All Cancers

Current Projects
David Q. Matus, PhD

Hallmarks of cancer progression are increases in both uncontrolled proliferation and invasive behavior, leading to the spread of tumor cells throughout the body. This collaborative project is founded upon an experimental observation made by Dr. Matus, in the model roundworm, C. elegans, that cell invasion and cell division are mutually exclusive behaviors. In other words, a cell cannot simultaneously invade and divide. This functional link between cell cycle arrest and invasive behavior has not been directly made before, although in a variety of cancers there is correlative data suggesting that tumor cells become less proliferative during invasion. Cell invasive behavior occurs during normal embryonic development, immune surveillance, and is dysregulated during metastatic cancer progression. As two cell and developmental biologists, Dr. Matus and Dr. Martin, will leverage their expertise in the strengths of two model systems, C. elegans and the zebrafish, D. rerio, to identify how regulation of the cell cycle intersects with acquisition of cell invasive behavior. Together, they will examine and manipulate the cell cycle state of human cancer cells during metastasis, visualizing invasive behavior at high resolution using light sheet microscopy. Insights from their work will have profound implications in future design of therapeutics to eradicate invasive cells that may escape traditional chemotherapeutic agents that only target actively dividing cells.

Project title: "Cell cycle regulation of cellular behaviors associated with cancer metastasis"
Institution: Stony Brook University
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Proliferation/Cell Cycle
Alesia N. McKeown, PhD

Dr. McKeown [HHMI Fellow] studies the innate immune system and its key role in suppressing many types of cancers. It is unclear why some cancers respond well to immunity-based therapies while others escape treatment and continue to spread. Her research is aimed at characterizing a new layer of host immunity composed of retrogenes of essential host proteins. She believes that these retrogenes act to inhibit viral infection by acting as nonfunctional “decoys” of host proteins required for the viral life cycle. By investigating how these decoys exert their antiviral function, she hopes to better understand the landscape of host immunity and utilize these new genes as potential therapeutics to halt similar pathways involved in cancer progression.

Project title: "Novel roles for retrogenes in host immunity"
Institution: University of Utah School of Medicine
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Nels Elde, PhD, and Cedric Feschotte, PhD
Cancer Type: All Cancers
Research Area: Evolution
Kara L. McKinley, PhD

Dr. McKinley studies how cells change their shape and behavior to build the complex structures that comprise mammalian organs. Cellular behaviors that occur during embryonic development are frequently co-opted by cancer cells during tumorigenesis and metastasis. Her goal is to understand how the machinery within cells drives changes in tissue architecture in a developmental context, generating new insights into how these cellular processes are corrupted during cancer progression.

Project title: "Mechanisms and functions of cellular rearrangements in epithelia"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Ronald D. Vale, PhD
Cancer Type: All Cancers
Research Area: Cell Biology
Wayne O. Miles, PhD

Inactivation of the Retinoblastoma 1 (RB) tumor-suppressor gene is a hallmark of cancer. Loss of RB function results in the transcription of genes required for cell growth but surprisingly also cell death. Profiling of RB-deficient cells showed that these cell death mRNAs are induced but not made into protein. Dr. Miles aims to identify the factors that block the production of cell death proteins and determine which of these factors prevent RB-lacking cancer cells from dying. As the RB pathway is disabled in almost all tumors, his research will provide insights into the mechanisms supporting cancer cell survival and as well as those preventing the death of cancer cells.

Project title: "Maximizing pro-apoptotic protein levels"
Institution: The Ohio State University
Award Program: Innovator
Cancer Type: All Cancers
Research Area: RNA (RNA processing, miRNA and piRNA mechanisms, enzymatic RNAs, etc.)
Matthew P. Miller, PhD

Dr. Miller 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. The vast majority of solid tumors have incorrectly positioned chromosomes, causing high levels of genomic instability and DNA damage. Very little is known about how chromosome segregation becomes so defective during tumorigenesis. His research is focused on elucidating the mechanisms of both accurate and defective chromosome segregation with the goal of determining whether there are opportunities for development of new cancer therapeutics.

Project title: "Regulation of kinetochore assembly"
Institution: Fred Hutchinson Cancer Research Center
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Cell Biology
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. 

Project title: "Characterization of novel pathogenic pathways in cancer: do tumor cells use quorum-sensing molecules to support malignancy?"
Institution: The University of Chicago
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Research Area: Chemical Biology
Andrew C. Murley, PhD

Dr. Murley is studying how the rapid growth of cancer cells exerts damaging stress on their subcellular compartments. In many cells, chronic stress of one of these compartments, called the endoplasmic reticulum, leads to cell death, but many types of cancer cells are able to avoid this fate. Recent findings point to the existence of secreted molecules released by cells when they are subjected to this stress. These molecules, whose identities are still unknown, can activate processes in neighboring cells, or in the secreting cells themselves, which protect them from this chronic stress. His goal is to identify these molecules and explore their role in cancer cell survival and other normal bodily functions. 

Project title: "Cell non-autonomous communication of ER stress resistance"
Institution: University of California, Berkeley
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Andrew G. Dillin, PhD
Cancer Type: All Cancers
Research Area: Aging
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
Named Award: Connie and Bob Lurie Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): James A. Wells, PhD
Cancer Type: All Cancers
Research Area: Chemical Biology
Vu Quang Nguyen, PhD

Dr. Nguyen uses advanced fluorescence microscopy to visualize how defined structural changes in chromatin, the condensed form of DNA, affect its association with factors required for transcription initiation-an early and essential step in gene expression. Architectural defects in chromatin are found in many cancers and have been linked to aberrant patterns of gene expression. The results of this research will be important in characterizing the connection between chromatin organization and cancer-associated gene misregulation.

Project title: "Role of chromatin organization in dynamics of transcription initiation"
Institution: Johns Hopkins University
Award Program: Fellow
Sponsor(s) / Mentor(s): Carl Wu, PhD
Cancer Type: All Cancers
Research Area: Chromatin Biology
Thomas M. Norman, PhD

Dr. Norman 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
Award Program: Fellow
Sponsor(s) / Mentor(s): Jonathan S. Weissman, PhD
Cancer Type: All Cancers
Research Area: Systems Biology
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