Research

Biochemistry: signaling, transcription, computational network; stress and immune responses, apoptosis, proliferation

Mammalian cells respond rapidly to environmental stresses, pathogens and inter-cellular signals in order to protect themselves, minimize damage to the organism, and coordinate an immune response. Each signal activates the expression of a specific set of genes, utilizing signaling pathways in the cell that not only transmit the signal to the nucleus but process the information contained within the signal.

Our interest focuses on the IkB/NF-kB signaling pathway, which plays critical roles in inflammation, immunity, stress responses and many human diseases such as cancer, immunodeficiencies, and arthritis. The two gene families comprise a total of 11 homologous proteins. Gene knockout studies in mice have shown that signaling via this pathway can have very diverse, even opposite physiological effects, e.g. cell proliferation vs senescence, survival vs apoptosis, pro- vs anti-inflammatory. The goal of our research program is to elucidate signal processing mechanisms within the IkB/NF-kB pathway and the specificity of its components as they relate to the stimulus-specific, gene-specific, and cell type-specific responses underlying diverse physiological functions.

In our research we combine genetics (a comprehensive panel of IkB/NF-kB gene knockout mice and derived cells), biochemistry (track signaling intermediates in the cells), molecular biology (alter the balance of signal transducers, utilize marker genes, genome wide expression studies) to develop a computational model of IkB/NF-kB signaling. Computational simulations lead to predictions about natural and disease processes that are then tested experimentally. We hope not only to contribute generalizable insights into cellular signaling but also to provide leads for therapeutic strategies in a number of human diseases.