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Modeling Cellular Processes The emphasis of my work since 1999 has been on the modeling of
cellular processes that I think are most relevant to cancer development.
By adopting what molecular biologists think are the most important
molecular pathways involved in a given cellular physiological process, one
has a reduced network that could be investigated further. Of course,
this hypothesis-driven modeling approach has its pitfalls, so I am now very
keen at finding ways to extract network models from pathways databases.
The following are the major topics that we have published on: Cell Cycle Checkpoints. These are surveillance mechanisms that arrest or slow down cell cycle progression if certain requirements for transition to the next phase are not met. Links to publications: PD cycles & cell cycle checkpoints, Kinetic origins of the restriction point , G2 DNA damage checkpoint. erratum. Coupling
between Apoptosis & the Cell Cycle. One expects that the decisions to proliferate or
die are coordinated. Links to publications: cell cycle and apoptosis (Aguda &
Algar), cell
cycle and apoptosis (Craciun, Aguda & Friedman), cell cycle and apoptosis (Aguda, Yio,
Ng). Cell Survival Pathways vs Apoptosis. Biologists say that the 'death state' is the default cellular state. We are hypothesizing then that there must be critical and controllable sets of nexus of survival and death signaling pathways. Links to publications: Akt vs p53 (Wee & Aguda) Apoptosis. This also referred to as 'programmed cell death'. Modeling activation of caspases; Creating and analyzing a modular model of apoptosis: MBI 2007 Grad Summer Sch Project, Students' Presentation. Signaling
pathways. Links to
publications: G1-S pathways (2001), map kinase signaling (2004) Modeling Specific Biomedical Systems Inflammation. We have current collaboration with the Agarwal Lab on inflammation and
exercise. Recent work: Modeling
NF-kB signaling , Modeling cyclic mechanical stress and NF-kB
oscillations, Modeling transition to inflammation, most recent bistable
model here later. Vascular
disease. Endothelium
aging and maintenance. Link to publications: Wang, Aguda & Friedman (2007). Breast
Cancer. We just started
our collaboration with Clay Marsh's group at the Critical Care Center
of the Pathways Databases & Network Analysis From Pathways Databases to Network Models. We should be exploiting the huge amounts of information in databases to generate realistic mathematical models of cellular processes and physiology. Links to publications: PLoS Comp Biol ( 2007), Rev Comp Chem (2005) Network Analysis. We are also interested in theoretical and computational tools for analyzing complex biological networks. Links to some older publications: bistability in reaction networks (1987), dynamic elements in the WR network (1988), dynamic elements in the PO network (1989), emergent behavior of couple enzyme networks (1996) |
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