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Sabrina Spencer

Personal Web Page

http://www.mit.edu/~spencers/

Education

B.S. in Biology & B.A. in French Literature, The George Washington University
M.S. in Human Genetics, University of Michigan
Ph.D. in Computational and Systems Biology, MIT

Research

Cells in isogenic populations display significant variability in their fate after stimulation with TNF-family ligands; many cells die at different times, and some cells do not die at all. Cell pedigree analysis reveals that there is an important deterministic component to death time variability, i.e. one that arises from distributed initial conditions among cells. Using live-cell microscopy with fluorescent reporters, I have dissected the molecular events underlying cell-to-cell variability and have found that the interface of caspase-8 activity and mitochondrial permeabilization is of particular importance. Combining these data with a formalized differential equation model of the TRAIL signaling pathway, I identify unexpected complexities in the kinetic regulation of mitochondrial permeabilization.

Publications

Niepel M, Spencer SL, Sorger PK. Non-genetic cell-to-cell variability and the consequences for pharmacology. Curr Opin Chem Biol. 2009 Dec;13(5-6):556-61.

Kim KA, Spencer SL, Albeck JG, Burke JM, Sorger PK, Gaudet S, Kim DH. Systematic calibration of a cell signaling network model. BMC Bioinformatics. 2010 Apr 23;11(1):202.

Spencer S.L.*, Gaudet S.*, Albeck J.G., Burke J.M., Sorger P.K. (2009) Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature 459, 428-432.

Pepper, J.W., Findlay, C.S., Kassen, R., Spencer, S.L., Maley, C.C. (2009) Cancer research meets evolutionary biology. Evolutionary Applications 2, 62-70.

Albeck J.G.*, Burke J.M.*, Spencer S.L., Lauffenburger D.A., Sorger P.K. (2008) Modeling a snap-action, variable-delay switch controlling extrinsic cell death. PLoS Biology 6(12): e299.

Spencer S.L.*, Gerety R.A.*, Pienta K.J., Forrest S. (2006) Modeling Somatic Evolution in Tumorigenesis. PLoS Computational Biology 2(8): e108.

In Preparation

Gaudet S.*, Spencer S.L.*, Chen W., Sorger P.K. Computational analysis of cell-to-cell variability in apoptosis (in preparation).

Flusberg D., Spencer S.L., Sorger P.K. Non-genetic determinants of cellular sensitivity to TRAIL-mediated apoptosis in single cells (in preparation).

(* indicates equal contribution)

Collaborators

John Albeck, Suzanne Gaudet, Deborah Flusberg, John Burke