALK inhibition—may also have potential implications for other cancers.




Project Title: "Developing novel therapeutic strategies for ALK-fusion positive lung cancer"

Institution: Vanderbilt University

Sponsor(s) / Mentor(s): William Pao, MD, PhD

Cancer Type: Lung

Research Area: Experimental Therapeutics

Deepak Nijhawan, MD, PhD

Deepak Nijhawan, MD, PhD

Despite recent advances, lung cancer remains the leading cause of cancer related death in the United States, and there is an urgent need for new therapies. The most successful treatments for lung cancer to date are the targeted drugs erlotinib and crizotinib. These drugs block tumor growth in cancers that respectively harbor either mutations in EGFR or translocations in the ALK gene. Unfortunately, only a minor fraction of patients’ tumors have EGFR mutations or ALK translocations; therefore, the vast majority of patients lack an effective targeted therapy.
Dr. Nijhawan aims to identify novel targets in lung cancer so that similarly effective therapy can be developed for other patients. He has identified a set of chemicals called benzothiazoles that are effective in blocking the growth of 25% of lung cancer cell types tested. The protein target of the benzothiazole and the genetic alterations that predict sensitivity are unknown.  His research focuses on identifying both the benzothiazole protein target as well as predictive biomarkers that explain why only certain lung cancers are susceptible to its effect.  The identification of these biomarkers in lung cancer patients may highlight a set of patients who could be treated with benzothiazole-related compounds.   




Project Title: "Using chemistry to identify new targets in lung cancer"

Institution: University of Texas Southwestern Medical Center

Sponsor(s) / Mentor(s): Steve L. McKnight, PhD, and David Johnson, MD

Cancer Type: Lung

Research Area: Chemical Biology

Ann Mullally, MD

Ann Mullally, MD

Myeloproliferative neoplasms (MPN) are a type of blood cancer sometimes considered to be “pre-leukemias” which can progress to leukemia and are also lethal cancers in their own right. A population of rare hematopoietic stem cells (HSC), called MPN disease-propagating cells, typically harbor mutations that cause the cells to overproliferate. These mutated HSC produce abnormal cancerous blood cells that over time can eliminate the normal blood cells in the bone marrow. In MPN, the cancerous blood cells secrete an excess of substances called growth factors that allow cancer cells to survive.

Dr. Mullally aims to understand which of the growth factors help the mutated HSC to survive and to then use drugs to block the activity of these growth factors, thus killing the mutated HSC. This approach will lead to more successful treatments for MPN and leukemia, resulting in a higher cure rate for patients.




Project Title: "Determining the role of aberrant growth factor signaling in maintaining disease-propagating cells and mediating JAK2 inhibitor resistance in myeloproliferative neoplasms"

Institution: Brigham and Women's Hospital

Sponsor(s) / Mentor(s): Benjamin L. Ebert, MD, and Daniel J. DeAngelo, MD

Cancer Type: Leukemias

Research Area: Stem Cell Biology

Himisha Beltran, MD

Himisha Beltran, MD

Many prostate cancers initially respond to treatments that block the hormone testosterone, thus halting tumor growth. These treatments block testosterone by targeting a molecule called the androgen receptor (AR). However, patients often develop resistance to these drugs, giving rise to an aggressive AR-independent form of prostate cancer. Often under-recognized, AR-negative neuroendocrine prostate cancer (NEPC) currently represents approximately 25% of advanced prostate cancers. The clinical diagnosis is most often made when the cancer has metastasized, especially to liver and brain, and is associated with a low prostate specific antigen (PSA) level. The poor prognosis of NEPC is, in part, due to an incomplete understanding of the molecular events underlying its development.
By utilizing valuable tissue resources and state-of-the-art technologies, Dr. Beltran [Damon Runyon-Gordon Family Clinical Investigator] seeks to comprehensively evaluate NEPC tumors for recurrent molecular alterations and determine their functional and clinical impact. She will identify a genomic profile that distinguishes NEPC from the more common type of prostate cancer, prostate adenocarcinoma, and evaluate the impact of NEPC-associated alterations on patient outcomes and their ability to predict patient response to available therapies. Her goal is to improve our understanding of molecular events associated with disease progression and help develop strategies toward preventing NEPC. Distinguishing NEPC will help identify prostate cancer patients unlikely to benefit from additional AR-targeted strategies and select patients for novel targeted treatment approaches for NEPC.




Project Title: "Utilizing genome sequencing to elucidate mechanisms of resistance in advanced prostate cancer"

Institution: Weill Medical College of Cornell University

Sponsor(s) / Mentor(s): Mark A. Rubin, MD

Cancer Type: Prostate

Research Area: Genomics

Lydia Finley, PhD

Lydia Finley, PhD

Dr. Finley [Jack Sorrell Fellow] examines how cells sense their nutritional status to regulate cell growth. Cancer cells rewire their metabolic pathways to support rapid growth, often subverting the normal checks and balances that guard against uncontrolled proliferation. Her research will provide insight into the metabolic cues that control growth in normal cells and the metabolic alterations that cancer cells may adopt to support tumorigenesis.




Project Title: "Regulation of cancer cell growth and survival by the propionate catabolic pathway"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Craig B. Thompson, MD

Cancer Type: All cancers, Colorectal

Research Area: Cell Biology

Nicholas Arpaia, PhD

Nicholas Arpaia, PhD

Dr. Arpaia [Robert Black Fellow] focuses on how the immune system distinguishes between beneficial gut bacteria versus those that may be pathogenic and cause disease. Changes in the levels of these microbes and the metabolites they produce are correlated with cancer-associated intestinal inflammatory disorders like Crohn's disease and ulcerative colitis. His research may aid in the development of new therapeutics aimed at treating aberrant inflammation that can lead to cancer.




Project Title: "The role of microbiota-derived metabolic signals in shaping the intestinal immune landscape "

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Alexander Y. Rudensky, PhD

Cancer Type: Colorectal

Research Area: Basic Immunology

Christine R. Beck, PhD

Christine R. Beck, PhD

Dr. Beck [HHMI Fellow]  is investigating the mechanisms that are involved in complex genomic rearrangements, such as gene duplications and triplications. The replication-based DNA repair pathways that lead to complexity and copy number gain in human genomes are not well understood. Studying the mechanisms by which copy number changes occur may elucidate fundamental processes that lead to cell transformation and cancer in humans.




Project Title: "Mechanisms underlying copy number gain in cancer and genomic disorderassociated complex rearrangements"

Institution: Baylor College of Medicine

Sponsor(s) / Mentor(s): James R. Lupski, MD, PhD

Cancer Type: All cancers

Research Area: Genomics

Chih-Yung Lee, PhD

Chih-Yung Lee, PhD

Dr. Lee [HHMI Fellow] is studying how the first germ cell is specified during embryonic development. Several characteristics of germ cells are reminiscent of cancer cells, including rapid proliferation, totipotency and immortality. Furthermore, proteins expressed specifically in the germline are often misexpressed in tumors. Identifying new genes and pathways required for germ cell development will provide insights into how re-activation of germ cell fate is triggered during tumorigenesis.




Project Title: "Regulation of primordial germ cell fate in C. elegans"

Institution: Johns Hopkins University

Sponsor(s) / Mentor(s): Geraldine Seydoux, PhD

Cancer Type: Testicular

Research Area: RNA

Gabriel C. Lander, PhD

Gabriel C. Lander, PhD

Dr. Lander will use high-resolution cryo-electron microscopy to characterize the structural organization of the large protein complexes that make up “molecular machines” in cells. By determining the molecular architecture of these machines, he aims to gain a more comprehensive understanding of the mechanisms that underlie important biological processes such as cell cycle regulation and cell division. He is currently focusing on a macromolecule called the proteasome, which recognizes and degrades unwanted or dangerous proteins. Recent studies suggest that the proteasome may play a role in suppressing tumorigenesis, and that certain antitumor drugs interact with the proteasome. This research will be invaluable in defining proteasomal biochemistry, potentially revealing novel approaches to detect and suppress the onset of tumorigenesis in a wide variety of cancers.




Project Title: "Deciphering the structural basis of macromolecular functions involved in cellular homeostasis"

Institution: The Scripps Research Institute

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Structural Biology

Ari J. Firestone, PhD

Ari J. Firestone, PhD

Dr. Firestone is exploring novel strategies for inhibiting the cancer-causing activity of the N-Ras oncoprotein, which plays an important role in promoting cellular growth and survival. Ras mutations frequently found in many types of cancer lead to uncontrolled proliferation. Using a combination of genetic and pharmacological approaches in mouse models of Ras-driven leukemia, he aims to determine whether disrupting the subcellular localization of Ras could be an effective therapeutic intervention.  




Project Title: "Investigation of Acyl Protein Thioesterase 1 and 2 as potential therapeutic targets in NRAS driven leukemias"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Kevin M. Shannon, MD

Cancer Type: Leukemias

Research Area: Signal Transduction

Maria M. Mihaylova, PhD

Maria M. Mihaylova, PhD

Dr. Mihaylova [Robert Black Fellow] aims to understand how aberrant nutrient sensing can lead to metabolic reprogramming and transformation. Utilizing a mouse model, she will examine the re-wiring of cellular metabolism in intestinal stem cells in response to dietary changes. She hopes that these studies will lead to insights about how nutrient sensing in these cells affects stem cell maintenance and tumorigenesis.




Project Title: "Examining how nutrient state dependent metabolic reprogramming in the Paneth cells controls intestinal stem cell renewal, differentiation and tumorigenesis"

Institution: Whitehead Institute for Biomedical Research

Sponsor(s) / Mentor(s): David M. Sabatini, MD, PhD

Cancer Type: All cancers, Gastric

Research Area: --

Wenyu Luo, PhD

Wenyu Luo, PhD

Dr. Luo is exploring the neuronal and genetic basis of stress-induced depression-like behavior in Drosophila. Loss of resilience to stress leads to depression and other mental disorders such as post-traumatic stress disorder, which may increase the risk of other severe diseases including liver and lung cancers. This research may develop new stress intervention approaches to improve quality of life in cancer patients.




Project Title: "A Drosophila model to study resilience to social stress and depression-like behavior"

Institution: University of California, San Francisco

Sponsor(s) / Mentor(s): Yuh-Nung Jan, PhD

Cancer Type: All cancers, Liver, Lung

Research Area: Animal Models/Mouse Models

Junjie U. Guo, PhD

Junjie U. Guo, PhD

Dr. Guo is investigating how regulatory RNAs function by interacting with their target RNAs. Misregulation of these interactions has been shown to contribute to tumorigenesis. He aims to develop a high-throughput experimental strategy that can identify these interactions within each RNA and between different RNAs. These findings will not only expand the current knowledge of existing types of RNA-RNA interactions, but will also reveal novel RNA-RNA interactions that may give rise to new therapeutic strategies.




Project Title: "Charting the in vivo landscape of RNA-RNA interactions"

Institution: Whitehead Institute for Biomedical Research

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

Cancer Type: All cancers

Research Area: RNA

Dmitriy Zamarin, MD, PhD

Dmitriy Zamarin, MD, PhD

Dr. Zamarin [Dr. Bart A. Kamen Fellow] is studying oncolytic viruses, a class of promising emerging cancer therapeutics. Oncolytic viruses can efficiently and specifically lyse cancer cells; they also induce important tumor-specific immune responses that can be active throughout the body. He is exploring different immunotherapeutic strategies to circumvent the limitations of oncolytic viruses and to make oncolytic virus-based immunotherapy applicable to all cancer types. 




Project Title: "Immunotherapeutic approach to cancer treatment integrating oncolytic virotherapy and immune checkpoint regulation"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s): Jedd D. Wolchok, MD, PhD

Cancer Type: All cancers

Research Area: Immunotherapy

Serkan Kir, PhD

Serkan Kir, PhD

Dr. Kir is studying the signaling mechanisms that mediate cancer cachexia, a wasting disorder of adipose fat tissue and skeletal muscle that leads to profound weight loss. Up to 50% of cancer patients suffer from cachexia, which reduces quality of life, limits treatment options and shortens survival time. Cancer cachexia increases the amount and activity of brown fat, a key metabolic tissue that dissipates chemical energy as heat. Identification of tumor-derived factors that regulate brown fat activity could lead to new therapeutic strategies to prevent cancer cachexia.




Project Title: "Identification of factors that induce brown fat activity in cancer cachexia"

Institution: Dana-Farber Cancer Institute

Sponsor(s) / Mentor(s): Bruce M. Spiegelman, PhD

Cancer Type: All cancers

Research Area: Cell Biology

Summer B. Thyme, PhD

Summer B. Thyme, PhD

Dr. Thyme [HHMI Fellow] is engineering protein tools to alter epigenetic modifications in important developmental pathways in a zebrafish model. Epigenetic misregulation, particularly of key regulators of cell fate specification, underlies a vast number of cancers. These tools could be applied to reprogram cell fate, as a means of treating epigenetically mediated diseases such as cancer.




Project Title: "Chromatin modifications and pioneer transcription factors in development"

Institution: Harvard University

Sponsor(s) / Mentor(s): Alexander F. Schier, PhD

Cancer Type: All cancers

Research Area: Epigenetics

Ozlem Yildirim, PhD

Ozlem Yildirim, PhD

Dr. Yildirim [HHMI Fellow] aims to identify factors that maintain cellular identity during mammalian cell proliferation. This will shed light on how cells remember which cell type they were and should become after division. A mechanistic understanding of this process will yield new insights into the many cell fate changes cancer cells display during their abnormal growth.




Project Title: "Role of LncRNAs in inheritance of chromatin states during self-renewal & differentiation"

Institution: Massachusetts General Hospital

Sponsor(s) / Mentor(s): Robert E. Kingston, PhD

Cancer Type: All cancers

Research Area: Chromatin Biology

Alba Diz Muñoz, PhD

Alba Diz Muñoz, PhD

Dr. Muñoz aims to develop a precise understanding of how cells migrate and decipher the differences between cell migration in a physiological context (such as immune cells) and that of a cancer cell. She will determine how physical forces affect specific molecular component(s) of the signaling pathway that directs motility. The ability to control cell migration would be a valuable tool for combating cancer metastasis.




Project Title: "How neutrophils convert changes in membrane tension to changes in intracellular signaling during chemotaxis"

Institution: University of California San Francisco, and University of California, Berkeley

Sponsor(s) / Mentor(s): Orion D. Weiner, PhD, and Daniel A. Fletcher, PhD

Cancer Type: All cancers

Research Area: Biophysics

Adam de la Zerda, PhD

Adam de la Zerda, PhD

Dr. de la Zerda is building tools that would allow scientists, for the first time, to look inside a tumor and directly visualize the signaling that takes place between cancer cells in a tumor.  Learning about this signaling is essential to our understanding of cancer growth, spread and response to treatment.  Such new understanding will ultimately translate to better diagnostic and therapeutic approaches.




Project Title: "Molecular imaging of cell-cell signaling in the tumor microenvironment"

Institution: Stanford University

Sponsor(s) / Mentor(s):

Cancer Type: Prostate

Research Area: Imaging

Evgenia N. Nikolova, PhD

Evgenia N. Nikolova, PhD

Dr. Nikolova [Robert Black Fellow] aims to elucidate the molecular mechanism of gene silencing mediated by the protein Kaiso. Kaiso interacts with its target DNA sequences to silence genes involved in the development and spread of cancer. Previous studies suggest that Kaiso acts as a tumor suppressor gene that can block cells from progressing to cancer; irregular Kaiso function is linked to cancer cell proliferation in a number of human cancers including colon, prostate, breast and lung cancers, as well as leukemia. Understanding the manner by which Kaiso associates with DNA and other proteins to control the expression of cancer-related genes may aid in the design of novel cancer treatments.




Project Title: "Recognition of methylated and specific DNA sequences by the zinc finger transcriptional repressor Kaiso and modulation by other nuclear factors"

Institution: The Scripps Research Institute

Sponsor(s) / Mentor(s): Peter E. Wright, PhD

Cancer Type: Breast, Gastric, Lung, Lymphomas, Prostate

Research Area: Biophysics

John J. Karijolich, PhD

John J. Karijolich, PhD

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), a cancer that commonly occurs in immunocompromised individuals, particularly in those infected by HIV. While several studies have suggested that HIV plays an important role in the development of KS, exactly how HIV/KSHV co-infection contributes to cancer formation is not well understood. Dr. Karijolich seeks to define mechanisms exploited by these two viruses to promote an environment conducive to cancer formation. The successful outcome of this work has the potential to identify novel mechanisms that promote the development of cancer, and may lead to novel therapeutic targets.




Project Title: "Characterizing mechanisms by which Kaposi sarcoma-associated herpesvirus modulates cellular gene expression"

Institution: University of California, Berkeley

Sponsor(s) / Mentor(s): Britt A. Glaunsinger, PhD

Cancer Type: All cancers

Research Area: Biochemistry

Bradley L. Pentelute, PhD

Bradley L. Pentelute, PhD

Antibodies have proven to be powerful tools in cancer research, facilitating the elucidation of disease mechanisms and generating novel and effective anti-cancer therapeutics. However, antibody biotechnology is limited by one major factor: the inability of antibodies to effectively cross the cell membrane to reach the inside of the cell, or cytosol. A new strategy is clearly necessary—one based on facile and reliable delivery of active antibody-like molecules into various cell types.

Dr. Pentelute plans to construct a new, targeted delivery platform capable of introducing stable molecules that mimic antibodies (deemed “intrabodies”). He will use this proposed delivery platform to strike the intracellular cancer target Bcr-Abl for treatment of chronic myeloid leukemia. He also aims to target the cancer-promoting complex p53/MDM2 in cancer cells. Through these innovative studies, he aims to advance the frontier by delivering a diverse array of antibody-like molecules into cells for cancer therapy.




Project Title: "Striking cancer with intracellular antibodies"

Institution: Massachusetts Institute of Technology

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Chemical Biology

Christine Mayr, MD, PhD

Christine Mayr, MD, PhD

[Island Outreach Foundation Innovator of the Damon Runyon-Rachleff Innovation Award]

Cancer is thought to arise through a series of genetic mutations in the DNA sequence. Depending on the location of these errors and the genes that are affected, these mutations lead to the many different features that characterize cancer cells such as uncontrolled proliferation, escape from cell death and metastasis.

Dr. Mayr proposes the existence of a new type of anomaly that can lead to cancer: non-genetic aberrations induced by modifications of RNAs, which have so far been excluded from large-scale cancer genomics efforts. She has developed a new method to identify this type of aberration in different cancers and will investigate its frequency and functional consequences for tumor growth. Her studies will help to broaden the understanding of cancers and may also help in the design of new therapeutics.




Project Title: "A functional atlas of lymphoma specific aberrations generated by RNA processing"

Institution: Memorial Sloan-Kettering Cancer Center

Sponsor(s) / Mentor(s):

Cancer Type: All cancers, Lymphomas

Research Area: Cancer Genetics

Agnel Sfeir, PhD

Agnel Sfeir, PhD

Each cell contains organelles called mitochondria, which are the powerhouses of cells, producing energy in the form of ATP. Mitochondria contain their own separate DNA, which codes for key energy-producing enzymes. Maintaining the integrity of the mitochondrial genome is necessary for optimal cellular function and for protection against diseases. Alterations in mitochondrial DNA are associated with and can promote metastasis of many tumors, such as lung, breast and prostate. Such aberrations range from single base substitutions to large-scale deletions that remove segments of the mitochondrial genome. The mechanism by which these aberrations influence disease progression remains unclear.

Dr. Sfeir aims to uncover the underlying basis for accumulation of these highly dangerous deletions in mitochondrial DNA and the mechanism by which they shape tumor behavior. This work will help identify novel strategies to preserve mitochondrial function and thwart tumor progression.




Project Title: "Pathways involved in preserving the genomic stability of mitochondrial DNA"

Institution: NYU Lagone Medical Center, Skirball Institute

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Cancer Genetics

Sarah (Sadie) M. Wignall, PhD

Sarah (Sadie) M. Wignall, PhD

[Lau/Palihapitiya Innovator]

Cancer cells exhibit uncontrolled growth and proliferation, leading to the formation of malignant tumors. Therefore, many current cancer therapies are aimed at trying to block cell multiplication, with the goal of killing cancerous cells and halting tumor growth. However, many of these treatments also affect the growth and division of non-cancerous cells in the body, leading to severe side effects. 

Dr. Wignall will investigate a pathway required for the division of cancerous, but not normal cells. This pathway regulates a physical structure in the cell called the centrosome. By learning more about this pathway, she hopes to ultimately contribute to designing therapies that will specifically attack cancer cells, leading to better treatment options for cancer patients.




Project Title: "Probing centrosome-clustering mechanisms to identify targets for new cancer therapies"

Institution: Northwestern University

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Proliferation/Cell Cycle

Nicholas E. Navin, PhD

Nicholas E. Navin, PhD

[Nadia's Gift Foundation Innovator]

Tumors evolve from single cells. As they expand to form the tumor mass, the cells diverge and form distinct subpopulations with different genetic mutations. This salient characteristic is called “intratumor heterogeneity” and confounds basic research and clinical diagnostics. The challenge is that standard genomic tools require a large amount of input material and thus are limited to measuring an average signal from a complex population of cells. 


Dr. Navin proposes the development of an innovative single-cell sequencing tool that can detect genomic mutations in single cancer cells, allowing heterogeneity in tumors to be delineated. He will apply this technique to study how single breast cancer cells disseminate from the primary tumor into the circulatory system and seed metastatic tumors. In addition, this method will have a myriad of clinical applications, which have prognostic value in predicting invasion, metastasis, survival and response to chemotherapy. Translating these methods into the clinic is likely to have a profound effect on reducing morbidity in breast cancer and other cancer types.




Project Title: "Developing single-cell sequencing methods to investigate metastatic seeding in breast cancer"

Institution: University of Texas MD Anderson Cancer Center

Sponsor(s) / Mentor(s):

Cancer Type: Breast

Research Area: Genomics

Trudy G. Oliver, PhD

Trudy G. Oliver, PhD

Many cancers initially respond to therapy. However, cancers often acquire resistance and stop responding to further treatment. Small cell lung cancer (SCLC) is an example of a cancer that is highly sensitive to initial treatment, but quickly acquires a vicious resistance resulting in a five-year patient survival rate of less than 4%. In order to combat drug resistance and improve the quality of life for patients with SCLC, it is important to understand the key genetic changes and cellular pathways that drive resistance.

Dr. Oliver will use the most innovative next-generation sequencing technologies to comprehensively identify critical genetic changes associated with resistance. These findings will be essential for understanding how lung cancer, and potentially other types of cancer, evades chemotherapy. In addition, this work will identify novel pathways that could be targeted to re-establish drug sensitivity and thereby provide new treatment options for patients with drug-resistant disease. 




Project Title: "Mechanisms of drug resistance in small cell lung cancer"

Institution: Huntsman Cancer Institute at the University of Utah

Sponsor(s) / Mentor(s):

Cancer Type: Lung

Research Area: Chemoresistance