Dr. Liu studies cachexia, a complex metabolic syndrome characterized by a rapid and irreversible loss of body mass, which significantly impedes disease treatment success. This body-wasting phenomenon is a common feature in many types of cancers, but the causes are unknown. She is investigating the tumor-derived signaling mechanisms that lead to systemic cachexia and muscle wasting. As no current therapies exist for the reversal or delay of cachexic symptoms, identifying the triggers that lead to systemic body mass loss is imperative to improve our understanding of all cancers and to identify putative drug targets.

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.

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.

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.

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.

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.

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.

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.

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. 

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.