John Albeck

Biosketch

B.A. Biological Sciences, Cornell University, 2000

Ph.D. candidate, Department of Biology, MIT, current

Primary Collaborators

John Burke, Lauffenburger lab, MIT

Suzanne Gaudet, Sorger lab, MIT

Kevin Janes, Lauffenburger lab, MIT

Bree Aldridge, Sorger lab, MIT

Sabrina Spencer, Sorger lab, MIT

CDP Publications

Janes K.A., Albeck J.G., Peng L.X., Sorger P.K., Lauffenburger D.A., Yaffe M.B., (2003) "A High-throughput quantitative multiplex kinase assay for monitoring information flow in signaling networks: Application to sepsis-apoptosis." Mol. Cell. Proteomics, 7:463-473.

Janes K.A., Kelly J.R., Gaudet S., Albeck J.A., Sorger P.K., and Lauffenburger D.A., (2004) " Cue-signal-response analysis of the TNF-induced apoptosis by partial least squares regression of dynamic multivariate data", J. Comput. Biol., 11: 544-61.

Gaudet S., Janes K.A., Albeck J.G., Pace E.A., Lauffenburger D.A., and Sorger P.K. (2005) "A compendium of signals and responses triggered by prodeath and prosurvival cytokines.", Mol. Cell. Proteomics, 10: 1569-1590.

Janes, K.A., Gaudet, S., Albeck, J.G., Nielsen, U.B., Lauffenburger, D.A., and Sorger P.K. (2005). "Autocrine crosstalk in the response of human cells to apoptotic and mitogenic stimuli." Submitted.

Janes K.A., Albeck J.G., Gaudet S., Sorger P.K., Lauffenburger D.A., and Yaffe M.B. (2005). "A Systems Model of Signaling Identifies a Molecular Basis Set that Predicts Cytokine-Induced Apoptosis." Science, in press.

Research Focus

Cells are constantly responding to external signals that tell the cell how to behave: when to divide, how fast to grow, whether to die or differentiate, and so on. Many of these behaviors, such as cell death or division, are binary – the cell must decide on one of two outcomes. But how are these binary decisions made when biochemical events are implicitly capable of partial activation? For example, caspase-3 is a key effector caspase – a protease that, once activated, induces apoptosis (programmed cell death) by cleaving important cellular substrates, including cytoskeletal and DNA repair proteins. In a healthy cell, there are approximately 20,000 copies of inactive caspase-3, which are available to be activated in response to pro-apoptotic stimuli. Usually, in response to such stimuli, a large number of these copies of caspase-3 will become activated and the cell will rapidly enter into apoptosis. But how does the cell prevent activation of just a few of these copies? A situation like this could be very dangerous, because it could lead to damage to the DNA or other cellular structures without actually killing the cell. To prevent such errant behaviors, the network of proteins regulating caspase-3 activation must be set up to act as an all-or-none switch. My main research project is to understand what parts of the caspase-3 regulatory network are necessary for the all-or-none switch. In order to do this, we track the behavior of single cells using live-cell microscopy and flow cytometry; at the same time, we use siRNA to remove specific proteins in the network, allowing us to observe the effect of each removal on the ability of cells to respond to pro-apoptotic stimuli in an all-or-none manner. Using this information, we have developed a mathematical model of caspase-3 regulation that provides insight into what makes caspase activation all-or-none.