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Matthew R. Clay, PhD

Matthew R. Clay, PhD

Dr. Clay [HHMI Fellow] is investigating how cells in their natural environment move across basement membranes–the extracellular matrix of proteins that surrounds tissues. Basement membrane “breaching” is the first step of cell invasion, which underlies cancer metastasis. He aims to understand how signals from outside the cell are coordinated with, and integrated into, pathways within the cell that initiate basement membrane breach and cell invasion. These studies will uncover fundamental mechanisms that govern cell invasion and drive the deadly progression of cancers.




Project Title: "Understanding how extrinsic signals direct a Rho GTPase switch to control cell invasion in vivo"

Institution: Duke University

Sponsor(s) / Mentor(s): David R. Sherwood, PhD

Cancer Type: All cancers

Research Area: Invasion and Metastasis

Sigrid Nachtergaele, PhD

Sigrid Nachtergaele, PhD

Dr. Nachtergaele is investigating the roles of a chemical modification of mRNA called methylation. Many enzymes that add and remove RNA modifications impact developmental processes and cancer proliferation, but how they are regulated remains a mystery. She aims to identify the mechanisms by which mRNA methylation alters gene expression and eventually results in altered cell signaling and growth. Her goals are to understand these regulatory principles, to uncover how they become misregulated in disease, and to exploit these processes to identify novel cancer therapeutic targets.




Project Title: "Regulation of METTL3-METTL14-mediated N6-methyladenosine modification of mRNA"

Institution: The University of Chicago

Sponsor(s) / Mentor(s): Chuan He, PhD

Cancer Type: Breast, Leukemias, Lung

Research Area: Chemical Biology

William Razzell, PhD

William Razzell, PhD

Dr. Razzell [HHMI Fellow] is using cell biological, molecular genetic, and biophysical approaches to understand how cell-derived mechanical forces contribute to tumorigenesis through the modulation of cellular signaling pathways. One pathway that is responsive to mechanical forces is the Hippo pathway, which prevents excessive tissue growth during development. Characterizing how cell-derived forces control normal Hippo signaling will provide insight into the mechanisms by which Hippo pathway misregulation contributes to tumor progression.




Project Title: "The role of tension in Hippo pathway signaling"

Institution: Memorial Sloan-Kettering Cancer Center

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

Cancer Type: All cancers, Leukemias

Research Area: Developmental Biology

Rand M. Miller, PhD

Rand M. Miller, PhD

Dr. Miller is interested in understanding the mechanisms by which cancers become resistant to chemotherapeutic agents. Many cancers acquire resistance to drugs by overproducing molecular “pumps” called multidrug resistance (MDR) proteins, which actively export the toxic drug molecules out of cells. Using a variety of chemical techniques, he will investigate how these pumps mediate drug resistance in cancers, as well as their roles in the maintenance of healthy cellular function. Ultimately, this work may facilitate the design of better compounds targeting MDR pumps to overcome drug resistance.





Project Title: "Chemistry-based dissection of multidrug resistance efflux pump mechanisms in living cells"

Institution: The Rockefeller University

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

Cancer Type:

Research Area: Chemical Biology

Aaron D. Viny, MD

Aaron D. Viny, MD

Dr. Viny is studying the oncogenic role of abnormalities in the cohesin complex-a group of proteins that function to align and stabilize sister chromatids (copies of the chromosomes) during cell division. Mutations within several proteins in this complex have been identified in solid tumors and hematologic malignancies, particularly acute myeloid leukemia, the most common adult leukemia. Although it was presumed these mutations would result in unbalanced chromosomal breaks, this outcome has not yet been observed. He is exploring the mechanistic role of cohesin mutations in cancer pathophysiology and is investigating novel targeted therapies to block this pathway.




Project Title: "Role of the cohesin complex in oncogenic transformation of AML"

Institution: Memorial Sloan-Kettering Cancer Center

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

Cancer Type: Leukemias

Research Area: Cancer Genetics

David W. Taylor, PhD

David W. Taylor, PhD

Dr. Taylor is studying the structural biology of bacterial CRISPR-Cas surveillance complexes, which have been adopted as versatile genome engineering tools. He aims to decipher the principles by which these complexes function and to apply them for cancer research and therapeutics.




Project Title: "Structures of the RNA-targeting CRISPR-Cas complex Cmr"

Institution: University of California, Berkeley

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

Cancer Type: All cancers

Research Area: Structural Biology

Michael J. Smanski, PhD

Michael J. Smanski, PhD

Dr. Smanski is examining magnetic nanoparticles (MNPs), which possess unique physical properties that have led to several clinical applications in cancer diagnosis and therapy. Several species of bacteria have been found to naturally produce MNPs with exquisite control over size and shape that is unmatched by current chemical synthesis methods. He aims to understand how bacterial synthesis of MNPs relies on the coordinated expression of several dozen genes.




Project Title: "Establishing a versatile platform for functionalizing biological magnetic nano-particles "

Institution: University of Minnesota

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

Cancer Type: All cancers

Research Area: Systems Biology

Arun P. Wiita, MD, PhD

Arun P. Wiita, MD, PhD

Dr. Wiita is using a powerful technique called mass spectrometry to isolate and identify proteins degraded during cell death and released into the bloodstream shortly after starting chemotherapy.  Chemotherapy is frequently the mainstay of therapy for patients with cancer, yet the current tests available to assess whether chemotherapy is working are typically quite expensive and can only be used weeks to months after the start of therapy. His goal is to identify proteins that can serve as rapid and inexpensive markers of chemotherapeutic efficacy, enabling more effective individualized chemotherapeutic regimens for cancer patients.

 




Project Title: "Novel biomarker discovery for monitoring chemotherapeutic efficacy"

Institution: University of California, San Francisco

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

Cancer Type: Leukemias, Lymphomas, Myeloma

Research Area: Diagnostics

Brian H. Shirts, MD, PhD

Brian H. Shirts, MD, PhD

Clinical testing for inherited cancer risk often leads to identification of rare genetic variants, but it is uncertain if these variants affect cancer risk. This uncertainty is difficult for cancer patients who want to know the best way to prevent future cancers in themselves and their families.

Dr. Shirts is a clinical geneticist whose goal is to empower patients who have been diagnosed with rare genetic mutations (variants of uncertain significance, or VUS) to actively participate in family tree pedigree building to understand their own genetic risk for cancer and other diseases. He will develop an online toolkit to help cancer patients use publicly available genealogy and networking resources to determine if their own variants travel with cancer in their extended family. This project will pioneer an efficient way for patients and their families to work with genetics laboratories to classify VUS, giving cancer patients control over their own genetic information. This innovative strategy will also create a new source for the highest quality genotype-cancer correlation data, which will benefit cancer researchers and, eventually, everyone at risk for cancer.




Project Title: "Participatory genetics for defining genotype-phenotupe associations of rare cancer variants"

Institution: University of Washington

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

Cancer Type: All cancers

Research Area: Cancer Genetics

Nicholas T. Ingolia, PhD

Nicholas T. Ingolia, PhD

The uncontrolled growth and metastasis of cancer cells is driven by changes in the genes expressed by these cells, relative to cells in healthy tissue. Understanding these gene expression changes provides key insights into the behaviors of cancer cells and guides the design of anti-cancer therapies.
Dr. Ingolia is studying a cellular process called translation, which generates protein from RNA. Important gene expression changes result from differences in the translation of mRNAs into functional proteins, rather than the abundance of these mRNAs in the cell. He has developed innovative techniques to comprehensively profile translation in cells and proposes to apply this approach to understand the gene expression differences between normal and cancerous cells. These gene expression changes will reveal distinctive features of cancer cells that explain their pathological behavior and potentially expose new vulnerabilities of these cells that could be targeted to treat cancer.




Project Title: "Cis-regulatory code for the translational control of gene expression"

Institution: University of California, Berkeley

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

Cancer Type: All cancers

Research Area: Genomics

Elçin Ünal, PhD

Elçin Ünal, PhD

Aging is the primary risk factor for developing cancer. Despite the growing list of age-associated defects, we do not yet understand why aging is one of the most potent carcinogens.

Dr. Ünal proposes to study a natural developmental process, called gametogenesis, which reverses cellular aging. She will use this as a platform to illuminate the molecular causes of aging and to develop new strategies to counteract age-induced cellular damage. Her approach will identify the genes that play a direct role in attenuating the aging process and could facilitate the development of novel strategies to improve human health by decreasing susceptibility to cancer.




Project Title: "Reducing cancer susceptability by attenuating cellular aging"

Institution: University of California, Berkeley

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

Cancer Type: All cancers

Research Area: Aging

Chris M. Jewell, PhD

Chris M. Jewell, PhD

Tumors evade the immune system by suppressing the function of T cells otherwise capable of destroying cancer cells. These T cells develop in lymph nodes - specialized tissues that control responses against cancer, infection, and other disease. As T cells become activated against tumors, the cells differentiate and proliferate at much slower rates. This decreased proliferation dramatically reduces the effectiveness of anti-tumor immune responses.
Dr. Jewell is uniquely trained in both immunology and materials science. He is harnessing bioengineering, immunology, and polymer design to create degradable vaccine "depots" in lymph nodes. The goal is to use these depots to control how T cells develop, promoting a cell fate specific for attacking tumors that also maintains the ability to proliferate at the extremely high rates needed to clear existing tumors and protect against regrowth. This is the first time these ideas have been explored, and the findings from his research will support development of a new class of cancer vaccines that could clear existing tumors and prevent relapse.




Project Title: "Harnessing intra-lymph node controlled release to study and enhance tumor immunity"

Institution: University of Maryland

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

Cancer Type: All cancers

Research Area: Biomedical Engineering

Ning Jiang, PhD

Ning Jiang, PhD

Many diseases could be cured if the power of our own immune systems could be harnessed. For cancer, the theory of "cancer immunoediting" provides a hypothesis for how tumors escape detection by the immune system.

Dr. Jiang, a biomedical engineer, works at the interface of systems biology, genomics, and immunology. Her lab is developing a single cell-based integrated technological approach to challenge this theory. She will profile the immune system repertoire for antigen specificity, receptor gene sequences, and cellular function-related gene expression. Her approach may provide explanations for why and how the immune system tolerates tumors. Her proposed study may result in a paradigm shift that could improve cancer immunotherapies and also revolutionize health care with new personalized immune metrics for early disease detection and targeted therapy.




Project Title: "A single cell integrated system to dissecting cancer immunoediting in humans"

Institution: University of Texas, Austin

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

Cancer Type: All cancers

Research Area: Tumor Immunology

Guillem Pratx, PhD

Guillem Pratx, PhD

Many studies have shown that the cancer cells within a tumor form a remarkably diverse population. These cellular differences play a significant role in how the tumor develops and how it responds to therapy. A technology called flow cytometry (a high-throughput method for characterizing single cells) has been critical for these findings; however, the technology is inherently limited because it can only measure biochemical processes that can be interrogated using a fluorescent molecule.
Dr. Pratx, an engineer by training, is developing a novel method that would enable flow cytometry to measure single cell uptake of any non-fluorescent molecule. This challenging feat will be accomplished by exploiting the fact that molecules can be labeled by radioisotopes. This new tool could transform the ability to study normal and abnormal molecular processes in single cancer cells by allowing flow cytometry to interrogate a much wider range of biomolecules, with high throughput and high temporal resolution.




Project Title: "Adding a new dimension to flow cytometry: radionuclide-activated cell sorting"

Institution: Stanford University

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

Cancer Type: All cancers

Research Area: Biomedical Engineering

Thomas M. Norman, PhD

Thomas M. Norman, PhD

Thomas Norman, PhD, with his sponsor Jonathan Weissman, PhD, at the University of California, San Francisco, is investigating the role that "epigenetic" differences play in cancer cells' ability to develop drug resistance. These epigenetic changes result in altered gene expression. He will use a new technique called CRISPRi to systematically tune the expression of different parts of the genome and measure their effect on drug resistance. He hopes that these studies will identify new avenues for reducing resistance and expand our knowledge of the role epigenetic factors play in leukemia and other cancers.




Project Title: "Identifying the stochastic determinants of drug resistance"

Institution: University of California, San Francisco

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

Cancer Type: All cancers

Research Area: Systems Biology

Jonathan R. Whicher, PhD

Jonathan R. Whicher, PhD

Dr. Whicher focuses on a cellular structure called the voltage-gated potassium channel Eag1, which can promote tumor growth and is aberrantly expressed in many types of cancer including breast, colon, prostate, lung, and liver. He is determining the structure and mechanism of Eag1 in order to elucidate how Eag1 promotes cancer growth, with the eventual goal of developing Eag1 modulators as potential anti-cancer therapies.




Project Title: "Structure and mechanism of the voltage-gated potassium channel hEag1"

Institution: The Rockefeller University

Sponsor(s) / Mentor(s): Roderick MacKinnon, MD

Cancer Type: All cancers

Research Area: Structural Biology

Albert Tsai, PhD

Albert Tsai, PhD

Dr. Tsai is studying a process called translation, by which messenger RNAs (mRNAs) are decoded into proteins. A hallmark of cancer cells is distorted patterns of protein production, leading to uncontrolled growth and invasive behavior. He is using novel microscope technology to image live cells in real-time and developing techniques to image individual protein molecules during their synthesis, thereby linking the time, location and amount of protein production to individual mRNAs. He will first examine these processes in bone cancer-derived cell lines. He will also examine how neurons control translation of structural proteins in the precise location where the neuron is stimulated, which underlies memory formation and learning. Ultimately, this work will contribute toward a precise and predictive model for translational control that explains how cancer cells circumvent control mechanisms.




Project Title: "In vivo imaging of translation dynamics on an mRNA."

Institution: HHMI Janelia Farm Research Campus

Sponsor(s) / Mentor(s): Robert H. Singer, PhD

Cancer Type: All cancers

Research Area: Biophysics

Kai Mao, PhD

Kai Mao, PhD

Dr. Mao is studying the cell's cytoskeleton, which provides the physical structure and shape of a cell. The cytoskeleton is an attractive target for cancer chemotherapy because of its central function in mitosis or cell division, but these chemotherapeutic agents have very high toxicity. He hypothesizes that the next generation of chemotherapy will benefit from the inhibition of these toxin response pathways. He will examine how cells respond to such drugs, with the goal of applying these findings to attenuate the drugs' side effects.




Project Title: "Mechanisms of xenobiotic surveillance and regulation"

Institution: Massachusetts General Hospital

Sponsor(s) / Mentor(s): Gary Ruvkun, PhD

Cancer Type: All cancers

Research Area: Toxicology/Toxicogenomics

Anupam K. Chakravarty, PhD

Anupam K. Chakravarty, PhD

Dr. Chakravarty [HHMI Fellow] is investigating heritable physical structures, called higher order assemblies, formed upon overexpression of RNA binding proteins. RNA binding proteins are consistently overexpressed in multiple cancers. His research will illuminate the mechanism of assembly formation and its role in altering gene regulation, thereby suggesting novel avenues to potential therapeutic intervention.




Project Title: "Investigating the phenomenon of epigenetic inheritance mediated by non-amyloid protein aggregates"

Institution: Stanford University School of Medicine

Sponsor(s) / Mentor(s): Daniel F. Jarosz, PhD

Cancer Type: All cancers, Leukemias

Research Area: Epigenetics

Magdalena E. Potok, PhD

Magdalena E. Potok, PhD

Dr. Potok [HHMI Fellow] is investigating how gene expression is controlled by heterochromatin (the physically compacted form of DNA) and genomic instability. In the plant Arabidopsis thaliana, reduction in a chemical mark on the chromatin, called H3K27me1, results in heterochromatin decompaction, abnormal gene expression and the production of extra DNA from certain regions. Extra copies of DNA are a sign of genomic instability often observed in cancers. She will characterize the mechanism underlying genomic instability. The results of this study may add insight into the connection between epigenetic gene silencing, nuclear architecture, and genome stability, leading to an understanding of why they are misregulated in cancer.




Project Title: "The relationship between epigenetic gene silencing, nuclear architecture, and genome stability."

Institution: University of California, Los Angeles

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

Cancer Type: All cancers

Research Area: Epigenetics

Andrew L. Wolfe, PhD

Andrew L. Wolfe, PhD

Dr. Wolfe studies PTEN, an anti-cancer protein that opposes cell growth and can induce cancer cells to die. Loss of PTEN protein has been detected in nearly every form of cancer and is associated with drug resistance and poor clinical outcome. A new, longer form of PTEN, called PTEN-L, was recently discovered. Unlike PTEN, PTEN-L can penetrate cancer cells from the outside to instruct them to die, giving this protein great potential as a novel naturally occurring cancer therapy: the cell-penetrating tumor suppressor protein. He aims to answer fundamental questions about the mechanism and function of PTEN-L, which will characterize the expression and regulation of this important anti-cancer protein for the first time. In addition, this work will directly test tumor suppressor proteins as exciting new drugs with potentially broad therapeutic applications against many forms of cancer.




Project Title: "PTEN-L: Physiological function, regulation, and therapeutic possibilities"

Institution: Icahn School of Medicine at Mount Sinai

Sponsor(s) / Mentor(s): Ramon Parsons, MD, PhD

Cancer Type: All cancers

Research Area: Cancer Genetics

Jeanine L. Van Nostrand, PhD

Jeanine L. Van Nostrand, PhD

Dr. Van Nostrand aims to understand how signaling pathways involved in the energetic and metabolic stress responses prevent cancer. She will generate mouse models harboring specific mutations that prevent the stress response, and evaluate the effects of these mutations on lung cancer development. Furthermore, using exercise and caloric restriction, she will elicit the metabolic stress response in these animals to understand how energetic stresses prevent cancer development and progression. This work will both expand knowledge of how cells respond to energy stress and metabolic changes to suppress tumorigenesis and aid in establishing effective preventative and therapeutic strategies for cancer patients.




Project Title: "Elucidating the AMPK-dependent regulation of mTOR signaling in the metabolic checkpoint of tumorigenesis."

Institution: Salk Institute

Sponsor(s) / Mentor(s): Reuben J. Shaw, PhD

Cancer Type: Lung

Research Area: Animal Models/Mouse Models

Ronald J. Hause, PhD

Ronald J. Hause, PhD

Dr. Hause is developing new experimental and analytical methods to better understand, interpret and predict how genetic mutations affect individuals' risks for cancers and responses to chemotherapy. He will use a combination of genomic, biochemical, and machine learning approaches to investigate and model the effects of all possible mutations of a gene involved in chemotherapeutic drug response and relate these results to patient outcome. This research will establish a new paradigm for examining the effects of mutations in clinically relevant genes and help physicians better interpret mutations when treating cancer patients to maximize effectiveness while minimizing harmful side effects.




Project Title: "Function dissection of the effects of variants of uncertain significance in TPMT in response to thiopurine anticancer agents."

Institution: University of Washington

Sponsor(s) / Mentor(s): Jay A. Shendure, MD, PhD

Cancer Type: All cancers

Research Area: Pharmacogenomics and Biomarkers

Cole Trapnell, PhD

Cole Trapnell, PhD

Dr. Trapnell studies the vast complexity underlying cell identity and fate. He will use genomic and computational biology approaches to analyze individual tumor cells and examine how a variety of genetic mutations give rise to aggressive tumor cell behavior. He aims to map the key pathways controlling cell fate, ultimately leading to information that may aid the development of more effective targeted therapies.




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

Institution: University of Washington

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Cell Biology

Caitlin A. Brennan, PhD

Caitlin A. Brennan, PhD

Dr. Brennan [Dennis and Marsha Dammerman Fellow] studies colorectal cancer and its connection to the human microbiota- the collection of bacteria and other microbes found associated with the body in both healthy and disease states. One such organism is Fusobacterium nucleatum, a bacterium that is naturally found in the mouths and gastrointestinal tract of healthy individuals. This bacterium is also observed in high abundance in some colorectal tumors relative to healthy colon tissue within the same person; experimental studies have demonstrated that this bacterium actively promotes tumor development. Her research will investigate how Fusobacterium signals to both the immune system and other microbes in the developing tumor environment, offering insight into the potential utility of Fusobacterium as a diagnostic or therapeutic target for colorectal cancer.




Project Title: "Mechanisms underlying Fusobacterium nucleatum-driven colorectal cancer"

Institution: Harvard School of Public Health

Sponsor(s) / Mentor(s): Wendy S. Garrett, MD, PhD

Cancer Type: Colorectal

Research Area: Microbiology

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 T. Oh, MD, PhD

Stephen T. 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 S. Hammerman, MD, PhD

Peter S. 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 [Philip O'Bryan Montgomery, Jr., MD, Fellow] 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

David K. Breslow, PhD

David K. Breslow, PhD

Dr. Breslow is studying the primary cilium, a cellular structure that enables cells to sense and respond to specific external cues. While disruptions to primary cilia are known to promote tumor formation and cause developmental defects, how cilia orchestrate these processes remains poorly understood. He is using a combination of genomic, biochemical and cell biology approaches to investigate how specific signaling occurs in the cilia.




Project Title: ""Dissecting the role of the ciliary transport machinery in oncogenic signal transduction""

Institution: Stanford University

Sponsor(s) / Mentor(s):

Cancer Type: All cancers

Research Area: Cell Biology

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

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: "Identification of cysteine liabilities in NRF2-driven cancers."

Institution: The Scripps Research Institute

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

Cancer Type: All cancers

Research Area: Chemical Biology

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

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