Damon Runyon News

Dr. King (Berger Foundation Fellow) is studying mechanisms by which nutrient-deprived cancer cells utilize extracellular proteins as a source of amino acids to promote their growth and survival. The bulk uptake of extracellular material, through a process called macropinocytosis, is a major means of nutrient uptake in single-celled, amoeboid organisms. Recent evidence suggests that mutations prevalent in cancer cells can activate this ancient scavenging mechanism.

Dr. Tian 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.

Dr. Barton investigates the regulation of cell migration. Specifically, she aims to understand how spatial information is generated to guide migrating cells and how cell migration is terminated when the target tissue is reached. To gain insights into these processes, she is studying migration of Drosophila germ cells to the gonad during embryogenesis as a model system. Because many features of Drosophila germ cell migration are similar to tumor cell migration, novel processes discovered with this model system will shed light on the mechanisms of metastasis.

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.

Dr. Umbreit [HHMI Fellow] studies chromosome segregation, the process by which the genetic information on chromosomes is duplicated and the copies are segregated equally into two new cells. Cancer cell proliferation is marked by frequent errors in chromosome segregation, resulting in abnormal genetic content in the progeny. He is investigating one type of chromosome segregation error, called a “chromosome bridge,” a major mechanism through which genetic information can be amplified and/or rearranged to distort gene function in cancer cells.

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.

Dr. Murrow is using an engineered 3D model of the human mammary gland to determine how stem cells in the breast sense and respond to overall cellular composition. She aims to understand how sparsely distributed stem cells use local cues in the tissue to sense global changes in cell number. Since loss of tissue organization and abnormal stem cell differentiation are two key features underlying breast cancer development, this work will help identify new strategies for breast cancer prevention and treatment.

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.

Dr. Baldridge 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.

Dr. Caldas is investigating the mechanisms by which RNA interference (RNAi) related pathways, implicated in cancer primarily through their role in regulating gene expression, contribute to the fidelity of cell division. In addition to major changes in gene expression, a hallmark of many cancers is genome instability and chromosome loss, processes highly related to inaccurate cell division. Using C. elegans as a model system, her goal is to identify new aspects of cell division control that can be targeted for cancer therapy.