The Cancer Cell Biology Branch [CCBB] supports and directs a comprehensive research program that defines the biological basis for the differences between normal cells and cancer cells, with a major emphasis on studies that reveal processes and molecular targets where there is potential for therapeutic or preventive intervention. Of high priority in the CCBB's portfolio are studies to reveal the basic mechanisms that drive the development and behavior of cancer cells, discover how events associated with transformation disrupt the normal biological programs of cell proliferation and death, and examine the functional effects of genetic alterations that underlie tumorigenesis. Characteristic features of the cancer cell phenotype include, but are not limited to, expanded replicative potential, resistance to metabolic and oxidative stress, ability to evade programmed cell death, reduced dependence on growth factor signals, insensitivity to growth inhibitory signals, genomic plasticity and resistance to chemotherapeutic intervention. Studies of normal biology are also supported if the goal is to elucidate dysregulated processes critical for the progression of normal cells to cancer cells. Various in vivo and in vitro systems are utilized including tumor-bearing animals, human and animal tumor tissues and cells, non-mammalian organisms and biochemical approaches.
Cancer Cell Physiology: Cancer Cell Metabolism (Ming Lei)
Altered cellular metabolism, including metabolism of endogenous factors, mechanisms of regulating metabolic fuel homeostasis, and insulin regulatory processes, for example, the Warburg Effect, the balance between glycolysis and oxidative phosphorylation, the switch to cachexia at the cellular level, the link between protein translation or ribosome biogenesis and cellular metabolism, alternations in nucleic acid and fatty acid metabolism, integration of sugar, nucleic acid and fatty acid metabolites, tumor metabolite profiling and characterization; biologic effects of reactive oxygen species (ROS) generated by aberrant metabolism on tumorigenesis; and Studies of autophagy relevant to nutrient stress and recycling of damaged organelle and protein components; dysregulated organelle biogenesis and function (e.g., mitochondria, endoplasmic reticulum, Golgi, vesicles) in the cancer cell;
Cancer Cell Physiology: Response to Stress (Konstantin Salnikow)
Responses to cellular stress, for example, oxidative stress, unfolded protein response (UPR), ER stress, hypoxia, and inflammation, that influence cancer cell physiology and tumor growth; characterization of autophagy including how it regulates the balance between cell survival and death, protects cancer cells from various stressors; Early molecular events that lead to oncogenic transformation including cellular stress that leads to epigenetic changes and genomic instability; Cell death, including but not limited to, apoptosis, necrosis, autophagic cell death, anoikis and other forms of programmed or non-programmed cell death that when dysregulated lead to enhanced cell survival or resistance to cancer therapy; Processing and trafficking of intracellular membranes and proteins, protein maturation, endosome sorting and recycling, nuclear and cytoplasmic transport in the context of the cancer phenotype; and Intracellular signaling and processing of growth factors, cytokines and their associated receptors in the context of cancer cell growth and gene regulation;
Cancer Cell Growth and Cell Cycle Control (Barbara Spalholz)
Altered cell cycle regulation and checkpoints that may contribute to oncogenic transformation, including characterization of factors that regulate the cell cycle, mitosis, cytokinesis, centrosome duplication, and DNA replication; The role of genes and proteins controlling circadian rhythm in cancer cell biology; and Proteasome induced degradation and associated mechanisms that lead to alterations in protein stability and function in relationship to oncogenic transformation, including protein modifications by ubiquitylation, sumoylation, or other mechanisms;
Post-transcriptional gene regulation and cancer (Jennifer Strasburger)
Post-transcriptional gene expression regulation influencing the cancer phenotype, including RNA stability, splicing, transport, and translation and the role of microRNAs in the regulation of splicing, translation or mRNA stability; and Alterations in protein function influencing the cancer cell phenotype due to changes in protein maturation, post-translational modifications, sorting, and abnormal degradation. Academic Research Enhancement Awards (AREA R15) and Conference Grants (R13)
Cellular Transformation: Oncogenes and Tumor Suppressors (Vacant)
Oncogene and tumor suppressor expression and function that drive oncogenic transformation; The role of microRNAs as tumor suppressors and oncogenes; Identification and characterization of solid tumor stem cells; biology of progenitor cells that may be the target of oncogenic transformation in solid tumors; Mechanisms of overcoming senescence in the context of oncogenesis and mechanisms of cellular immortalization as a prerequisite for oncogenic transformation; Relationship between cellular aging and cancer; the role of developmental genes and the effect of perturbations in cellular differentiation in cancer.
Cellular Transformation: Signal Transduction (Rihab Yassin)
Alterations in signal transduction pathways that may modulate or lead to oncogenic transformation; functional and molecular characterization of signal transduction pathways/networks relating to cell growth, survival and death in the context of transformation; Signaling by cell surface receptors, cytokines, protein kinases, phosphatases, lipids or other molecules and their interactions in transformation, including the analysis of the composition, formation, and functioning of signaling complexes and mediators; membrane-derived lipid mediators and their role in early transformation and The role of cytokines and associated inflammatory signaling cascades in oncogenic transformation and promoting cell survival, for example the activation of the NFkB cascade, through the TNF receptor super family or Toll-like receptors.
Biospecimen Resources to Support Studies in Cancer Biology: (Rihab Yassin)
Resources that collect, store, process, and disseminate human biological specimens, including nucleic acids and tissue arrays, and associated data to investigators who study human cancer biology, particularly early events in oncogenic transformation. Development of processes to comply with human subjects research regulation and improve best practices are also supported.
Emerging Research Topics of Particular Interest:
·Nutrient-sensing
and metabolic balance in cancer cells
