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‣ Fission Yeast Germinal Center (GC) Kinase Ppk11 Interacts with Pmo25 and Plays an Auxiliary Role in Concert with the Morphogenesis Orb6 Network (MOR) in Cell Morphogenesis*
‣ Cell Encapsulation in Sub-mm Sized Gel Modules Using Replica Molding
‣ IQGAP1-Dependent Signaling Pathway Regulates Endothelial Cell Proliferation and Angiogenesis
‣ miRNA-720 Controls Stem Cell Phenotype, Proliferation and Differentiation of Human Dental Pulp Cells
‣ Disrupting the Interaction between Retinoblastoma Protein and Raf-1 Leads to Defects in Progenitor Cell Proliferation and Survival during Early Inner Ear Development
‣ FAS-Based Cell Depletion Facilitates the Selective Isolation of Mouse Induced Pluripotent Stem Cells
‣ Genetic Deletion of SEPT7 Reveals a Cell Type-Specific Role of Septins in Microtubule Destabilization for the Completion of Cytokinesis
‣ Mechanisms of Stem Cell Maintenance and Cell Differentiation in the Intestinal Epithelium
‣ Crosstalk between E2F3 and p19ARF/p53 in the regulation of cell cycle progression and tumorigenesis
‣ Quantitative analysis of the T cell receptor signaling network in response to altered peptide ligands
‣ 7.012 Introduction to Biology, Fall 2001; Introduction to Biology
‣ The regulation of programmed and pathological cell death in C. elegans
‣ Evolutionary cell biology: two origins, one objective
‣ Multi-Scale Imaging and Informatics Pipeline for In Situ Pluripotent Stem Cell Analysis
‣ Multi-step loading of human minichromosome maintenance proteins in live human cells; Running title: Maximal loading of MCM2/4 in late G1
‣ Mapping Differentiation under Mixed Culture Conditions Reveals a Tunable Continuum of T Cell Fates
‣ Cancer Cell Motility: Optimizing Spatial Search Strategies
‣ Computational methods for multi-omic models of cell metabolism and their importance for theoretical computer science
‣ Quantitative analysis of cellular networks: cell cycle entry
Cellular dynamics arise from intricate interactions among diverse components, such as metabolites, RNAs, and proteins. An in-depth understanding of these interactions requires an integrated approach to the investigation of biological systems. This task can benefit from a combination of mathematical modeling and experimental validations, which is becoming increasingly indispensable for basic and applied biological research.
Utilizing a combination of modeling and experimentation, we investigate mammalian cell cycle entry. We begin our investigation by making predictions with a mathematical model, which is constructed based on the current knowledge of biology. To test these predictions, we develop experimental platforms for validations, which in turn can be used to further refine the model. Such iteration of model predictions and experimental validations has allowed us to gain an in-depth understanding of the cell cycle entry dynamics.
In this dissertation, we have focused on the Myc-Rb-E2F signaling pathway and its associated pathways, dysregulation of which is associated with virtually all cancers. Our analyses of these signaling pathways provide insights into three questions in biology: 1) regulation of the restriction point (R-point) in cell cycle entry...
‣ Defining Roles for Cyclin Dependent Kinases and a Transcriptional Oscillator in the Organization of Cell-Cycle Events
The cell cycle is a series of ordered events that culminates in a single cell dividing into two daughter cells. These events must be properly coordinated to ensure the faithful passage of genetic material. How cell cycle events are carried out accurately remains a fundamental question in cell biology. In this dissertation, I investigate mechanisms orchestrating cell-cycle events in the yeast,
Cyclin dependent kinase (CDK) activity is thought to both form the fundamental cell-cycle oscillator and act as an effector of that oscillator, regulating cell-cycle events. By measuring transcript dynamics over time in cells lacking all CDK activity, I show that transcriptional oscillations are not dependent on CDK activity. This data indicates that CDKs do not form the underlying cell-cycle oscillator. I propose a model in which a transcription factor network rather than CDK activity forms the cell-cycle oscillator. In this model, CDKs are activated by the periodic transcription of cyclin genes and feedback on the network increasing the robustness of network oscillations in addition to regulating cell-cycle events.
I also investigate CDK-dependent and -independent mechanism regulating the duplication of the yeast centrosome...