Current Research Activities
Cells have evolved to contain a suite of homeostatic mechanisms to maintain a relatively stable intracellular milieu in the face of exogenous stress including chemical perturbations. Hence it is important that the toxicity of environmental chemicals and pollutants be studied in the context cellular homeostasis and adaptation. A focus of work at the Center is to understand how the molecular circuits underlying cellular homeostasis are organized, and how they function as highly nonlinear dynamical systems. Such an understanding will provide valuable qualitative and quantitative information for the shape of dose response curves at both the cellular and tissue levels.
Oxidative stress and DNA damage and repair responses are active areas of research at the Center. In contrast to homeostasis, under some environmental conditions cells undergo a discrete, often irreversible, change in phenotypic state, such as proliferation, differentiation, apoptosis. These processes are often driven by switching of transcriptional networks containing positive or double-negative feedback loops between mutually exclusive attractor states. The Center has been developing deterministic and stochastic models of the gene networks that regulate terminal differentiation of B lymphocytes to antibody-secreting plasma cells, and providing insight into the mechanisms by which environmental contaminant dioxin disrupts this process. Recently, the Center has begun to integrate p53-mediated molecular networks underlying genome homeostasis, cell cycle arrest and apoptosis to inform dose response relationship for mutagenesis and carcinogenesis.