Damon Runyon News

Dr. Nachtergaele [HHMI Fellow] 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.

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.

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.

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.

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.

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.

Dr. Razzell 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. He will focus on one pathway that is responsive to mechanical forces, the Hippo pathway, which prevents excessive tissue growth during development.

Dr. Russell [Merck Fellow] is investigating the mechanisms by which cells recognize influenza infection. Yearly influenza epidemics present an ongoing medical challenge, and those suffering from cancer are at a potentially increased risk of complication following infection. By identifying both cell-to-cell differences in the response to viral infection and virus-to-virus differences in the capacity to evade the host response, he hopes to develop a better understanding of the kinetics of initial infection and disease progression in individuals.

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.

Dr. Levin [HHMI Fellow] studies how resident microorganisms can manipulate the development of their animal hosts. Through novel genetic approaches, she will explore the mechanisms used by the bacterium Legionella to dramatically disrupt the cell divisions of its host, amoeba. Because cancerous growth is often driven by the dysregulation of developmental signaling pathways, understanding the mechanistic impacts of resident microbes promises to illuminate both normal and cancer development.